The association between renal cell carcinoma (RCC) risk and family history of cancer has not been examined with an adequate number of African Americans (AAs).In a population-based case–control study, unconditional logistic regression was used to calculate the association between RCC risk and a family history of cancer among 1217 RCC cases and 1235 controls.Increased RCC risk was shown for subjects with at least one first-degree relative with kidney cancer . No differences in risk were observed when analyses were stratified by race. For Caucasians, excess risk was observed among those reporting a sibling with kidney cancer, whereas for AAs, increased risk occurred among subjects reporting either a sibling or parent affected with the disease. A family history of non-renal cancers, and those related to smoking or to the von Hippel–Lindau syndrome, revealed no association with RCC risk.The RCC risk associated with a family history of kidney cancer is similar among Caucasians and AAs. In the United States, malignant tumours of the kidney account for nearly 4% of cancer diagnoses and 2% of cancer deaths . Since 1The aetiology of RCC is complex, with both environmental and hereditary components suspected to have a role. Smoking, obesity, and hypertension are primary risk factors that may explain half of all RCC diagnoses in the United States . RCC risDespite the racial disparity in RCC incidence, the numbers of AAs studied have been insufficient to examine their risk separately. In a recently completed population-based case–control study with a relatively large number of AA subjects, we examined whether RCC risk was elevated among participants with a history of cancer among first-degree relatives, and whether risk varied by race.This population-based case–control study was conducted in Chicago, IL, and in Detroit, MI. Cases were resident Caucasian and AA men and women, aged 20–79 years, newly diagnosed with RCC in Chicago from 1 January 2003 through to 31 December 2003 and in Detroit from 1 February 2002 through to 31 January 2007 for AAs and through to 31 July 2006 for Caucasians. All cases had histologically confirmed adenocarcinoma of the kidney (ICD-O C64). Controls selected from the general population were frequency matched to cases on age, race, sex, and study centre. Controls aged 65–79 years were identified from files of the Centers for Medicare and Medicaid Services, and controls under the age of 65 years were identified from the Department of Motor Vehicle (DMV) records. A sampling strategy was designed to increase the number of AA participants used for analyses. All AA cases were recruited, whereas some strata (age–race–sex combinations) of Caucasian cases were subsampled. Controls were frequency matched to cases at a 2 : 1 ratio for AAs and at a 1 : 1 ratio for Caucasians. As information on race was unavailable from DMV records, this hampered our ability to frequency match controls to cases among those 20–64 years of age. Therefore, we used the racial density of the census block group (according to the 2000 census), in which each control resided to serve as a surrogate for race for the purposes of sampling. We oversampled people living in high-density AA areas to help achieve the targeted matching ratios for AAs.Of 1918 eligible cases identified, 171 died before contact or interview, 92 could not be located with the available contact information, 21 moved out of the area, and the physicians of 63 cases refused permission to contact their patients. Among the remaining 1571 cases we sought to enrol, 221 declined participation and 133 were not interviewed because of serious illness, impairment, or failure to respond to multiple attempts to contact. Thus, 1217 cases (77.5% of those we attempted to recruit) participated in the study. Of 2718 presumed eligible controls, 41 died before contact or interview, 345 could not be located with the available contact information, and 63 had moved out of the region. Among the 2269 controls we attempted to recruit, 677 declined to participate and 357 were not interviewed because of serious illness, impairment, or failure to respond to multiple attempts to contact. Thus, 1235 eligible controls (54.4% of those we attempted to recruit) participated. Institutional review board approvals were obtained from all participating study centres and informed written consent was obtained from all participants.Trained interviewers were administered an in-home, computer-assisted personal interview, in which detailed information was collected on demographics, smoking history, medical and medication history, diet, occupation, and family history of cancer. Information on family history of cancer was collected for all first-degree relatives , including cancer site and age at diagnosis. For analytical purposes, a set of sample weights were developed to reduce the potential for bias arising from differential sampling rates for controls and cases, from survey non-response, and from deficiencies in the coverage of the population at risk by the files of the DMV and Centers for Medicare and Medicaid Services to select controls. For controls, their sample weights also include a poststratification adjustment so that the weighted distribution of controls across the matching variables matches the weighted distribution of cases in an exact manner. In addition to being consistent with the objectives of frequency matching, this poststratification adjustment reduces the variability of the weights compared with not using this adjustment . Unconditional logistic regression models using poststratified weights were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) associated with a family history of kidney cancer and a family history of non-renal cancers, using subjects who did not have any family history of cancer as the reference group. The jackknife replicate weight method was used to estimate s.e. , sex, race, study centre, education level, hypertension history , family size (defined as number of siblings and number of offspring), smoking status, and body mass index. Unweighted unconditional logistic regression analyses and tests for interactions comparing regression models with and without interaction terms were also calculated, in which results were similar to that of the weighted analysis (data not shown). All analyses were conducted with STATA software version 10.1 . Cases were more likely to have a lower education level than controls. Similar distributions of characteristics were observed when analyses were stratified by race.Overall, cases and controls were comparable in sex and age distributions . As expeP-interaction=0.19). A family history of non-renal cancers among first-degree relatives was not associated with RCC risk, regardless of whether family history was defined by relative type or stratified by race.A significant elevation in risk is shown in RCC risk was comparable whether one  or more than one  first-degree relative was reported to have been diagnosed with kidney cancer. The findings were similar when family history of non-renal cancers was reported in one  compared with more than one  first-degree relative. No meaningful differences in risk were observed with regard to relative type or race (data not shown).Because the von Hippel–Lindau syndrome is commonly linked to inherited RCC, we examined the relationship between RCC risk and a family history of several cancers that have been reported in families with this syndrome  . No assoThis study confirms an association between RCC risk and a family history of kidney cancer and, for the first time, shows that such risk is comparable among Caucasians and AAs in the United States. Among Caucasians, the excess risk was observed mainly in individuals who reported having a sibling with kidney cancer; among AAs, excess risk was seen whether the affected relative was a sibling or a parent.Increased risk of renal cancer has been associated with a family history of kidney cancer in most previous case–control (VHL) tumour-suppressor gene on chromosome 3p, which is associated exclusively with the clear cell histological subtype ; however, the weighting strategies used in this study allowed for analyses that were more robust to non-response and the power for stratified analyses was limited. We did not verify the self-reported history of kidney cancer among first-degree relatives, and recall may have been more accurate among cases than among controls. However, we believe this to be unlikely as no association with an increasing number of affected first-degree relatives with kidney cancer was observed.This study finds that family history of kidney cancer among first-degree relatives is associated with a significantly increased RCC risk, and that risk is similar in Caucasians and AAs.


From 1976 to 2004, we followed 71 751 participants of the Nurses' Health Study and identified 676 invasive endometrial cancer cases. Birthweight, assessed in 1992, was not associated with the incidence of endometrial cancer. No effect modification by menopausal status was observed, but statistical power to detect an interaction was limited. Endometrial cancer is the commonest invasive gynecologic cancer in women in the United States, with nearly 40 000 new cases diagnosed each year . BirthweUsing data from 28 years of follow-up of 71 751 women participating in the Nurses' Health Study (NHS), we examined the association between birthweight and incidence of endometrial cancer later in life.in situ or invasive endometrial cancer, had a hysterectomy, died or were lost to follow-up.The NHS was established in 1976, when 121 700 married registered nurses age 30–55 years replied to a baseline questionnaire and received questionnaires biennially by mail to update information on demographic, anthropometric, and life style factors, and on newly diagnosed disease. For the current analysis, we excluded women with missing birthweight data, prevalent cases of endometrial or other cancers, and women with hysterectomy at baseline. During follow-up, women were censored if they reported recently diagnosed In 1992, we asked participants to report their own birthweight with the following options: <2.500, 2500–<3182, 3182–<3863, 3863–<4545, ⩾4545 g. On each biennial questionnaire, participants were asked whether they had been newly diagnosed with endometrial cancer during the previous 2 years. The National Death Index was also routinely searched for deaths among women who did not respond to the questionnaires. For endometrial cancers reported by women or their next of kin for those who had died, permission was requested to review the relevant medical records. Study physicians reviewed all medical records and pathological reports to confirm their diagnosis. Cases included in this study were invasive epithelial endometrial cancers with stage greater than IA in the FIGO staging system.At baseline and during follow-up, we inquired about a variety of personal characteristics including reproductive and life style factors, many being risk factors for endometrial cancer. Information on age, age at menarche, age at first birth and height was obtained at baseline in 1976. Other early life exposures including premature birth (2+ weeks premature) and duration of having been breast-fed were assessed in 1992, and birth order was queried in 2004. Weight at age 18 was assessed in 1980. Somatotype at age 5 and 10 was assessed in 1988 by asking participants to choose from nine diagrams that best depicted their figure outline at each age. Maternal vital