Both obesity and type 2 diabetes are among the risk factors for breast cancer development. Combined effect of these metabolic abnormalities on breast cancer risk however, has not been examined in premenopausal women. We tested this association in type 2 diabetic women, categorized as obese, overweight and normal body weight groups based on BMI.A total of 101 subjects were included in this study. Serum levels of IL-6, TNF-α, C reactive protein, leptin, TGF-α, adiponectin and insulin were measured by ELISA. Data were logarithmically transformed for variables not normally distributed. Analysis of variance with post-hoc Bonferroni was applied to compare the data between the groups. Simple and partial correlation coefficients between the variables were determined and a stepwise multiple linear regression analysis was performed to determine the relationships between the variables of interest.Significantly increased levels of IL-6, C reactive protein, leptin and significantly decreased levels of adiponectin were found in obese group, while the levels of TNF-α and TGF-α were unaltered. A positive correlation between waist circumference and IL-6 was found in obese group. Similarly, C reactive protein, waist and hip circumferences were linearly correlated with BMI in obese group. Stepwise multiple linear regression analysis revealed several significant predictors for breast cancer risk.Obesity and type 2 diabetes, owing to their effects on adipocytokines and inflammatory mediators, contribute to increased breast cancer risk in premenopausal women. This study emphasizes healthy life style and better management of these metabolic disorders to avoid the pathogenesis of breast cancer and of other chronic diseases. Obesity and type 2 diabetes mellitus (T2DM) remained major public health issues in the developed nations and their incidence is on the rise in the developing countries, attributed mainly to a considerable shift in the dietary practices ,2. On thObesity and T2DM also have in common an altered production of adipocytokines including leptin and adiponectin ,10. It hWhile majority of studies have indicated an inverse or absence of association of T2DM or obesity with premenopausal breast cancer risk, to our knowledge, none of the studies has examined the combined effects of these metabolic abnormalities in premenopausal women clinically asymptomatic for breast cancer. We tested this association in type 2 diabetic premenopausal women after categorizing them as normal body weight, overweight and obese groups based on BMIs.The subjects with T2DM were recruited from the roster of diabetic patients attending the outpatient unit of the Diabetes Center, King Abdulaziz University Hospital, Riyadh, Saudi Arabia. A total of 235 subjects were contacted for their willingness to participate in the study. Of these, 108 subjects provided their consents. From this cohort, 7 subjects were excluded from the study for the existence of clinical complications other than T2DM to avoid the misinterpretation of the data. Thus, this cross sectional study included 101 Saudi women clinically diagnosed with T2DM. Subjects were categorized based on BMI as normal weight, overweight and obese groups. Written and informed consents as well as completed generalized questionnaire were obtained from all the participants prior to their inclusion in the study. This study was conducted in accordance with the guidelines set by the ethics committee of the King Saud University, Riyadh, Saudi Arabia.2). Waist (cm) and hip (cm) circumferences were measured and waist-to-hip ratio was determined. Blood pressure (mm. Hg) was measured twice after 30 minutes of rest using the conventional mercurial sphygmomanometer and the values of the readings were averaged.Anthropometric measurements with emphasis to clinical markers of adiposity were obtained. BMI was calculated by dividing the weight (kg) with height  were determined using routine laboratory methods. Insulin was analyzed by a solid phase enzyme amplified sensitivity immunoassay . Serum levels of leptin, TNF-α, CRP, IL-6 and adiponectin were measured by ELISA . TGF-α was measured using immunological techniques . Homeostasis model assessment (HOMA) was applied to evaluate fasting insulin resistance using the formula; glucose (mmol/L) × insulin (u μl/mL)/22.5.SPSS version 11.5 for windows  was employed for statistical analysis of the data. Frequencies were presented in percent (%) of cases. Data was logarithmically transformed for variables, including insulin, TGF-α, triglycerides, leptin, CRP, IL-6 and HOMA-IR, for not being normally distributed. Analysis of variance with post-hoc Bonferroni was applied to compare the data between the groups. Simple and partial correlation coefficients between the variables were determined and a stepwise multiple linear regression analysis was performed to determine relationships between the variables of interest using IL-6 as the dependent variable and all other parameters as independent variables. Significance was set at P-value < 0.05.P< 0.04) between IL-6 and waist circumference in obese group  group as well as in overweight group   as compared to women with normal BMI Table . Among tp Figure , while t) Figure  and 1B. In a stepwise multiple linear regression analysis, using IL-6 as the dependent variable and all other parameters as independent variables, leptin was found to be a significant predictor among the overweight group  and TGF-α, CRP and BMI for the normal weight group  Table . IL-6 waObesity is increasingly associated with postmenopausal breast cancer risk, whereas, in premenopausal women there is an inverse relationship between BMI and the risk ,32. HoweDiabetic condition induces changes in several hormonal systems, including insulin, insulin like growth factors, estrogens and other cytokines that may affect the breast cancer risk. Characteristics of T2DM including insulin resistance and the resultant hyperinsulinemia are strongly correlated with postmenopausal as well as pre-menopausal breast cancer risk ,7. HyperObesity and T2DM also have in common an increased production of leptin and a decreased production of adiponectin ,10. SuchInflammation is associated with poor prognosis and decreased survival in many cancers. Obesity per se is considered a subclinical inflammation and thus, as markers of inflammation and their positive role in breast carcinogenesis, the increased levels of IL-6 and CRP in obese women in the present study are consistent with the breast cancer risk. Importantly, in obese women, a positive correlation between IL-6 and waist circumference, which itself is an independent risk factor for breast cancer, suggests obesity induced inflammatory response and enhanced risk for carcinogenesis. In addition, CRP is positively correlated with leptin and inversely with the adiponectin levels ,19. ThusWe acknowledge several limitations in this study. Due to small sample size especially in normal and overweight groups, some of the associations might be altered if analyzed on a larger sample size. Though, the presence of diabetic status in the studied subjects itself was found to be a risk factor for breast cancer in our study, we did not verify this finding by comparing with non diabetic normal control subjects. Additionally, conclusions made in this study were based on the prevalence of breast cancer risk factors in obese and T2DM subjects, while not directly evaluating these risk factors in the breast cancer patients. Due to cross sectional nature of this study and small sample size the observations need to be followed up with much larger sample size and in a prospective setup to make a causal inference.In summary, we found the presence of increased breast cancer risk in obese type 2 diabetic premenopausal women. Furthermore, altered expression of inflammatory mediators and the adipocytokines in obese diabetic women may collectively promote the breast cancer etiology as compared to women with normal body weight. Since the association of adipocytokines and inflammatory markers with breast cancer has been firmly established, our objective to measure these parameters in obese T2DM subjects while not in breast cancer cases was to assess whether the existence of these metabolic abnormalities confers an additional risk to develop the breast cancer. In this context, findings of this study attain significance in predicting the breast cancer risk and avoiding its carcinogenesis. Additionally, this study recommend a healthy life style, regular physical activities and a healthy diet to counter the growing epidemics of obesity, T2DM and associated disorders such as breast cancer and cardiovascular diseases.The authors declare that they have no competing interests.NMA; designed and conceived the study, participated in preparing the draft. MSA; carried out the biochemical measurements and obtained the data, participated in statistical analysis. OSA; Helped design and conceive the study, critically evaluated the draft. TH; Analyzed and interpreted the data, drafted the manuscript, participated in biochemical measurements. All authors read and approved the final manuscript.


In a cohort of 10 998 men and women, 95 incident cases of colorectal cancer were recorded after 17 years. Risk increased in association with smoking, alcohol, and white bread consumption, and decreased with frequent consumption of fruit. The relative risk in vegetarians compared with nonvegetarians was 0.85 (95% CI: 0.55–1.32). A genetWe aimed to examine the relationship of lifestyle and dietary factors with the incidence of colorectal cancer in a cohort that included a large proportion of vegetarians. In particular, we sought to examine whether the risk for colorectal cancer is lower in vegetarians than in meat-eaters, and low in participants who reported consuming relatively large amounts of fruit or vegetables and other foods high in fibre.The Oxford Vegetarian Study , date of birth, occupation, height and weight, and medical history  were also included. The validity of the questionnaire has been examined for estimating dietary fibre intake, but not for other nutrients , and could be classified according to their smoking status and alcohol consumption. Participants were followed up to 31 December 1999, subject to censoring at age 90.−1 and >7 u week−1). The statistical analysis was performed using the STATA statistical package  and sex. Further adjustments were made for smoking status  and alcohol consumption , although the association was no longer statistically significant after adjusting for smoking and alcohol. Participants eating 15 or more slices of white bread per week compared with those eating less than 15 had significantly higher risk , which remained highly significant after adjusting for alcohol and smoking.After adjusting for alcohol intake, both current and former smokers had an increased risk of colorectal cancer compared with the never smokers . Among the other lifestyle factors, social class, exercise, alcohol consumption, and body mass index were not significantly associated with the risk of colorectal cancer.This prospective study had a wide variation in diet due to the inclusion of a large proportion of vegetarians. The main limitation is the relatively small number of colorectal cancer cases and the lack of sophistication of the food frequency questionnaire.The present analysis did not find a significant difference in risk between nonvegetarians and vegetarians. Furthermore, no increase in risk of colorectal cancer was seen with higher meat consumption among nonvegetarians. Nevertheless, the lack of statistical association may reflect the relative small number of cases. A previous analysis of mortality in this cohort , cancer Fresh or dried fruit consumption was found to be significantly associated with colorectal cancer risk, although this association became nonsignificant after adjusting for alcohol and smoking. An approximately 40% decrease in risk was seen in people eating fresh or dried fruit five or more times per week compared with persons eating less than this amount. We did not observe a significant association for brown bread and risk of colorectal cancer, but a two-fold increase in risk was detected in those consuming 15 or more slices of white bread per week. White bread consumption may be a marker of an unhealthy diet, although an adverse association of refined carbohydrates with risk has been noted before (Our study suggested that smoking was associated with an almost two-fold increase in risk of colorectal cancer, although this association was attenuated by adjusting for alcohol consumption. The apparent adverse effect of alcohol was also partially confounded by smoking. Both the WCRF report  and a co


Sir,In their letter with regard to our paper on induced abortions and breast cancer, Brind and Chinchilli essentially suggest that residual confounding by age at first birth and parity may have caused us to underestimate the odds ratio (OR) for breast cancer in relation to induced abortion. We disagree. In paragraph 2 of their letter, they suggest that women in China who did not have an induced abortion would be more likely to be nulliparous and to have had their children later in life than women who had an abortion, that the women unexposed to abortions were therefore at higher risk of breast cancer than those with an abortion, and that the true OR in relation to induced abortion was thus underestimated. This is not correct. Few women in our study cohort were nulliparous and, as stated in our paper, the results were virtually unchanged when the analyses were restricted to gravid or parous women. Because of the one child per family policy in China, which became operational in the early 1980s, older women in our study tended to have larger numbers of children than younger women, and to have begun child bearing at an earlier age. Because of this, after controlling for age, the number of children was not a confounder, and age at first birth was only a weak confounder. During the time period covered by our study, abortions were almost always performed to limit family size. The decision to have an abortion would thus have been made after the birth of ones first child. Therefore, age