status and family history of endometrial cancer was asked in 1996. Other covariates were inquired and updated during follow-up.The association between birthweight and incidence of endometrial cancer was analysed using a Cox proportional hazards model. Three covariate-adjusted models were pursued. In the first model (model I), we adjusted only for family history of endometrial cancer and other early life exposures including birth order, duration of being breast-fed and premature birth, in addition to age. In the second (model II), we also included other established or potential risk factors for endometrial cancer. In the third (model III), we additionally adjusted for anthropometric factors, including somatotype at ages 5 and 10, BMI at age 18, and current BMI. Though covariate-adjusted models II and III have better goodness of fit due to additional adjustment for potential risk factors of endometrial cancer, these factors are subsequent to birthweight and could conceivably mediate the effect of birthweight on endometrial cancer risk. Therefore, adjusted model I would be the preferred model to estimate the overall effect of birthweight.As birthweight was not assessed until 1992, we conducted a sensitivity analysis restricting follow-up to 1992–2004 and compared the results with the primary analysis using the entire follow-up. We also evaluated potential effect modification by menopausal status, anthropometric factors, and other early-life exposures.During 1 678 702 person-years of follow-up among 71 751 women, 676 cases of incident endometrial cancer were confirmed. Based on the eligible person-years, the follow-up rate for the entire cohort in our study from 1976 to 2004 was 88%. Women with higher birthweight were less likely to have been prematurely delivered and to be the first born of their mother, were more likely breastfed, more likely to have ever smoked, and were slightly taller, than women with lower birthweight .g, respectively, as compared to ⩾3863 g, P for trend=0.52) in the age-adjusted analysis (vs 1992–2004) (P=0.80).Birthweight was not associated with endometrial cancer (HR (95% CI)=1.14 (0.83–1.57), 1.10 (0.85–1.42), 1.14  for a birthweight of <2500, 2500–<3182, 3182–<3863 analysis . Resultsanalysis . When reanalysis . A test P=0.41); however, statistical power was limited for premenopausal cases ) (g to that in women >3000 g)  (The statistical power of this study would allow us to detect a modest association, if it exists. Many risk factors for endometrial cancer and other early life exposures were assessed and accounted for in the analysis. Though birthweight was queried 16 years after the start of follow-up, when compared with the analysis restricted to prospective follow-up, results including the entire follow-up of 28 years did not differ appreciably. We have previously compared self-reported birthweight with data derived from birth certificates and found self-reported birthweight to be highly reliable (Current research suggests that women can decrease their risk of endometrial cancer mainly through maintaining normal weight, modifying lifestyle, and optimal use of oral contraceptives and postmenopausal hormones (


BRCA1/2 mutation-positive and -negative women from an IRB-approved research study.Ductal lavage (DL) has been proposed as a minimally-invasive, well-tolerated tool for obtaining breast epithelial cells for cytological evaluation of breast cancer risk. We report DL tolerability in BRCA1/2 mutation-positive, 26 mutation-negative and 3 mutation unknown women underwent mammography, breast MRI and DL. Psychological well-being and perceptions of pain were obtained before and after DL, and compared with pain experienced during other screening procedures.165 anticipated and experienced discomfort rating for DL, 47 and 48 (0–100), were significantly higher (p < 0.01) than the anticipated and experienced discomfort of mammogram (38 and 34), MRI (36 and 25) or nipple aspiration (42 and 27). Women with greater pre-existing emotional distress experienced more DL-related discomfort than they anticipated. Women reporting DL-related pain as worse than expected were nearly three times more likely to refuse subsequent DL than those reporting it as the same or better than expected. Twenty-five percent of participants refused repeat DL at first annual follow-up.The average more uncomfortable than other procedures used in breast cancer screening. Higher underlying psychological distress was associated with decreased DL tolerability.DL was anticipated to be and experienced as  Ductal lavage (DL) is a method of collecting breast epithelial cells from the lining of the breast duct by means of a small-gauge catheter inserted into a ductal orifice on the nipple to permit direct access to exfoliated breast duct epithelial cells. Information gained from DL might improve early breast cancer detection, facilitate breast cancer risk assessment, and yield novel reagents for developing biomarkers and intermediate end-points in chemoprevention trials . EpithelBRCA1/2 mutation carriers, and even fewer who were unaffected BRCA1/2 mutation carriers, were included in these reports [There are several reports of DL-related pain in women at high risk of breast cancer, but few women who were known to be  reports ,18,19. V reports ,18,19 or reports  and a foEmotional distress might influence DL tolerability, since previous general population studies have suggested that women reporting higher levels of pre-procedure distress experience greater mammogram-related discomfort -24. ImpoBRCA1 or BRCA2 mutations. BRCA1/2 mutation carriers have an estimated lifetime risk of breast cancer between 45%–82% [The National Cancer Institute Clinical Genetics Branch Breast Imaging Study  is a four-year, prospective cohort study of 200 women from families with known  45%–82% -29. Chem 45%–82% -32 and a 45%–82% -38. The and had a known deleterious BRCA1/2 mutation, or were first- or second-degree relatives of BRCA1/2 mutation carriers, or were first- or second-degree relatives of individuals with BRCA-associated cancers in BRCA1/2 mutation-positive families. Exclusion criteria included: pregnancy or lactation within 6 months of enrollment, abnormal CA-125, bilateral breast cancer, ovarian cancer or breast cancer (Stage IIB or greater), unless relapse-free for 5 years prior to enrollment. Participants with a personal history of DCIS, or Stages I/II breast cancer were eligible, provided that ≥ 6 months had elapsed since completing primary therapy. Other exclusion criteria included: a personal history of other invasive cancer (except for non-melanoma skin cancer), unless relapse-free for 5 years prior to enrollment; prior bilateral mastectomy; bilateral breast irradiation; weight > 136 kilograms; and gadolinium allergy. DL was not performed on participants with allergy to lidocaine or bupivacaine; peri-areolar or other breast surgery which might disrupt the ductal systems of the breast; a breast implant or prior silicone injections in the breast; and active infection or inflammation in the breast to be studied.Eligible women were between ages 25–56, p < 0.05). The final study sample included 156 (194 – 38) participants.This analysis includes data from 194 women who were enrolled during the period June 2002 through May 2006. Reasons for not performing DL included physician cancellation (n = 13), being ineligible (n = 4), and refusing (n = 5). Participants who did not attend both pre- and post-DL clinic visits were excluded from the analysis (n = 38). Excluded women were similar to those analyzed relative to procedure tolerability ratings, sociodemographic variables, and other study outcomes, except that excluded women were more likely to have a history of breast cancer and to have had NAF obtained during DL (SD = 8.6); 90% had attained > high school education. Eighty-five percent were BRCA1/2 mutation-positive, and 10% reported prior breast cancer. Ninety-seven percent of subjects were white, a proportion reflecting the Clinical Genetics Branch referral pattern.Mean participant age was 39.4  and various healthcare providers , primarily in response to mailed recruitment letters, or were self-referred from our BIS website 16/156 (10%) . The provia the lavage catheter. The location of each lavaged duct was recorded by threading a blue suture into the duct orifice, photographing the breast  applied to the nipple/areola 60 minutes prior to the procedure, was provided to all DL participants. The nipple/areolar complex surface was gently probed with a micro dilator tip prior to DL, to confirm adequate anesthesia. In women who reported probing-related pain, additional topical anesthesia and/or subcutaneous injections of lidocaine around the base of the nipple were administered. Nipple aspiration was performed to identify all fluid-yielding ducts. We attempted to identify and cannulate all visible ducts, regardless of NAF status . After successful catheter insertion, 3–5 mL of 1% lidocaine was infused, followed by 20 mL of sterile normal saline, in 5 mL aliquots. After each aliquot was infused, the breast was massaged and fluid collected Three clinicians performed the BIS DL procedures: JTL, adult nurse practitioner, RAG, medical oncologist and LR, surgical oncologist. The clinicians were trained to perform ductal lavage using the technique described by Dooley et al . Most frFour indices of breast screening procedure tolerability were used.anticipated discomfort before undergoing any of the screening procedures, and on Day 2 participants rated experienced discomfort after completing all screening procedures.First, women rated each procedure's  discomfort on a 0 to 100 scale, with 100 indicating the worst discomfort imaginable. On Day 1, participants rated In addition, participants were asked on Day 2 whether discomfort associated with each screening procedure was worse, the same as, or better than expected.Women were queried whether the DL-associated discomfort was worse, the same, or better than 7 common medical procedures , andParticipants characterized pain quality by selecting between the descriptors burning, aching, radiating, sharp, dull, fullness, or tingling.on that day.The Brief Symptom Inventory 18 (BSI 18) Global Severity Index (GSI) was used to quantify overall psychological distress levels. The BSI 18 has been widely used to assess distress in medical oncology settings, with good reliability and validity . It was Women were asked to return for follow-up DL screening one year after initial screening. Participants either completed follow-up DL, cancelled their appointment, refused follow-up DL, or had not received follow-up DL at the time of the current analysis for another reason .BRCA1/BRCA2 mutation status in relation to DL tolerability; therefore, these variables were included in the present study [Prior reports have examined age, presence of NAF, history of breast cancer and nt study ,18,19.t-tests, and 2) to examine continuous ratings of experienced DL discomfort in relation to study variables  using bivariate correlation (r), independent samples t-tests, or ANOVA. Multivariate analyses used linear and logistic regression to model continuous ratings of anticipated and experienced DL discomfort, and to estimate the odds of refusing follow-up DL. Some participants declined one or more of the screening procedures; therefore, sample size is reported for each analysis presented in the Tables.Data analyses were conducted using SPSS Version 15.0 (2006). Bivariate analyses were used to 1) compare continuous ratings of both anticipated and experienced procedure discomfort (0–100) between DL and other breast screening procedures, using paired p < 0.05); mammogram and DL ratings of experienced discomfort did not differ significantly from participants' anticipation (Table p < 0.01), suggesting that in this cohort, DL was tolerated significantly less well than other breast screening procedures. The majority of women described the discomfort associated with DL as "sharp" (78%) or "burning" (52%). The majority of women also reported that DL discomfort was the same as/worse than discomfort associated with a Novocaine injection (65%), a blood draw (61%), a pelvic (59%) or rectal examination (64%).MRI and NAF were significantly less painful than anticipated . Higher levels of distress were associated with significantly higher ratings of experienced DL discomfort (p < 0.05), with women who refused follow-up DL reporting the highest experienced DL discomfort (p < 0.01).Bivariate analyses Table  indicateBRCA1/2 mutation status was not included in the multivariate models.Multivariate methods were used to examine anticipated and experienced DL discomfort ratings Table , and oddp < 0.05) in Step 1. Adding anticipated discomfort to the model in Step 2 did not change the results of Step 1; anticipated DL discomfort was not associated with experienced DL discomfort (p = 0.48), although the effect for GSI became marginally significant (p = 0.08) when anticipated discomfort was added to the model.None of the study variables were associated with ratings of anticipated DL discomfort Table . For expp = 0.06). Higher scores on the GSI  were associated with higher odds of refusing follow-up DL . Women who reported that DL discomfort was worse than they expected it to be (34% of the study sample) were more than three times more likely to refuse follow-up DL  than those reporting DL discomfort as the same, or better than expected (66% of participants). Results were consistent in a second regression model in which we substituted the continuous experienced DL discomfort measure (0–100) for the categorical discomfort classifier. In the continuous model, the odds of refusing follow-up DL increased by 5% with every 1-point increase in experienced DL discomfort ratings .We used multivariate logistic regression to model the odds of refusing follow-up DL (24% of participating women refused)  were more likely to experience greater DL-related discomfort than women with lower distress ratings.Several findings have direct impact on the management of women undergoing DL. First, it seems apparent that for most women undergoing DL, the current anesthesia protocol is inadequate. We were able to achieve acceptable anesthesia at the nipple surface, but passing the catheter through the constricted ductal sphincter was an important source of procedure-related pain. Local anesthesia alone did not relax this sphincter, and nor did using topical nitro-paste (for smooth muscle relaxation) make a significant difference.It is somewhat surprising that younger women and women without a prior history of breast cancer had similar reports of discomfort with DL when compared with older women and women with a prior history of breast cancer. Compared with other groups who have reported on DL tolerability ,13,18,19in situ, 199 were high risk due to a Gail Model risk of ≥ 1.7, 4 were not at high risk of breast cancer, and only 3 were BRCA1/2 mutation carriers. A median pain score of 28 mm on a 0–100 mm visual analogue scale which was administered immediately after DL was reported (1). However, 28% of subjects underwent the procedure in the operating room under general anesthesia and less than one percent of the subjects were cancer-unaffected, known BRCA1/2 mutation carriers. No comparison of pain scores between subjects who received general anesthesia versus those who did not was reported.Pain associated with DL has been evaluated by several groups ,13,18,19BRCA1/2 mutations. A similar rating of 2.8/10 was reported immediately after DL, and DL pain was described as similar to the pain experienced with mammography. As with the previous study (1), more than 50% of participants were breast cancer survivors. Neither group reported whether differences existed in measures of pain between women with a prior history of breast cancer and unaffected women. It is possible that women who are breast cancer survivors experience pain differently from women without a prior history of breast cancer. Neither group  reported the acceptance rate of future DL in their study populations.Mitchell et al. (20) employed a visual analogue scale (range 0–10) to record measurements of pain in 52 women with BRCA1/2 mutation carriers rated DL-related pain on a scale of 1 to 3 , and compared their experience with DL to breast MRI on a scale of 1 to 5 . BRCA1/2 mutation carrier participants more often rated DL as maximally uncomfortable versus MRI or mammogram, and the maximal discomfort ratings for DL vs. mammogram and MRI combined reached statistical significance (P = 0.04). There was no difference in reports of pain between breast cancer survivors and unaffected women; however, the sample size was small , and mutation status was not reported. Future acceptance of DL was not reported in this study population.DL tolerability was reported in a retrospective study in women at high risk of breast cancer who had been evaluated as part of a breast cancer screening study . Twenty-BRCA1/2 (n = 2), a personal history of abnormal breast biopsies  or a prior history of breast cancer  was found to be less than ideal [BRCA1/2 mutation carriers within this group of women to determine whether mutation carriers differ in measures of pain from other women at high risk of breast cancer.The reliability and acceptability of DL in 69 women at high risk of breast cancer due to Gail Model score ≥ l.66 (n = 38), a family history of breast cancer (n = 53), the presence of a an ideal . A visuaEmotional distress might influence measures of DL pain and acceptance, since previous general population studies have suggested that women describing higher levels of emotional distress report greater mammogram-related discomfort -24. FurtBRCA1/2 carrier mutation status to undergo annual DL. It is also the largest group of unaffected mutation carriers which has undergone DL as part of an annual breast cancer screening program. All procedures were performed by the same 3 experienced clinicians. Furthermore, this represents the first formal assessment of emotional distress as a modifier of DL tolerability, and these data were collected using a widely-applied, clinically-validated psychometric tool, the BSI-18. All indices of tolerability were defined prior to enrollment of the first subject, and the analytic plan was stipulated in advance. Therefore, the study provides robust, high-quality information regarding the feasibility of adding DL to current breast cancer screening strategies for women at high genetic risk of breast cancer. Our data indicate that poor DL tolerability poses a significant barrier to its more widespread clinical application.To date, this is the largest group of women with known BRCA1/2 mutation-positive families or other healthy women in the general population who are at high risk of breast cancer. Therefore, our findings may not apply to a more general population of BRCA1/2 mutation carriers nor other women at high risk of breast cancer. However, we doubt that the presence of these highly-selected women in a study of DL tolerability specifically designed for woman from BRCA1/2 mutation-positive families biased the findings. Although a small proportion (15%) of participants had taken part in multiple prior NCI HBOC-related clinical research projects [The Breast Imaging Study is a single-institution intervention study of highly-selected women. Women who participated in this study are both highly-educated and highly-motivated to participate in clinical research. It is unlikely that this group of women is representative of all women from projects , the vasOur experience suggests that DL is not likely to play a central role in breast cancer screening among high-risk women, because women find it painful, are reluctant to undergo multiple DL examinations over time, and because the procedure has also failed to yield large enough numbers of exfoliated epithelial cells from high-risk women to permit reliable cytologic diagnosis or to support translational research activities ,13. In aIn conclusion, DL was introduced into clinical practice only nine years ago; consequently, systematic prospective studies of its tolerability are limited. Regardless of its ultimate utility as a diagnostic, risk assessment or research tool, for its use to be practical, it is essential that DL be well-tolerated. Despite vigorous attempts to obtain satisfactory local anesthesia (short of doing the procedure in the operating room), nearly 25% of our participants refused to repeat the DL one year later.The current study highlights the important relationships between measures of emotional distress, experience of DL discomfort and refusal of subsequent DL. Women who report high levels of emotional distress just prior to DL are three times more likely to refuse DL in the future. Additionally, women who were more distressed were more likely to report poor DL tolerability, and poor tolerability was associated with less acceptance of future DL. The identification of women who are emotionally distressed near the time of DL provides an opportunity to address the distress directly, either by using anxiolytic medications, rescheduling the appointment to a less stressful time, or referral for emotional counseling prior to DL.The identification of the quality of pain, e.g., sharp, burning, allows for refinement in the anesthesia of the breast nipple. Conscious sedation may be required for optimal pain relief in women who report emotional distress prior to DL or in women who experience significant levels of pain during DL. This, of course, would substantially increase both the cost and logistical difficulty of applying this tool in the clinic.Our experience  and otheThe authors declare that they have no competing interests.JTL drafted the manuscript, conceived of the study and participated in the study design, procedure performance and data collection. EBB performed the data analyses, drafted the results section of the manuscript and contributed to the development of the manuscript. KN coordinated all data and specimen collection. EBB's work on this manuscript was completed while in the Cancer Prevention Fellowship in the Divisions of Cancer Prevention and Cancer Control and Population Sciences at the National Cancer Institute. JP participated in the study design and in the manuscript preparation. RG participated in the specimen collection, study design and manuscript preparation. MHG provided senior leadership for the study, funding and participated in the manuscript development. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Serum concentrations of oestradiol-17β were measured daily throughout one menstrual cycle in 32 normal women, 31 women with benign disease of the breast and 10 with cancer of the breast. The concentrations were found to differ significantly from normal in women with cysts and to a lesser extent in those with cancer of the breast. In 25 normal post-menopausal and in 27 post-menopausal women with cancer repeated assays disclosed consistently low levels of oestradiol-17β.