at first birth would not necessarily be earlier for women with an abortion than for women of the same age without an abortion, as Brind and Chinchilli contend.Brind and Chinchilli point out that our crude OR for breast cancer in relation to induced abortion is 0.93, and our OR adjusted for age and age at first birth is 1.06. In the next paragraph, they suggest that confounding by parity and age at first birth would somehow not be fully controlled for by adjustment because of the high prevalence of induced abortion (51%) in our study population, and therefore that the OR of 1.06 should actually be higher. We fail to understand how the prevalence of the exposure could directly influence the confounding effect of other factors. If one were to  conduct a randomised trial of abortion and breast cancer, the most efficient design would be to assign 50% of the women to an abortion group and 50% to a control group. Confounding would be controlled for by the randomisation. In our study, confounding was essentially controlled for by stratification on the potentially confounding variables of concern. With a prevalence of exposure to abortions of 51%, we have the optimal power to detect a true association and to control for confounding. If the prevalence of abortions in the population were closer to 0%, it would have been more difficult to control for confounding by stratification because of smaller numbers in the exposed group.The contention in the sixth paragraph of the letter that the lower relative risk in the study by Sanderson than in our study is due to more residual confounding as a result of a higher prevalence of abortions in the Sanderson study is unwarranted. There are many reasons for differences in results between studies. In fact, the results of the Sanderson study and ours are very close , and provide consistent evidence that induced abortions probably do not cause breast cancer.In the case–control study nested within our cohort, controls were matched to cases on exact year of birth, and the potentially confounding effects of parity and age at first birth were controlled for in the statistical analysis. Brind and Chinchilli suggest that we should have also matched on these two factors. We disagree with their contention that this would have given a more accurate estimate of the OR. Our sample size was large enough to allow us to control tightly for these two variables. Tight control is as good a method for controlling for confounding as equally tight matching.et al. This is one of over 50 studies, and our paper was not meant to be a comprehensive review of the literature. We are aware of six large cohort studies in addition to our own, all of which had results showing no increase in risk of breast cancer in relation to induced abortion. The contention by Brind and Chinchilli that ‘the overwhelming majority of published studies indicate a positive association between induced…abortion and breast cancer incidence’ is simply false. The reference that they give for this statement is a paper by Brind! A workshop, attended by over 100 expert participants, on Early Reproductive Events and Breast Cancer was sponsored by the US National Cancer Institute, and held in February of this year. A major conclusion from that workshop was that induced abortions do not increase the risk of breast cancer. We believe that this issue has been satisfactorily laid to rest.In their last paragraph, they note that we failed to cite a paper by Howe


Household cleaning and pesticide products may contribute to breast cancer because many contain endocrine disrupting chemicals or mammary gland carcinogens. This population-based case-control study investigated whether use of household cleaners and pesticides increases breast cancer risk.Participants were 787 Cape Cod, Massachusetts, women diagnosed with breast cancer between 1988 and 1995 and 721 controls. Telephone interviews asked about product use, beliefs about breast cancer etiology, and established and suspected breast cancer risk factors. To evaluate potential recall bias, we stratified product-use odds ratios by beliefs about whether chemicals and pollutants contribute to breast cancer; we compared these results with odds ratios for family history  stratified by beliefs about heredity.Breast cancer risk increased two-fold in the highest compared with lowest quartile of self-reported combined cleaning product use  and combined air freshener use . Little association was observed with pesticide use. In stratified analyses, cleaning products odds ratios were more elevated among participants who believed pollutants contribute "a lot" to breast cancer and moved towards the null among the other participants. In comparison, the odds ratio for breast cancer and family history was markedly higher among women who believed that heredity contributes "a lot"  and not elevated among others .Results of this study suggest that cleaning product use contributes to increased breast cancer risk. However, results also highlight the difficulty of distinguishing in retrospective self-report studies between valid associations and the influence of recall bias. Recall bias may influence higher odds ratios for product use among participants who believed that chemicals and pollutants contribute to breast cancer. Alternatively, the influence of experience on beliefs is another explanation, illustrated by the protective odds ratio for family history among women who do not believe heredity contributes "a lot." Because exposure to chemicals from household cleaning products is a biologically plausible cause of breast cancer and avoidable, associations reported here should be further examined prospectively. Pestvo tests . When givo tests -18. Thesvo tests -26. In hvo tests . Taken tNo epidemiological studies we know of have reported on the relationship between cleaning product use and breast cancer, and previous breast cancer studies of pesticides have been largely limited to organochlorine compounds . OrganocTo investigate the relationship between use of cleaning and pesticide products and risk of breast cancer, while considering possible recall bias, we conducted a case-control study of breast cancer and self-reported product use on Cape Cod, Massachusetts, in which we also measured beliefs about breast cancer causation, a possible source of recall bias. Cape Cod is a coastal peninsula where breast cancer incidence has been elevated. Annual female breast cancer incidence in 2002 - 2006 was 151.0 per 100,000 (95% CI 142.6 - 159.8) . The patDetails of the Cape Cod Study have been described previously . BrieflyThe Cape Cod Study expands on a study of breast cancer and tetrachloroethylene (PCE) in drinking water . Cases dFor the present analysis, we excluded 368 cases and 287 controls who were interviewed by proxy, and 10 cases and eight controls who were missing data for one or more key analytic variables. Given that most women for whom we obtained proxy interviews were deceased, excluded women were older, and, consistent with being older, they were less educated. Within the included or excluded groups, cases and