Cancer screening programmes in England are publicly-funded. Professionals' beliefs in the public health benefits of screening can conflict with individuals' entitlements to exercise informed judgement over whether or not to participate. The recognition of the importance of individual autonomy in decision making requires greater understanding of the knowledge, attitudes and beliefs upon which people's screening choices are founded. Until recently, the technology available required that cancer screening be confined to women. This study aimed to discover whether male and female perceptions of cancer and of screening differed.Data on the public's cancer beliefs were collected by means of a postal survey (anonymous questionnaire). Two general practices based in Nottingham and in Mansfield, in east-central England, sent questionnaires to registered patients aged 30 to 70 years. 1,808 completed questionnaires were returned for analysis, 56.5 per cent from women.Women were less likely to underestimate overall cancer incidence, although each sex was more likely to cite a sex-specific cancer as being amongst the most common cancer site. In terms of risk factors, men were most uncertain about the role of stress and sexually-transmitted diseases, whereas women were more likely to rate excessive alcohol and family history as major risk factors. The majority of respondents believed the public health care system should provide cancer screening, but significantly more women than men reported having benefiting from the nationally-provided screening services. Those who were older, in better health or had longer periods of formal education were less worried about cancer than those who had illness experiences, lower incomes, or who were smokers. Actual or potential participation in bowel screening was higher amongst those who believed bowel cancer to be common and amongst men, despite women having more substantial worries about cancer than men.Our results suggest that men's and women's differential knowledge of cancer correlates with women's closer involvement with screening. Even so, men were neither less positive about screening nor less likely to express a willingness to participate in relevant screening in the future. It is important to understand gender-related differences in knowledge and perceptions of cancer, if health promotion resources are to be allocated efficiently. In England, enthusiasm for cancer screening has led to the establishment of organised national programmes, with direct costs being met by the publicly-funded National Health Service (NHS). Since the late-1980s, all women within prescribed age ranges have been invited routinely and regularly for testing for breast cancer and for cervical pre-cancers. The uptake in these two programmes is 75-80 per cent and it is claimed that, over the past 20 years, they have identified around 100,000 breast cancers and around 400,000 significant cervical abnormalities [Although health professionals advocate cancer screening on public health grounds, the prospective participant's decision to attend for screening is private. The outcome of that decision depends, in large part, on knowledge, attitudes and concerns with respect both to the disease and to the process of testing. Most of the research into the public's knowledge base conducted to date has been programme-specific and, as a consequence, sex-specific, presumably in view of men's or women's inability to participate directly in one or other of the particular screening services. Typically, only men are asked to provide opinions on screening for prostate cancer and only women are asked for their views on breast screening . MaintaiThis paper reports the findings of a study of men and women's beliefs about, and attitudes towards, cancer and screening. In particular, we were concerned to establish whether men and women differed in their knowledge of risk factors and whether one sex was more favourably disposed towards cancer screening than was the other. As it is traditionally supposed than men are less interested in preventive medicine than are women , signifiOur data were obtained via a questionnaire survey [additional file As with the previous local studies, we sought the assistance of general practitioners in distributing questionnaires. Two practices, one in Nottingham and one in Mansfield (approximately 12 miles to the north), agreed to send out questionnaires on our behalf. Although both practices were urban, the areas served by each differed in terms of socio-economic deprivation. On the Index of Multiple Deprivation .The general practitioners were provided with pre-prepared survey packages, each package containing an invitation letter, a blank questionnaire, a patient information sheet, and a pre-paid response envelope for the return of the completed questionnaire. The practices were asked to mail packages to registered patients aged between 30 and 70 years, but were granted discretion in exclusion. As with the previous studies, patients with a current diagnosis of cancer or with learning disabilities were excluded from the samples, on the grounds of the need to avoid distress and incapacity to complete the instrument, respectively. As the questionnaires were anonymous, we were unable to enhance compliance by contacting non-responders or to identify the non-responders' characteristics. All data were collected in late-2007 and, as far as the results reported here are concerned, all questions were closed-ended (mostly of the tick-box variety).The opening section of the questionnaire was entitled: "What do you know about cancer?". Subjects were asked, first, to estimate the number of newly-diagnosed cancer cases each year, by selecting one of six numerical values . As the true number lay between 275,000 and 350,000 , values Subjects were asked to rate each of eight cancer risk factors as a major risk, a minor risk, or as no risk. A "don't know" option was also available. We included increasing age, smoking tobacco and over-indulgence in alcohol use, all of which are generally presumed by health professionals to represent principal risk factors for most forms of cancer. We included being overweight and a lack of exercise, which are known to be risk factors for some of the more common cancers, such as breast and bowel. Sexually-transmitted infection is relevant for a few specific cancers only, although the association between human papillomavirus and cervical cancer is being publicised increasingly. We included two factors which are commonly-cited, although less-well-validated. These were, first, a family history of cancer (genetic risk), even though it "is uncommon for cancer to run in a family... Most of the time, multiple cases of cancer in a family are just a matter of chance" ( p.15). SEach subject was offered three true-or-false questions, namely, whether sun-bathing caused skin cancer, whether cancer was more common amongst women than it was amongst men, and whether more people died of heart disease than died of cancer. The first statement, of course, has long been accepted as true by both practitioners and public alike ,21 and wThree types of cancer screening currently available via the NHS - bowel, breast and prostate - were described briefly. We restricted discussion to these three types, on the grounds that men and women would each be eligible for two types only. We asked the respondents whether they believed that the NHS should continue to provide screening services such as these. They were also asked to indicate whether they had already been screened, or whether or not they would accept a test were one to be offered.The final section of the questionnaire was modelled closely on the instruments used in previous local studies ,9. It reWe planned two types of analysis. First, responses to the factual questions, such as estimated incidence, identity of most common cancers and risk factors, were examined with respect to male-female differences in proportions. Beyond establishing whether men's and women's judgements were accurate, we were concerned to establish whether opinions differed systematically by sex. Second, three specific beliefs or attitudes about cancer and screening were modelled using logistic regressions, again with a view of establishing the existence, or otherwise, of male-female differences. The dependent variables in the regressions were (i) the belief that the chances of getting cancer were above average, (ii) having substantial concerns about cancer, and (iii) actual or potential participation in bowel cancer screening. We restricted the analysis of participation to bowel screening, as this was the only type for which both sexes were eligible. All of the socio-demographic and knowledge variables were candidates for the models initially, which were re-estimated after excluding variables with insignificant coefficients.Out of 6,939 questionnaires distributed, 1,808 were completed and returned for analysis. The response rate (26.1 per cent) was similar to that achieved in a previous local study [Table Table Table 2 test, p = 0.21 or greater). A "don't know" response to both of the last two questions was offered by 10.1 per cent of the sample, with no significant difference between the sexes .With respect to the three true-or-false questions, nearly all subjects (98.7 per cent) agreed that sun-bathing was a skin cancer risk. The majority (53.3 per cent) did not accept that cancer was more common amongst women than it was amongst men, although 26.2 per cent reported "don't know". Two-fifths of the sample (41.5 per cent) thought (incorrectly) that more people died of heart disease than died of cancer, with 25.9 per cent reporting "don't know". For none of these questions did the proportions of male and female responses differ significantly  believed that cancer screening services should continue to be provided by the National Health Service. For breast cancer screening, 47.4 per cent of women reported that they had already been screened, and a further 48.4 per cent indicated that they would take the test, were one to be offered. The corresponding proportions for prostate cancer screening amongst men were 7.4 per cent and 83.6 per cent, respectively. The higher rate of actual participation in breast cancer screening is to be expected, in view of the longer duration and higher public profile of that programme. Combining the actual and potential participation percentages, the proportion of women positively receptive to breast cancer screening was higher than the proportion of men receptive to prostate cancer screening . Interest in bowel cancer screening was slightly lower, with 6.8 per cent of men and women reporting a previous screen, and a further 80.3 per cent indicating a wish to be tested. Most people in the sample (69.6 per cent) assessed their chances of getting cancer as the same as the average for their age and sex, although 15.3 and 15.1 per cent believed that their chances were higher and lower, respectively. Most subjects (75.5 per cent) recorded either no or minor worries about cancer, the remainder having more substantial concerns (quite or very worried).Tables Our results did not confirm fully the hypothesis that each sex feels itself to be more vulnerable than the opposite sex to cancer . In our Although there exist few other both-sex studies of beliefs about cancer in general, several single-sex studies or both-sex studies of one or more cancer types have been undertaken. Several of our risk factor findings parallel