controls did not differ demographically, suggesting no selection bias. Exclusions left 787 cases and 721 controls for pesticide analyses. Cleaning product questions were asked only in 1999-2000 interviews, resulting in 413 cases and 403 controls for whom these data were available.We obtained permission to use confidential data from MCR, CMS, and hospitals where cases were diagnosed. The Boston University Institutional Review Board and Massachusetts Department of Public Health Human Research Review Committee approved the study protocol. Participants were asked for informed consent at the outset of interviews.http://silentspring.org/cape-cod-breast-cancer-and-environment-study-survey-instruments.Trained telephone interviewers administered a structured questionnaire on established and hypothesized breast cancer risk factors including family history of breast cancer, menstrual and reproductive history, height, weight, alcohol and tobacco use, physical activity, pharmaceutical hormone use, and education. Information on residential cleaning product and pesticide use was obtained. Participants in 1999-2000 interviews were asked about five categories of cleaning products, including solid and spray air fresheners, surface cleaners, oven cleaners, and mold/mildew products. All participants were asked about use of 10 categories of pesticides in and around their homes, including insecticides, lawn care, herbicides, lice control, insect repellents, and pest control on pets. The 1999-2000 interviews asked about mothballs and treatments for termites and carpenter ants. Participants were first asked if the product was ever used in their home. Participants were then asked to estimate frequency of use using predefined categories. To exclude exposures after diagnosis or index year, participants were asked to report the first and last years of use for pesticides, and use before their diagnosis or index year for cleaning products. At the end of the interview, participants were asked about their beliefs about four factors that may contribute to breast cancer: heredity, diet, chemicals and pollutants in the air or water, and a woman's reproductive or breastfeeding history. Participants were asked whether each contributes to breast cancer "a lot, a little, or not at all." "Don't know" responses were coded. Interview questions can be viewed at a priori consideration of the research design and well-established breast cancer risk factors: age at diagnosis or index year, education, family history of breast cancer in a first degree female relative, breast cancer diagnosis prior to the current diagnosis or index year, and age at first live or still birth (≥ 30 years of age or nulliparous vs. < 30 years of age). Pesticide analyses were adjusted for study (PCE or Cape study). Missing values for family history for 45 (3%) participants were imputed as "no." The percent missing information on family history did not differ between cases and controls. The following potential confounders were evaluated: mammography use, medical radiation, lactation, hormone replacement therapy, oral contraceptive use, diethylstilbestrol exposure, body mass index, smoking, alcohol consumption, teen and adult physical activity, race, marital status, and religion. None of these variables changed the "core"-adjusted odds ratio estimates by ≥ 10%, so they were not included in final models.Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). The following "core" matching variables and potential confounders were included in adjusted odds ratio analyses based on We evaluated ever vs. never use and categorical variables reflecting frequency of use. "Never users" of each product type formed the reference group. If a participant reported ever using a product but the frequency was missing, frequency was imputed as the median for that product. To aggregate "like" exposures, three variables were constructed by summing frequency of use for two types of air fresheners, five types of cleaning products, and eight types of pesticides. Aggregated scores were divided into quartiles based on the distribution of controls. The lowest quartile constituted the reference group. Tests for trends were conducted by modeling ordinal terms for categories of product use or quartiles in the multivariate model.Because participants' awareness of a hypothesis may bias exposure reporting , we evalWeiss  notes thP -value of 0.05 or lower.All analyses were conducted in SAS version 9.1 . Figures were constructed in R software 2.6.1, . Statistical significance was defined by a (two-sided) Study participants were predominantly white (98%), 60-80 years of age (60%) with high school or higher education (94%); more cases (25%) than controls 19%) reported a family history of breast cancer. Characteristics of participants are shown in Table 9% reportPtrend for solid air freshener and mold/mildew control with bleach. Surface and oven cleaners were not associated with breast cancer risk.Breast cancer risk increased approximately two-fold in the highest compared with lowest quartile of combined cleaning product use  and combined air freshener use  (Table Ptrend = 0.05).Combined use of pesticide products was not associated with risk of breast cancer Table . Odds raP < 0.01); 57% of controls and 60% of cases said "chemicals and pollutants in the air or water" contribute "a lot" (P < 0.05).Cases and controls differed significantly in beliefs about the role of heredity and of chemicals and pollutants in breast cancer Table . Among cP = 0.25). In stratified analyses, odds ratios for cleaning products were consistently elevated within the group who said chemicals/pollutants contribute "a lot" to breast cancer, but associations moved towards the null in the other participants Table . For exaSimilarly, odds ratios for pesticides were higher among participants who believed that chemicals/pollutants contribute "a lot" to breast cancer. For example, the odds ratio for most frequent insect repellent use was 2.0  in this belief group compared with 0.8  among others. Pesticide odds ratios stratified by beliefs are shown in Table P < 0.01). The parallel pattern of results for both cleaning products and family history when stratified by relevant beliefs is shown in Figure In addition, a similar pattern was observed in the odds ratios for family history of breast cancer stratified by beliefs about heredity as a cause. The odds ratio for breast cancer and family history was markedly higher among women who believed that heredity contributes "a lot"  and not elevated among others (OR = 0.7, 95% CI: 0.5, 1.1, interaction term Women with the highest combined cleaning product use had two-fold increased breast cancer risk compared to those with the lowest reported use. Use of air fresheners and products for mold and mildew control were associated with increased risk. To our knowledge, this is the first published report on cleaning product use and risk of breast cancer.Some common ingredients of air fresheners and products for mold and mildew have been identified as EDCs or carcinogens, supporting the biological plausibility of the elevated odds ratios we observed ,15,41-51Our results do not corroborate the findings of a Long Island, NY, case-control study . The LonUsing interviews to assess product-related exposures, as we did in this study, has several advantages. It is inexpensive, noninvasive, and integrates exposures over many years and to frequently-occurring chemical mixtures. Currently available biological measures cannot achieve these important characteristics.However, self-reported exposures are subject to multiple sources of error resulting in misclassification. Our questions were cognitively demanding in that they asked participants to report behaviors occurring months to years before. Responses failed to capture use by others, including residues from before the participant moved into the residence; exposures specific to critical periods such as adolescence; exposures outside the home; or all products that contain the chemicals of interest. Although we asked about the first and most recent years of pesticide use, we considered the quality of these data inadequate to evaluate effects of duration of use. Much of the error resulting from limitations in exposure measurement is likely nondifferential, biasing odds ratios toward the null.Self-reports are also vulnerable to bias from differential recall between cases and controls. Women diagnosed with breast cancer may have searched their history for explanations, priming greater recall of product use than for controls. Werler , among oHowever, the family history odds ratios stratified by beliefs suggest another interpretation. The much higher family history odds ratios for women who said heredity contributes "a lot" is unlikely to be primarily due to recall bias, given that self-reporting of first degree family members with breast cancer is generally accurate -66. PrevThe divergent odds ratios in the stratified analysis for family history, which is not likely affected much by recall bias, warns us that the elevated odds ratios for cleaning products should not be too quickly dismissed as resulting from recall bias, since an alternative interpretation is that women's beliefs about disease causation result from their experience. Women who have been intensive product users and are then diagnosed with breast cancer may form the belief that chemicals influenced their risk, or they may be sensitized to news media stories about associations between chemicals and disease and form beliefs from this experience. Social scientists have studied the phenomenon of health beliefs formed from experience in a variety of settings, including the emergence of beliefs about environmental causation among breast cancer activists .Furthermore, the substantial underestimate of risk for family history among women who said heredity does not contribute "a lot" cautions us against limiting product use analyses to a non-belief subgroup as a strategy for dealing with possible recall bias. In addition, the findings of elevated risk for some cleaning products and not others lends evidence that recall bias may not account for elevated risks, even if it contributes in part, since bias would be expected to similarly influence reporting for all the products.Studies that rely on questionnaire data can sometimes assess the validity of self-reported data against another metric, such as chemical concentrations in relevant exposure media. For example, Colt et al.  found siOverall strengths of our study are the population-based design with case identification from the MCR, extensive interviews allowing evaluation of possible confounding by established and hypothesized breast cancer risk factors, and assessment of exposures that extend years before diagnosis and encompass chemicals in use during the past 30 years as well as the more-studied banned organochlorines. Limitations include loss of information due to deaths of women with less treatable cancers. Also, we lack a truly unexposed reference group, limiting contrast in levels of exposure. The self-reported product use exposures have potential for differential and nondifferential error. We did not have adequate numbers to separately evaluate effects in younger women, though some other studies suggest that environmental pollutants may have greater influence on premenopausal disease .To our knowledge, this is the first epidemiological study to suggest an association between cleaning product use, in particular air fresheners and products for mold and mildew control, and elevated breast cancer risk. This association is biologically plausible based on ingredients of these products, such as musks, antimicrobials, and phthalates -49,70-73Laboratory studies have found that many chemicals in home-use pesticides and household cleaning products are mammary gland carcinogens in rodents, influence the proliferation of estrogen-sensitive cells, or affect mammary gland development following prenatal exposure. These findings suggest effects of pesticide and cleaning product use on breast cancer risk, so we undertook a case-control study of breast cancer and self-reported product use. We found increased breast cancer risk among women reporting the highest use of cleaning products and air fresheners. We found little association with home pesticide use. The self-reported product use measures we used have the advantage of integrating exposure over many years to chemical mixtures. However, these measures remain incomplete, likely resulting in nondifferential misclassification, and they are open to recall bias. Investigators sometimes try to avoid the influence of recall bias by limiting analyses to participants who do not subscribe to the study hypothesis, but our results show this may not be a good strategy, given that in our study it would obscure the well-established association between family history and breast cancer risk. In order to avoid possible recall bias, we recommend further study of cleaning products and breast cancer using prospective self-reports and measurements in environmental and biological media.CI: confidence interval; CMS: Centers for Medicare and Medicaid Services; EDCs: endocrine-disrupting compounds; OR: odds ratio; MCR: Massachusetts Cancer Registry; PCE: tetrachloroethylene; Ref: reference; Adj OR: adjusted odds ratio; NY: New York; US: United States.The authors declare that they have no competing interests.ARZ conducted the statistical analyses and led drafting of the manuscript. AA designed and oversaw the PCE Study; contributed to the design, data collection, and epidemiological analysis of the Cape Cod Study; and collaborated on editorial issues. RAR contributed to the design, data collection, and analysis of the Cape Cod Study, particularly with respect to the toxicologic characteristics of exposures, and collaborated in drafting the manuscript. JGB led the design, implementation, and analysis of the Cape Cod Study and collaborated in drafting the manuscript; she conceptualized the comparative analysis of product use and family history odds ratios stratified by beliefs as a strategy for understanding possible response bias. All authors read and approved the final manuscript.