those of earlier studies. First, age was under-rated as a risk factor for cancer by both men and women equally, being assessed as a major risk only by around one-third of subjects. An earlier British population study  also repWhere the assignment of a risk factor's severity differed significantly by sex Table , women rThe earlier British study  includedabsolute risk of cancer was negatively associated with age and positively associated with current smoking, alcohol consumption, having one or more relatives with cancer, low income, with being obese (but not with being overweight), and with being female [relative risk was negatively associated with age and with general health, and positively associated with a family history of cancer and being male. In so far as the American findings can be pooled, they seem to mirror our finding that current health status, family cancer, smoking and age are robust predictors of risk perception, whilst the significance of gender remains equivocal.Our regression analysis suggested that comparative risk perception was positively associated with illness experiences, smoking and being overweight, negatively associated with age and the current level of general health, and unrelated to gender. This result merits comparison with those of two USA population studies. First, a regression analysis of routinely-collected national socio-demographic and health data indicated that a high perceived g female . In the g female , high peThe variables in our model predicting heightened worries about cancer  are also reported as significant in the analysis and attendant literature review of the second US study cited above . NeitherContrary to the supposition that men are less interested in preventive medicine than are women , almost Our study has limitations. We elected to distribute questionnaires via general practitioners rather than by direct mailing. Experience has shown that this method achieves a much higher response rate, albeit at the risk of introducing bias. In the absence of detailed information on each subject offered a questionnaire, response bias by characteristic cannot be ascertained. Despite guidance from the investigators, practitioners' exclusions of potential respondents remained discretionary and unrecorded, although it is probable that the sample excluded a disproportionate number of subjects with cognition difficulties or with particularly close contacts with cancer. This having been said, detailed analyses of respondents in local bowel  and cervper se, each did believe a same-sex-specific cancer to be amongst the most common types. With respect to sexually-transmitted infections and family history as risk factors, men were more likely to admit ignorance, and less likely to perceive each as a major risk. In reality, each of these factors is more significant for female-specific cancers . Overall, our results suggest that knowledge of cancer correlates with women's closer involvement with screening. This having been said, men were neither less positive about screening nor less likely to express a willingness to participate in relevant screening in future, suggesting that personal experience alone fails to explain attitudes. Although women expressed more worries about cancer, men expressed the greater interest in bowel cancer screening.The development of national cancer screening services in England has strongly favoured women's health promotion opportunities compared with those of men's, owing to both biology and technology. Not surprisingly, in view of the nature of service provision, far fewer men than women in our sample had experienced screening. Given women's greater involvement in the process, therefore, we had anticipated that knowledge of cancer and attitudes towards screening would vary with sex. Compared with women, men were more likely to underestimate cancer incidence. Whilst neither sex believed themselves to be more susceptible to cancer Given differential knowledge, it is inevitable that differences exist between the sexes in the process of reaching screening decisions. In the past, health education and health promotion programmes have remained "gender blind", yet presuming gender or sex to be irrelevant to how people perceive and comprehend is a potential obstacle to the development of effective health promotion policies . InternaThe authors declare that they have no competing interests.The authors contributed equally to the design of the study, data analysis and the drafting of the manuscript. THS organised the data collection and was responsible for data entry.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/9/431/prepubQuestionnaire: Men and women: beliefs about cancer and about screening. Content of the questionnaire used for data capture.Click here for file


We investigated the association between plasma 25(OH)D and the subsequent colorectal cancer incidence risk by a nested case–control study in The Japan Public Health Center-based Prospective Study, covering 375 newly diagnosed cases of colorectal cancer from 38 373 study subjects during a 11.5-year follow-up after blood collection. Two controls were matched per case on sex, age, study area, date of blood draw, and fasting time. In a conditional logistic regression model with matched pairs adjusted for smoking, alcohol consumption, body mass index, physical exercise, vitamin supplement use, and family history of colorectal cancer, plasma 25(OH)D was not significantly associated with colorectal cancer in men or in women. However, the lowest category of plasma 25(OH)D was associated with an elevated risk of rectal cancer in both men (odds ratio (OR), 4.6; 95% confidence interval (CI), 1.0–20) and women , compared with the combined category of the other quartiles. Our results suggest that a low level of plasma 25(OH)D may increase the risk of rectal cancer. D-1α-hydroxylate to 1,25-dihydroxyvitamin D, which regulates calcium metabolism through its interaction with its major target tissues, bone and intestine; 25-hydroxyvitamin D is also metabolised in colorectal mucosa for regulation of cellular growth.Ecologic studies have reported that sunlight or solar ultraviolet B exposure is inversely associated with the risk of colorectal cancer incidence and mortality in the United States  and in JSeveral prospective studies reported that 25-hydroxyvitamin D in the blood was inversely associated with colorectal cancer risk  is an ongoing cohort study investigating cancer, cardiovascular disease, and other lifestyle-related diseases. The first group (Cohort I) of the JPHC study started in 1990 and the second group (Cohort II) in 1993 .Plasma 25-hydroxyvitamin D concentrations were measured by the competitive protein-binding assay of χ2 statistic. P-values for the trend were two-sided, with 0.05 as the significance level. We estimated the ORs for colorectal cancer as a whole, and also colon and rectal cancers separately with assessment of difference between these two cancers using a test for heterogeneity (−1 (37.5 nmol l−1)) . Percentages of baseline characteristics were unadjusted crude values. We used the extensions of the Mantel–Haenszel procedure  with matogeneity . To examColorectal cancer cases in men smoked more, consumed more alcohol beverages, and had a higher body mass index than their controls, but also consumed less dietary fiber than controls . Female n-3 polyunsaturated fatty acid intake in women, which is contained in fish, a major source of dietary vitamin D in the Japanese population ; 20.6 ng ml−1 in women and 22.6 ng ml−1 in their controls (P=0.093). There was no difference between colon cancer cases and their controls.Plasma 25-hydroxyvitamin D was lower in rectal cancer cases than their controls . Median P for trend, 0.39). It appeared that only the lowest quartile had a somewhat higher risk than other quartiles for rectal cancer risk, although again the trend test was not significant. The ORs were 1.0 for the lowest, 0.17 for the second, 0.25 for the third, and 0.075 for the highest quartile for men ; colon cancer did not show a similar association. In women, a similar association was observed for rectal cancer risk, with ORs of 0.26, 0.46, and 0.33 for the second, third and highest quartiles respectively . Heterogeneity tests between colon and rectal cancer risk were borderline , using estimates from the statistical model for the trend test.Plasma 25-hydroxyvitamin D was not associated with the risk of colorectal cancer in men or women, although there was a suggestion of an inverse relationship in men , with ORn-3 polyunsaturated fatty acid or fish intake did not change the main results (data not shown).In addition to the main results, we calculated the rectal cancer risk of the lowest quartile compared with the combined category of other quartiles in men and women. These ORs were 4.6  in men and 2.7  in women. The fact that the low plasma levels were associated with rectal cancer risk did not substantially change when the first 2-year cases were excluded, although the OR in men was attenuated  in men; OR, 2.7  in women). Further adjustment for We repeatedly examined the association after stratifying data by the season of blood collection, that is, that with high plasma levels (July to November) or low plasma levels (December to June), and by study location (northern or southern Japan), but the results did not substantially change. These further analyses could not be applied to rectal cancer separately because the numbers were too small; similarly the risk of hypovitaminosis D could not be investigated because of the small numbers .Our results suggest that a low level of plasma 25-hydroxyvitamin D is associated with rectal cancer risk in both men and women but not colon cancer. A significant inverse association between 25-hydroxyvitamin D and colorectal cancer, especially of the distal colon and rectum has been reported . On the other hand, the small Washington County Study covered a higher and narrower range (less than 17.2–30.1 ng ml−1 or more)  expression. VDR also has some differences in genetic polymorphisms by ethnic group. The Women's Health Initiative study reported that calcium plus vitamin D supplementation did not decrease the subsequent risk of colorectal cancer over a follow-up of 7 years  is shorter than that of 25-hydroxyvitamin D (approximately 2 weeks) and normal levels are maintained even with vitamin D deficiency and low 25-hydroxyvitamin D levels, making it unsuitable for studies of colorectal cancer risk .−1 for men and 22.8 ng dl−1 for women) than those drawn at other times . To minimise bias, we matched date of blood collection between cases and controls (within 3 months), differing by less than 1 month among 63% of the case–control pairs, only by 1–2 months among 14% of them, and by 2–3 months among 17%. The proportion of case–control pairs where both were drawn at high-level seasons of plasma 25-hydroxyvitamin D (April to October) was 72% of all pairs, so difference in timing of blood draw would minimally impact on risk estimates.Although blood samples were collected before cancer diagnosis, measurement errors may exist because only one blood sample for each subject was used to measure plasma 25-hydroxyvitamin D concentrations, causing random misclassification to attenuate statistical associations. Long-term storage is recommended only at temperatures of less than −18°C  and our In conclusion, a low plasma 25-hydroxyvitamin D level may be associated with a subsequent risk of rectal but not colon cancer.