Pinteraction<0.010), but no heterogeneity across ER/PR subtypes.Among the 51 823 postmenopausal women in the Swedish Mammography Cohort, we investigated breast cancer risk in relation to the FFQ-based estimated lignan intake by oestrogen receptor (ER) and progesterone receptor (PR) subtypes. A significant 17% risk reduction for breast cancer overall in the high lignan quartile was observed, especially among PMH user ( Date of breast cancer diagnosis, death, or migration from the study area were identified by linkage of the cohort through the Swedish Registration System. Information about receptor status of breast tumours, measured by an Abbott immunoassay . Statistical tests were two-sided, and significance levels defined as P<0.05.The Swedish Mammography Cohort (SMC) was described previously , the multivariable adjusted relative risks (RR) for the highest quartile (⩾1036 μg day−1) were 0.83  for overall, 0.86 (0.69–1.08) for ER+PR+, 0.77 (0.54–1.09) for ER+PR−, 0.92(0.56–1.52) for ER−PR−. There was no evidence for heterogeneity in the results between the ER+PR+ and other subtypes .Overall, we observed a statistically significant inverse association between lignan intake and breast cancer risk . Compare2), there was no evidence for interaction with lignans in relation to overall risk or of any subtype; all Pvalues for trends were>0.60 and all Pvalues for interaction>0.35. We also observed a significant inverse association of lignans with overall risk among PMH ever-users; the multivariable adjusted RR for the highest quartile of intake compared to the lowest was 46% lower . The observed interaction for PMH use seemed to be confined to ER+PR+ tumors (Pinteraction=0.016). There was no heterogeneity in the results between ER+PR+ and other tumors . Lignans were positively correlated with intake of fruits and vegetables (r=0.4) and of cereal, fruit and vegetable fibre . After adjusting for these factors, the result for lignans was slightly attenuated but still significant among PMH user  but after adjusting for specific fibres, the association among PMH users was still significant. This inverse association agrees with two previous studies among postmenopausal women (In this large population-based prospective cohort of postmenopausal women, we observed a significant inverse association between lignan intake and overall breast cancer risk, especially among PMH user. There was no evidence of heterogeneity across ER/PR tumours. These results are similar to our previous study with a significant inverse association between cereal fibre and breast cancer risk among PMH users (CYP17 (in vitro studies also showed that lignan ENL in the presence of oestrogens suppressed the oestrogen-induced proliferation in MCF-7 breast cancer cell (An inverse association of lignans with risk has been reported among premenopausal women (CYP17 . The poscer cell  and stimThe lack of association among overweight women may be due to the relatively high circulating oestrogen levels from PMH use having a stronger effect than the endogenous oestrogens formed in peripheral tissues (Our finding for ER+PR+ tumours among PMH users partly agrees with a prospective study (


P for trend=0.02).In a prospective study of 694 657 parous women in Norway, 5474 developed breast cancer after their first birth. If the first pregnancy lasted less than 32 weeks, the risk was 22%  greater than after a pregnancy of 40 weeks or more, with a significant declining trend in risk  87, 289–290. doi:10.1038/sj.bjc.6600453www.bjcancer.comCancer Research UK© 2002  Pregnancies generally convey protection against breast cancer, and the degree of protection depends on the woman's age at childbearing . It has In this study we have combined information from two nationwide health registries in Norway in order to examine whether length of gestation is related to breast cancer risk. Data were derived from the Medical Birth Registry that comprises all births since 1967, and the Norwegian Cancer Registry, which has registered incident cancers since 1953. Midwives and doctors have to fill in a standardised form to notify the Birth Registry about each birth that takes place in the country, and the reporting of new cancers to the Cancer Registry is also mandatory. Length of gestation, based on the last menstrual period, was recorded in more than 90% of all pregnancies, and included pregnancies lasting from 154 to more than 300 days of gestation. In the analysis, length of gestation was categorised into four separate categories.We used the unique national identification number to link women registered at the Medical Birth Registry and the national Cancer Registry to identify women who had developed breast cancer subsequent to giving birth. A total of 695 873 women had been registered with a first pregnancy between 1967 and the end of 1998, for whom length of gestation and infant birth weight had been recorded. Of those, 1216 were excluded from analysis, either because they had a diagnosis of cancer recorded prior to their first birth, or because they had emigrated and could not be traced. Thus, we have followed 694 657 women from their first birth in 1967 or later until the diagnosis of cancer, death from any cause, or to the end of follow-up , whichever occurred first. We examined whether breast cancer risk differed between women who had different length of gestation in their first pregnancy. In the analysis, we adjusted for attained age (nine categories), calendar period of diagnosis (three categories), age at first birth (five categories), and number of subsequent births (five categories), using Poisson regression modelling .P for trend=0.02).We found, as expected (Table 1This large prospective study is based on linkage between reliable data from two established national registries , and it


Prior pregnancy is known to protect against development of breast cancer. Recent studies have demonstrated that pregnancy has the capacity to establish small numbers of immunologically active fetal-derived cells in the mother, a phenomenon known as fetal microchimerism (FMc). We asked whether presence of FMc, routinely acquired during pregnancy, is a protective factor for breast cancer.6 maternal genomes in controls and cases, respectively.DNA extracts from peripheral blood specimens were obtained from a population-based case-control study of risk factors for breast cancer in women 21 to 45 years old. Specimens were tested with quantitative PCR for presence and concentrations of male DNA presumed to derive from prior pregnancies with a male fetus. Odds ratios (OR) and 95% confidence intervals (CI) were estimated with consideration of multiple established reproductive and environmental risk factors for breast cancer. FMc results were generated on 99 parous women, 54 with primary invasive breast cancer and 45 general population controls. FMc prevalence was 56% (25/45) and 26% (14/54) in controls and cases, respectively. Women harboring FMc were less likely to have had breast cancer . In addition, FMc concentrations were higher in controls versus cases (p = 0.01). Median concentrations were 2 (0–78) and 0 (0–374) fetal genomes/10Results suggest that the enigma of why some parous women are not afforded protection from breast cancer by pregnancy might in part be explained by differences in FMc. Mechanistic studies of FMc-derived protection against breast cancer are warranted. Risk modifiers for development of breast cancer are both genetic and environmental. The known germline genetic risk modifiers identified thus far are few  and overall account for only 2–10% of all cases We and others have shown that a natural consequence of normal pregnancy is the acquisition and stable persistence of small numbers of fetal cells in the mother's body, a phenomena known as fetal microchimerism (FMc) Specimens tested for FMc were obtained from women residing in the three county Puget Sound region of Western Washington State who previously participated in a population-based case-control study of breast cancer in women aged 21–44. The methods for this study have been described For the current study, 100 participants were tested for FMc. One woman was excluded from final analysis because correlative clinical data for reproductive factors was not available. Altogether, 54 cases and 45 controls were evaluable for FMc.DYS14. Male DNA is assumed to derive from prior pregnancy with a male fetus. The approach permitted comparison of cases to controls while recognizing that the overall prevalence of FMc is underestimated as FMc from female fetuses could not be assessed. The method for testing male FMc using quantitative PCR has been previously described DYS14. Quantitative PCR reactions were performed on an ABI Prism 7000 running the manufacturer's software (SDS v1.2.3). Results from each aliquot were plotted by the software onto a simultaneously run calibration curve generated from known quantities of DYS14. An additional 2 aliquots from each specimen were tested for the beta-globin gene (present in two copies per cell) with results plotted similarly on a beta-globin calibration curve to provide an estimate of the total number of cells tested. After using a correction factor of 6.6pg of DNA per cell 6 host  genome equivalents. A minimum of 3.0×104 genomes were tested in all 6 wells combined to insure sufficient material was examined for FMc. A maximum of 3.0×104 genomes were tested in any single well because of PCR inhibition when greater input DNA is used. All wells read positive for DYS14 sequence by the software were confirmed by individual amplification analysis in a blinded manner by one of the authors (VKG). For a specimen to be considered positive for FMc, a minimum of two wells were required to have surpassed the detection threshold for amplification.FMc was identified and quantified in genomic DNA extracted from peripheral blood buffy coat specimens employing quantitative PCR for a Y chromosome specific gene, The primary outcome for analysis was disease status (breast cancer case vs. control) and the principal predictor of interest was the presence of FMc. Factors examined as potential confounders or effect modifiers included age , age at first birth, number of children, birth of a son, history of breastfeeding, miscarriage, abortion, oral contraceptive use, smoking status, age at menarche and number of cell equivalents tested for detection of FMc. A factor was defined as a confounder if there was a discrepancy of 10% or more in the estimated coefficient of interest between the multivariable model including the factor and the model without it. Differences in subject characteristics between groups were assessed via t-test for continuous variables and Chi-squared test for categorical factors. Logistic regression models were used to estimate the association between presence of FMc and disease status, while adjusting for age and other confounding factors.FMc concentrations were further analyzed according to disease status. FMc concentrations were ranked and the ranks were used as the outcome for linear regression models to account for departures from normality in the distribution of the FMc values. Such transformation of the data preserves the ordering of values and gives estimates that are less sensitive to outlying values; however, model coefficients are no longer interpretable in terms of actual FMc values. The linear regression models were adjusted for age and other confounders.Additional analyses were conducted to examine whether breast cancer-specific features were associated with FMc prevalence among the cases. Presence of FMc was treated as a binary outcome in logistic regression models, with age at diagnosis and various disease characteristics as the predictors. P-values from regression models were derived from the Wald test, and no adjustments were made for multiple comparisons. Analyses were performed on SAS software version 8 .Baseline characteristics of breast cancer patients and control participants are shown in 4) in controls versus 5.6×104 (95% CI 4.9–6.3×104) in cases). This factor acted as a moderate confounder, slightly diminishing the effect of FMc in the final model .Overall, FMc was found in 39 women, including 25 of 45 controls (56%) and 14 of 54 breast cancer patients (26%). Concentrations of FMc in peripheral blood in women with and without breast cancer are depicted in Among cases, analyses were conducted to examine whether breast cancer specific features were associated with FMc prevalence . The resIn this case-control study of breast cancer among parous women, women with breast cancer were more frequently deficient in FMc when compared to control women. Both overall prevalence and quantity of FMc were significantly different between parous women with and without breast cancer. Other known risk modifiers for breast cancer such as age at first pregnancy, history of oral contraceptive use, breast feeding, and smoking did not meaningfully confound the overall association of FMc absence with breast cancer. Furthermore, in case-only analyses, women with adverse breast cancer features  consistently had lower prevalence of FMc although no single characteristic reached statistical significance because power was limited for such analyses.In prior pilot studies we similarly found a decreased prevalence of FMc in women with breast cancer When comparing the current data to prior studies of FMc, some additional differences merit discussion. FMc results could vary depending on the compartment of blood tested. Most prior studies of FMc examined Ficoll-purified peripheral blood mononuclear cells. To our knowledge, there are no studies of FMc in buffy coat. The overall prevalence and concentrations of FMc in controls described here were somewhat higher when compared to findings from Ficoll-purified cells. The key constituents more greatly represented in buffy coat compared to Ficoll-purified cells are large granular cells such as neutrophils or dendritic cells. Our data then indirectly suggest that FMc in healthy women might be represented in cells that are part of the innate immune response and/or in cells involved in antigen presentation. Second, in prior work, we have been able to employ an extensive panel of allelic quantitative PCR assays to catalog all potential sources of FMc regardless of sex of the child The protection from breast cancer afforded by parity is incomplete. We provide data that suggest there is a failure to acquire or maintain allogeneic immune cells (FMc) transmitted from the fetus to the mother during pregnancy in women who develop breast cancer. These allogeneic cells have the potential to participate in immune surveillance for breast or other cancers as observed in clinical hematopoietic stem cell transplantation. Additional studies are required to identify the specific mechanisms by which FMc could participate in the protection from breast or other cancers. Knowledge gained from mechanistic studies may contribute to the design of allogeneic vaccine-based or adoptive immunotherapy for breast cancer. We acknowledge that replication of our findings in larger study populations is required because the sample size is small. Nonetheless, if our results are replicated, testing for FMc could be used to identify healthy women who might be at risk for developing breast cancer. Finally, the work presented here is of potential interest to evolutionary biologists as it provides additional support in human females for the concept of long-term fitness benefit through reproduction.