Breast cancer risk education enables women make informed decisions regarding their options for screening and risk reduction. We aimed to determine whether patient education regarding breast cancer risk using a bar graph, with or without a frequency format diagram, improved the accuracy of risk perception.We conducted a prospective, randomized trial among women at increased risk for breast cancer. The main outcome measurement was patients' estimation of their breast cancer risk before and after education with a bar graph (BG group) or bar graph plus a frequency format diagram (BG+FF group), which was assessed by previsit and postvisit questionnaires.P = .10). Among women who inaccurately perceived very high risk (≥ 50% risk), inaccurate risk perception decreased significantly in the BG+FF group (22% to 3%) compared with the BG group (28% to 19%) (P = .004).Of 150 women in the study, 74 were assigned to the BG group and 76 to the BG+FF group. Overall, 72% of women overestimated their risk of breast cancer. The improvement in accuracy of risk perception from the previsit to the postvisit questionnaire  was not significantly different between the 2 groups (Breast cancer risk communication using a bar graph plus a frequency format diagram can improve the short-term accuracy of risk perception among women perceiving inaccurately high risk. A patient's knowledge of risks and benefits is crucial to informed decision making . A womanIn a report on risk communication, Lipkus and Hollands  showed tWe conducted a prospective, randomized trial to compare communication of breast cancer risk using a bar graph (standard of care) versus the bar graph in addition to a frequency format diagram (using highlighted human figures) among women at increased risk of breast cancer. The aim of this study was to determine whether patient education regarding breast cancer risk using a bar graph alone or with the addition of a frequency format diagram improved the accuracy of risk perception and to assess women's preference for risk information provided as a bar graph versus in a frequency format.In 2005, women aged 40 years or older presenting to the Breast Diagnostic Clinic at Mayo Clinic, Rochester, Minnesota, and considered to be at "increased breast cancer risk" (defined below) were eligible for the study. They were approached by the study coordinator to determine their interest in participation in the study and were provided detailed information regarding the study; interested persons provided informed consent. Women with prior breast cancer or lobular carcinoma in situ, receiving chemoprevention therapy , or with a history of prophylactic mastectomy were excluded. The study was approved by the Mayo Clinic Institutional Review Board.Women were considered at "increased risk" 1) if the Gail model risk estimate was greater than 1.66% for development of invasive breast cancer over the next 5 years, 2) if a breast biopsy showed atypical hyperplasia, 3) if at least 1 first-degree relative had breast cancer, or 4) if more than 2 second-degree relatives had breast cancer or ovarian cancer ,9.All participants completed a previsit questionnaire immediately preceding the visit, providing information on educational status, Gail model risk factors, and current plans for screening or risk reduction. Participants' own perception of their breast cancer risk was assessed as a 5-year estimated risk of invasive breast cancer using numerical values .The standard of care in our practice has been to use a bar graph to communicate breast cancer risk estimates. Hence, all participants received a bar graph. Subjects were first stratified by age (40–59 years ["younger"] and ≥ 60 years ["older"]); within each age group, subjects then were randomly assigned to 1 of 2 groups: one to receive a bar graph alone (BG group) and the other to receive both a bar graph and a frequency format diagram (BG+FF group) , each participant completed a postvisit questionnaire before leaving the breast clinic. The questionnaire assessed the patient's breast cancer risk perception , preference for the bar graph or the frequency format diagram (for women in the BG+FF group), plans for future breast cancer screening options and risk-reduction strategies, and satisfaction with the information provided during the counseling visit. Our report focuses on risk perception and format preference only.2 test or 2-sample t test, respectively. "Accurate risk perception" was defined as the participant's perceived risk estimate category matching her actual Gail model risk estimate category. Intention-to-treat analysis was used such that if a participant did not complete the postvisit questionnaire, the postvisit risk score was assigned the same score as the previsit score. The accuracy of risk perception was compared between the 2 groups using the Pearson χ2 test or logistic regression analysis to adjust for other factors. The difference in risk perception scores between the previsit and postvisit questionnaires was analyzed using the Wilcoxon rank sum test. The signed rank test was used to detect whether the risk score improved within each group. All P values less than .05 were considered statistically significant.The demographic characteristics of the study participants were calculated as frequencies (percentages) or mean ± SD and were compared between the 2 groups using the Pearson χOf the 154 subjects who expressed an interest in the study, 150 provided informed consent and completed the previsit questionnaire; 74 patients  were randomly assigned to the BG group and 76 to the BG+FF group  ; age also did not affect the scores (P = .57).In the overall assessment of risk perception, accurate risk perception was noted for 14 women  in the BG group before the visit and improved to 45 women  after the visit, whereas in the BG+FF group, the accuracy of risk perception improved from 10 women  before the visit to 51 women  after the visit. The previsit to postvisit changes in accurate risk perception are detailed in Figure P = .17).The results of the previsit and postvisit questionnaires, depicting patients' self-reported estimates of their risk compared with the actual Gail risk model results, are shown in Table P = .004). The difference between previsit and postvisit perception of high risk was greater in the BG+FF group (88% decrease) than in the BG group (33% decrease) (P < .001).Although none of the women in the study had Gail model risk estimates of 50% or greater, 21 women (28%) in the BG group and 17 (22%) in the BG+FF group reported such high risk on the previsit questionnaire , 34% (n = 26) "preferred frequency format," 15% (n = 11) "preferred bar graph," 43% (n = 33) felt that "both were just as good," and 8% (n = 6) had "no preference/don't know."Understanding breast cancer risk is a vital component of informed and participatory decision making ,11. AccuCombining visual displays with numerical and written information can be effective in communicating risk information . In our P = .10). Among women in the 2% to 9% risk category, discussion using either the bar graph alone or the bar graph plus the frequency format diagram improved the accuracy of risk perception, but the difference between the groups was not statistically significant. In contrast, among women who inaccurately perceived very high risk (≥ 50%), the BG+FF group had significantly improved accuracy of risk perception compared with the BG group (P = .004). In a previous report, Gigerenzer [In our study, no significant difference was noted in the accuracy of risk perception between the BG group and the BG+FF group (gerenzer  stated tgerenzer  used difIn a study of the effect of graphic format on perception of risk magnitude, Schapira et al  reportedIn a study of risk communication among medical inpatients aged 75 years and older, Fuller et al  found thPrevious studies of breast cancer risk perception found that women tend to overestimate their risk ,3. In thThe question of preference for format was addressed in the BG+FF group. One-third of these participants preferred the frequency format diagram, and 43% believed that it was just as good as the bar graph. Gigerenzer and Edwards  reportedThe strength of this study lies in the prospective, randomized study design, which enabled assessment of different formats for risk communication between 2 comparable groups of high-risk women. Women presenting to the breast clinic were participants in the study, and these results can be generalized to similar groups of high-risk women. We acknowledge, however, that this study has some limitations. The participant population was mainly white and had at least a high school education, which suggests that results may not be generalizable to all populations. In addition, numeracy could have affected understanding but was not addressed in this study and may have provided further insight into the study findings. Furthermore, we could not assess or control for the providers' oral explanations of breast cancer risk that could potentially have contributed to allocation bias, but providers were advised to use only the format or formats of communicating risk assigned to them for this study. Additional research is needed to assess retention of information over time because this study only assessed risk perception immediately after the visit.In summary, this study showed that breast cancer risk communication using a bar graph along with a frequency format diagram can improve the accuracy of risk perception, especially among women perceiving inaccurately high risk. Many women may prefer the frequency format, suggesting that incorporating both of these formats into clinical practice to communicate breast cancer risk is reasonable. Future studies to include larger populations of women with varying risk and educational status, and longer-term follow-up of the participants to assess sustained understanding of risk, are indicated in our efforts to enhance risk communication.The authors declare that they have no competing interests.KG, AKG, BJC, SP, CIW, REJ, DW-R, MKB, and SSC were involved in study conception and design. Data acquisition was performed by KG, BJC, SP, CIW, LN, NPS, REJ, DW-R, and MKB. SSC and KG performed the statistical analyses. KG drafted the manuscript, and all authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


S-transferases (GSTs) may modify this relation. To determine if breast cancer risk is associated with GSTM1 and GSTT1 genetic polymorphisms, and to evaluate the effect modification between GST genotypes and alcohol consumption in the risk of breast cancer, we conducted a case–control study in the state of Connecticut in the period 1998 and 2001. Cases were histologically confirmed, incident breast cancer patients in New Haven County, CT. Controls were randomly selected from women histologically confirmed to be without breast cancer. The study results show that, while GSTM1 genotypes were not associated with breast cancer risk, GSTT1-null genotype was associated with a significant 90% increased risk for postmenopausal women . Analysis by GST genotypes and alcohol consumption shows that GSTM1A ever-drinking women had a 2.5-fold  increased risk of breast cancer compared to the GSTM1A never-drinkers, and the risk increases with duration and daily amount of alcohol consumption. Postmenopausal women with GSTT1-null genotype, who consumed a lifetime of >250 kg of spirit-equivalents, had an almost seven-fold increased risk , and drinking commencing at younger ages appears to carry a higher risk. An OR of 8.2 (95% CI 1.2–57.4) was observed for those with GSTM1A, and GSTT1-null genotypes who had consumed a lifetime of >250 kg of spirit-equivalents. In conclusion, alcohol consumption may increase breast cancer risk among those who carry susceptible GST genotypes.Alcohol consumption has been inconsistently associated with breast cancer risk. Recent studies suggest that genetic polymorphisms of glutathione  S-transferases (GSTs) are considered to be particularly important for detoxifying many carcinogenic compounds and reactive intermediates that may be breast carcinogens , and the lack of functional GSTM1 enzyme activity. Studies have shown that individuals who inherit the GSTM1 null genotype are not capable of conjugating and detoxifying specific substrate epoxide intermediates . The participation rate was 71% for controls.After approval by each subject's hospital and physician, potential participants were approached by letter and then by phone. Those who consented were interviewed by a trained interviewer, either at home or at a location convenient for the patient. A standardised, structured questionnaire was used to obtain information on alcohol drinking, tobacco smoking, menstrual and reproductive history, lactation history, past medical history, family cancer history, occupation, diet and demographic factors. Information on lifetime alcohol consumption included the type of alcoholic beverage used, age at which drinking commenced, amount of alcohol consumed per day, the frequency with which the subject consumed each type of alcoholic beverage, the duration during which each type of alcoholic beverage was consumed and total duration of drinking.As recently reported elsewhere . AmplifiUnconditional logistic regression was used to estimate the association between GSTM1 and GSTT1 genetic polymorphisms and breast cancer risk, to evaluate the putative modification by GST genotypes of the effect of alcohol drinking on the risk of breast cancer, and to control for potential confounders. The average adult lifetime daily consumption of alcohol in grams and the total lifetime consumption in kilograms of spirit- equivalents were calculated by taking into account the frequency, the amount and the duration of consumption of each type of alcoholic beverage. For these analyses, grams of beer and fruit wine were converted into grams of spirit-equivalents as follows: grams of beer were divided by 8, grams of wine by 2, according to the approximate ratio of alcohol contents in beverages. Each amount was then multiplied by the weekly reported frequency of consumption of each type of alcoholic beverage and further divided by 7 to estimate average daily consumption. Finally, the total lifetime kilograms of spirit-equivalent consumption was estimated.Variables included in the final model were age (as a continuous variable), body mass index , lifetime months of lactation , age at first full-term pregnancy , family breast cancer history and menopausal status. Additional adjustment for other variables such as age at menarche, age at menopause, number of live births and use of exogenous hormones did not result in material change for the observed association; therefore, these variables were not included in the final model. Maximum likelihood estimates of the parameters were obtained using SAS .Neither of the GSTM1 allelotypes were significantly associated with breast cancer risk for all women combined or among pre- or postmenopausal women (data not shown). Among women with GSTT1-null genotype, however, there was a significant, 50%, increase in breast cancer risk for all women combined . Further analysis by menopausal status indicates that this risk was limited to postmenopausal women .Table 1The relation between alcohol consumption and breast cancer risk by GSTT1 genotype is presented in Table 2videnced  by a 60%The data suggest that the more alcohol that postmenopausal women with GSTT1-null genotype consume, the greater their risk of breast cancer (Table 3Table 4The results of this study suggest that there is an increased risk of breast cancer associated with alcohol consumption among those carrying certain genotypes. We found that postmenopausal women with a GSTM1A genotype have an increased risk of breast cancer when they drink, and the risk increases with increasing amount and duration of alcohol consumption. We also found that breast cancer risk is increased for postmenopausal women with the GSTT1-null genotype who consume more than 250 kg of spirit-equivalents. An eight-fold significantly increased risk was observed among heavier drinkers who had GSTM1A and GSTT1-null genotypes.Alcohol consumption has previously been associated with breast cancer risk, but the results have been inconsistent . Other pGSTs are involved in the metabolism of a wide variety of potential carcinogenic compounds, including peroxides, organic epoxides, aromatic amino/nitro compounds and steroids. GST isozymes, such as GSTM1 and GSTT1, have distinct but overlapping substrate specificity as reviewed by The role of GSTT1 in the risk of breast cancer is supported by earlier studies (A potential limitation of this study and other earlier studies (In conclusion, this is the first study using detailed information on lifetime alcohol consumption to examine the effect of alcohol consumption on the risk of breast cancer by GST genotypes. The results of this study suggest that alcohol consumption may increase breast cancer risk among those who carry susceptible GST genotypes. A potential effect modification between GST genotypes and alcohol consumption in the development of breast cancer is biologically plausible. If this association is causal, the high frequency of the at-risk GST genotypes in the population means that avoidance of exposure among individuals with these susceptibility genotypes should result in a substantial reduction of breast cancer cases. If future studies demonstrate that alcohol consumption is, indeed, a risk factor for breast cancer among individuals with high-risk GST genotypes, alcohol consumption would be one of the few modifiable risk factors for breast cancer identified to date.


Heterozygous carriers of ATM-mutations have an increased risk for the development of breast cancer. The purpose of this study is to evaluate the association between ATM exon39 5557G > A  polymorphism and breast cancer susceptibility with the use of a meta-analysis.Emerging evidence suggests that ATM D1853N polymorphism and breast cancer risk were calculated using fixed- or random-effects model based on the degree of heterogeneity among studies.By searching PubMed and Embase databases, a total of 9 epidemiological studies with 4,191 cases and 3,780 controls were identified. Crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) for ATM D1853N polymorphism and breast cancer risk was observed in overall analysis .No significant association between the ATM D1853N polymorphism is not a risk factor for developing breast cancer.Our results indicate that  A-T ied (ATM) . ATM, a ed (ATM) .ATM gene, located on chromosome 11q22-23 and consisting of 66 exons, has been reported to be involved in numerous damage repair signaling pathways and cell-cycle checkpoints [ATM gene has been detected in approximately 40% of human sporadic breast tumors [ATM missense variant resulted in a shorter mean interval to develop a second tumor than patients without radiation treatment and ATM germline mutation [The ckpoints ,6. Loss t tumors -11. Breamutation . Previoumutation -18. In cATM exon39 5557G > A  may be considered as a predisposition factor for developing breast cancer, especially in cancer-prone pedigrees [ATM D1853N polymorphism and breast cancer risk, but the evidence regarding the role of ATM as a genetic marker for breast cancer is conflicting. In order to provide stronger evidence for estimating the association, a meta-analysis was performed.Recently, Mehdipour et al. reported that a common single nucleotide polymorphism edigrees . To dateATM" and "breast cancer" and "polymorphism" or "variant" in PubMed and Embase databases . Additionally, we checked all relevant publications to retrieve the most eligible literatures.We searched the articles using the following terms "ATM D1853N polymorphism and breast cancer risk; (b) case-control studies; (c) sufficient published data for calculating odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs). The following information was collected independently by two investigators (Gao LB and Pan XM) from each study: first author's surname, year of publication, country, ethnicity, number of cases and controls with various genotypes, genotyping techniques, quality control for the genotyping methods, Hardy-Weinberg equilibrium (HWE) and minor allele frequency (MAF) in controls (Table The inclusion criteria were used for the literature selection: (a) articles about ATM D1853N polymorphism and breast cancer risk. The pooled ORs were calculated for heterozygote comparison (GA versus GG), homozygote comparison (AA versus GG), dominant model (GA/AA versus GG) and recessive model (AA versus GA/GG), respectively. The statistical heterogeneity among studies was checked by Q-test and 2 Istatistics [P value greater than 0.10 for Q-test, indicating absence of heterogeneity, the fixed-effects model (the Mantel-Haenszel method) was used to calculate the pooled OR [The process of meta-analysis in the current study was performed as described previously in detail -22. In batistics . If the ooled OR ; otherwiooled OR . Publicaooled OR . All staATM D1853N polymorphism and breast cancer susceptibility were available for this meta-analysis. The main characteristics of eligible studies are summarized in Table Overall, nine studies involving 4,191 cases and 3,780 controls about ATM D1853N polymorphism and breast cancer risk was observed. After subgroup analyses according to ethnicity, significantly increased risk was observed in South American population  but not in European and mixed populations.The main results of this meta-analysis are shown in Table P > 0.05).Begg's funnel plot was used to identify the potential publication bias of literatures on breast cancer, and the results did not show any evidence of publication bias in any comparison model  was not significantly associated with breast cancer susceptibility [ATM D1853N polymorphism is not a risk factor for developing breast cancer, although a significantly increased risk of breast cancer in ATM-heterozygous carriers has been reported [Previous studies have inconclusive results about the association between tibility . This fireported -18.ATM D1853N polymorphism was associated with a significantly increased risk of breast cancer in South American population (heterozygote comparison and dominant model) but not in European and mixed populations. The reason for these discrepancies is not very clear. There are, however, some possible reasons. Firstly, the ATM D1853N polymorphism may present with different frequencies in different populations and as a result may be associated with different degrees of breast cancer risk among different ethnic populations. Secondly, the genotype distribution in the controls of a South American study was departed from Hardy-Weinberg equilibrium [After subgroup analyses according to ethnicity, we found that the ilibrium , indicatilibrium ,29. TherSome limitations of this meta-analysis should be taken into consideration. On the one hand, the numbers of cases and controls analyzed for D1853N (rs1801516) found in the literature is still very small and might not precisely answer the given question. Especially, for some subgroup analyses, the statistical power is so low that caution should be taken in interpreting these results, even though positive association was found in South American population. On the other hand, data were not stratified by age at menarche, number of full-term pregnancies, menopausal status, and other suspected factors due to absence of available information.ATM D1853N polymorphism is not associated with breast cancer risk, indicating that this polymorphism is not an independent risk factor for the development of breast cancer. Well-designed, unbiased studies with a wider spectrum of subjects should be of great value to explore other potential risk factors.In conclusion, the overall outcomes of this meta-analysis have shown that the The authors declare that they have no competing interests.GLB, PXM, and Zhang L designed the study, and wrote the manuscript; SH, WX, and RL performed data acquisition; LLJ performed quality control of data; LWB, LML, and YWZ performed statistical analysis and interpretation. All authors read and approved the final manuscript.


P= 0.001). Genetic counselling produced a modest shift in the accuracy of perceived lifetime risk, expressed as an odds ratio, which was maintained at 12 months' follow-up. A significant minority failed to benefit from genetic counselling; 77 women continued to over-estimate their risk and maintain high levels of cancer-related worry. Most clinic attenders were inaccurate in their estimates of the population risk of breast cancer with only 24% able to give the correct figure prior to genetic counselling and 36% over-estimating this risk. There was some improvement following genetic counselling with 62% able to give the correct figure, but this information was poorly retained and this figure had dropped to 34% by the 1-year follow-up. The study showed that women attending for genetic counselling are worried about breast cancer, with 34% indicating that they had initiated the referral to the genetic clinic themselves. This anxiety is not alleviated by genetic counselling, although women reported that it was less of a problem at follow-up. Women who continue to over-estimate their risk and worry about breast cancer are likely to go on seeking unnecessary screening if they are not reassured. © 1999 Cancer Research CampaignThe present study investigated: (1) perception of genetic risk and, (2) the psychological effects of genetic counselling in women with a family history of breast cancer. Using a prospective design, with assessment pre- and post-genetic counselling at clinics and by postal follow-up at 1, 6 and 12 months, attenders at four South London genetic clinics were assessed. Participants included 282 women with a family history of breast cancer. Outcome was measured in terms of mental health, cancer-specific distress and risk perception. High levels of cancer-specific distress were found pre-genetic counselling, with 28% of participants reporting that they worried about breast cancer ‘frequently or constantly’ and 18% that worry about breast cancer was ‘a severe or definite problem’. Following genetic counselling, levels of cancer-specific distress were unchanged. General mental health remained unchanged over time . Prior to their genetics consultation, participants showed poor knowledge of their lifetime risk of breast cancer since there was no association between their perceived lifetime risk (when they were asked to express this as a 1 in x odds ratio) and their actual risk, when the latter was calculated by the geneticist at the clinic using the CASH model. In contrast, women were more accurate about their risk of breast cancer pre-genetic counselling when this was assessed in broad categorical terms (i.e. very much lower/very much higher than the average woman) with a significant association between this rating and the subsequently calculated CASH risk figure (


In vitro and in vivo studies have shown that cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of oestrogens. There is evidence that grapefruit, an inhibitor of CYP3A4, increases plasma oestrogen concentrations. Since it is well established that oestrogen is associated with breast cancer risk, it is plausible that regular intake of grapefruit would increase a woman's risk of breast cancer. We investigated the association of grapefruit intake with breast cancer risk in the Hawaii–Los Angeles Multiethnic Cohort Study, a prospective cohort that includes over 50 000 postmenopausal women from five racial/ethnic groups. A total of 1657 incident breast cancer cases were available for analysis. Grapefruit intake was significantly associated with an increased risk of breast cancer  for subjects in the highest category of intake, that is, one-quarter grapefruit or more per day, compared to non-consumers (Ptrend=0.015). An increased risk of similar magnitude was seen in users of oestrogen therapy, users of oestrogen+progestin therapy, and among never users of hormone therapy. Grapefruit intake may increase the risk of breast cancer among postmenopausal women. P450 3A4 (CYP3A4) system was discovered accidentally in 1989 during a study designed to test the effect of ethanol on a calcium-channel blocker  and information on demographic factors, personal behaviours, prior medical conditions, use of medications, family history of common cancers, and, for women, reproductive history and use of oral contraceptives and hormone therapy (HT). The study was approved by the Institutional Review Boards of the University of Hawaii and the University of Southern California. Further details regarding the study have been given elsewhere  from the baseline FFQ fell outside a defined valid range . Incident cancers in Hawaii were identified using the statewide Hawaii SEER registry and the CCR was used to identify cases who had moved to California. A software program was used to conduct a probabilistic data linkage using social security number, name, and date of birth. We had a social security number on 98.7% of the cohort. Further, we determined that after an average period of 7 years in the cohort, the out-migration rate was 3.7% . Although the out-migration rate is somewhat higher for Hawaii, California is the primary destination for these migrants, so that most remain under surveillance for cancer incidence. Mortality was determined by annual linkage to state death files in California and Hawaii, and periodically to the National Death Index. Follow-up time began on the date the respondent completed the baseline questionnaire and, for the analysis reported here, continued through 31 December 2002. Subjects were censored at the date of last follow-up, date of death, or date of diagnosis of cancer, whichever occurred earlier.The methods for dietary assessment have been described in detail elsewhere  and progestin therapy (PT) separately in the baseline questionnaire. Oestrogen+progestin therapy (EPT) was calculated based on the overlap between reported periods of ET and PT use , were estimated using log-linear regression proportional hazard models stratified on age at recruitment (single year), year of recruitment (single year), race/ethnicity , and study centre . We examined grapefruit intake by categories of both absolute intake  and intake per 1000 kcal . The highest category of absolute intake (⩾60 g) was an average of slightly greater than ¼ grapefruit per day or ½ every other day. The highest category of intake density was roughly equivalent. Categories were determined by usual serving size (as defined above) from the FFQ and the intake distribution for all subjects. Non-dietary factors considered as potential confounders included age at menarche , age at first live birth , parity , age at and type of menopause , postmenopausal oestrogen and/or progestin use (as defined above), weight (continuous) and height (continuous) at recruitment, physical activity (continuous variable for hours per day engaged in vigorous work and/or strenuous exercise), family (mother or sister) history of breast cancer (yes/no), education level attained , and smoking status at baseline . Dietary factors considered as potential confounders included intakes of alcohol, total energy, saturated fat, total dietary fibre, and soluble and insoluble fibre fractions. The dietary fibre value used in the present study is that published in the USDA tables and is the sum of lignin and non-starch polysaccharides in plant foods  and STATA  statistical software packages. Testing for significance was performed using likelihood ratio methods. All A total of 1657 of the women in the defined cohort were diagnosed with incident breast cancer before 31 December 2002 and are included in the analysis. Some baseline characteristics of the breast cancer cases and the total study population are shown in 1) estimate was adjusted for (stratified on) age at recruitment, year of recruitment, race/ethnicity, and study centre. Intake of ¼ grapefruit or more per day is associated with a 21% increase in breast cancer risk =1.00–1.46, Ptrend=0.044); the highest category of grapefruit density  is also associated with increased breast cancer risk . Second relative risk (RR2) estimate was adjusted (stratified) as above, and further adjusted for weight, height, physical activity, education, age at menarche, age at first birth, parity, age at and type of menopause, menopausal oestrogen/progestin use, cigarette smoking, family history of breast cancer, alcohol, saturated fat, total dietary fibre, and soluble fibre. With these adjustments, intake of ¼ grapefruit or more per day is significantly associated with a 30% increase in breast cancer risk ; the highest category of grapefruit density is likewise associated with a 25% increase in breast cancer risk . The increase in RR from RR1 to RR2 was due to adjustment for total dietary fibre and soluble fibre; adjustment for insoluble and soluble fibre produced almost identical results (data not shown).Ptrend=0.038). There is no trend among past HT users. For current ET users, there is an increase in risk of 36% from the lowest (zero) category of intake to the highest (Ptrend=0.22); for current EPT users, breast cancer risk increases 27% from the lowest to the highest category of grapefruit intake (Ptrend<0.13). There was a dose–response relationship between grapefruit intake and breast cancer risk in never HT users and in current ET and EPT users. Although the trend tests are not significant for current ET and EPT users, the pattern is the same in the three groups, and there is no statistical evidence that the magnitudes of the trends differ.The associations between grapefruit intake and breast cancer risk by category of HT use are shown in 2). Subjects were divided into two categories: lean/normal weight (BMI<25.0) and overweight/obese (BMI⩾25.0). The association between grapefruit intake and breast cancer risk was not modified by BMI, as shown in Ptrend=0.011). Among overweight/obese subjects, breast cancer risk increases 26% from the lowest to the highest category , although the test for trend is not statistically significant.We examined whether the association of grapefruit intake and breast cancer risk was modified by body mass index (BMI: weight in kilograms/(height in metres)To our knowledge, this is the first report of a commonly consumed food that may increase the risk of breast cancer among postmenopausal women. Whole grapefruit intake was significantly associated with breast cancer in the present study – generally, a 30% increase among subjects who consume the equivalent of ¼ grapefruit or more per day.To reduce measurement error in dietary assessments, investigators often energy-adjust intakes by calculating densities, that is, g per 1000 kcal of total energy intake. Densities represent the contribution of a particular nutrient or food group in relation to overall dietary intake as measured by the FFQ . HoweverThe measure of grapefruit intake in the present study, based on intake of the whole fruit, is an underestimation of total intake owing to a lack of information on grapefruit juice. If one makes the assumption that grapefruit juice intake is highly correlated with whole fruit intake, then the magnitude of risk observed in the present study is biased upwards; it represents the risk of breast cancer owing to total intake not just whole fruit intake. However, if there is little correlation between whole grapefruit and grapefruit juice intakes, and if one accepts that grapefruit juice intake increases breast cancer risk in the same manner as the whole fruit, then the magnitude of risk observed in the present study may be an underestimation of the true risk. This requires further study.−1 from the lowest to the highest quintile of dietary fibre intake , whereas soluble fibre, after adjustment for dietary fibre, was associated with an increase in oestradiol from 6.8 to 11.5 pg ml−1 from the lowest to the highest quintile of intake  (Beginning in the 1980s, it was hypothesised that dietary fibre may have a beneficial effect on breast cancer incidence by lowering endogenous oestrogen levels through the partial interruption by dietary fibre of the enterohepatic recirculation of oestrogens . While r1 to RR2 in in vitro evidence that certain fibre components, particularly lignin, have the ability to adsorb oestrogen, the adjustment will provide a more accurate estimate of breast cancer risk associated with grapefruit intake.In the present study, the addition of total dietary fibre and soluble fibre to the statistical model modified the estimate of breast cancer risk associated with grapefruit intake (RRConsistent with other studies on postmenopausal oestrogen use, we found an increase in breast cancer risk, particularly among current EPT users. One aim of our study was to examine the risk of breast cancer associated with grapefruit intake by subgroup of menopausal HT use. As endogenous oestrogens are metabolised in the same manner as exogenous estrogens , we had The association between grapefruit intake and breast cancer risk was clearly seen in never HT users, as well as current ET and EPT users. Interestingly, the RR of breast cancer associated with consumption of ¼ grapefruit or more per day compared to non-consumers was 44% higher among women who had never used HT, 36% higher in current ET users, and 27% higher among current EPT users. The risk of breast cancer associated with consumption of grapefruit was 32% higher among lean/normal weight women and 26% higher among overweight/obese women. Taken together, these results for HT and BMI suggest that the risk of breast cancer associated with grapefruit intake is stronger for subgroups of women with lower circulating oestrogen levels.−2 (This finding of a reduced effect of grapefruit in women with a higher BMI is similar to the lower effect of ET on breast cancer risk in women with a higher BMI (Previous studies have reported that the magnitude of interaction between a drug and grapefruit juice is markedly variable among individuals . SubjectIn our study of grapefruit intake and serum oestrogen levels, we observed an approximately 30% increase in oestrone and a 10% increase in oestradiol levels among women who consumed the equivalent of ¼ grapefruit or more per day. In the present study, we observed a 25–30% increase in breast cancer risk in the highest category of grapefruit intake. The meta-analysis of the relationship between levels of endogenous sex hormones and breast cancer risk in postmenopausal women by the Endogenous Hormones and Breast Cancer Collaborative Group (It is biologically plausible that grapefruit intake may increase the risk of breast cancer among postmenopausal women. However, the results of the present study need to be confirmed in other studies with more comprehensive measures of grapefruit intake that include both the whole fruit and grapefruit juice.