Because treatment for breast cancer may adversely affect skeletal metabolism, we investigated vertebral fracture risk in women with non-metastatic breast cancer. The prevalence of vertebral fracture was similar in women at the time of first diagnosis to that in an age-matched sample of the general population. The incidence of vertebral fracture, however, was nearly five times greater than normal in women from the time of first diagnosis , and 20-fold higher in women with soft-tissue metastases without evidence of skeletal metastases . We conclude that vertebral fracture risk is markedly increased in women with breast cancer. © 1999 Cancer Research Campaign


The role of fried foods on laryngeal cancer risk was investigated in a case–control study from Italy and Switzerland on 527 cases and 1297 hospital controls. A significant increased risk was found for high consumption of fried meat, fish, eggs and potatoes, with odds ratios of 1.6, 3.1, 1.9 and 1.9, respectively.British Journal of Cancer (2002) 87, 1230–1233. doi:10.1038/sj.bjc.6600639www.bjcancer.com© 2002 Cancer Research UK The relation between cooking methods such as frying, boiling and barbecuing and cancer risk has been inadequately investigated in epidemiological studies  are produced, particularly when cooking temperature is very high . Fried fThe larynx is directly exposed to volatile carcinogens in tobacco smoking. Besides tobacco and alcohol consumption, which are the main recognised risk factors, diet has been associated with laryngeal cancer risk . HoweverWe have therefore investigated the possible relation between fried food intake and laryngeal cancer risk using data from a large case–control study conducted in Italy and Switzerland, which reported a protective effect of vegetables, fruit, and olive oil and a detrimental effect of meat and other protein rich foods  and in the Swiss Canton of Vaud  was investigated through an interview-administered food freqeuncy questionnaire (FFQ), previously tested for validity (Odds ratios (OR) and the corresponding 95% confidence intervals (CI) for each category of intake of fried foods  were estimated using unconditional multiple logistic regression models . All modTable 1−2).Table 2Our study suggests that consumption of fried foods is directly related to the risk of laryngeal cancer. A similar finding has been reported in another study which considered fried meat in relation to cancer of the larynx  seed oils, frequently used for frying, have been shown in our dataset to be positively related to laryngeal cancer risk . HoweverThe hospital-based setting is a potential limitation of our study, since hospital controls may not be comparable with cases. However, controls were selected among patients with admission diagnosis not related to tobacco smoking, alcohol drinking and diet modifications. Moreover, in order to reduce any information bias, the questionnaire was administered to both cases and controls by the same interviewers and under similar conditions, and the food frequency intake for subjects interviewed at home was well comparable with that obtained at hospital (The high participation rate of cases and controls, the comparable catchment areas of study subjects, the careful adjustment for tobacco and alcohol, as well as other potential confounding factors, are among the strengths of the study. Moreover, the use of FFQ, reported to be satisfactorily valid .In conclusion, our analysis suggests that the consumption of fried foods, irrespective of the content of foods, might be associated with an excess in laryngeal cancer risk. Selection, information bias or confounding are unlikely to explain this association, and its strength indicates that it is unlikely to be due to chance alone. In the absence of simple biological mechanisms, it is however unclear whether this implies causation, or a non-specific association with a poorer diet (


Limited evidence suggests that people from non-English speaking backgrounds in Australia have lower than average rates of participation in cancer screening programs. The objective of this study was to examine the distribution of bowel, breast and prostate cancer test use by place of birth and years since migration in a large population-based cohort study in Australia.In 2006, screening status, country of birth and other demographic and health related factors were ascertained by self-completed questionnaire among 31,401  participants aged 50 or over from the 45 and Up Study in New South Wales.35% of women and 39% of men reported having a bowel cancer test and 57% of men reported having a prostate specific antigen (PSA) test, in the previous 5 years. 72% of women reported having screening mammography in the previous 2 years. Compared to Australian-born women, women from East Asia, Southeast Asia, Continental Western Europe, and North Africa/Middle East had significantly lower rates of bowel testing, with odds ratios  ranging from 0.5 (0.4–0.7) to 0.7 (0.6–0.9); migrants from East Asia  and North Africa/Middle East  had significantly lower rates of mammography. Compared to Australian-born men, bowel cancer testing was significantly lower among men from all regions of Asia  and Continental Europe . Only men from East Asia had significantly lower PSA testing rates than Australian-born men . As the number of years lived in Australia increased, cancer test use among migrants approached Australian-born rates.Certain migrant groups within the population may require targeted intervention to improve their uptake of cancer screening, particularly screening for bowel cancer. In New South Wales (NSW), Australia's most populous state, 31% of the population aged 45 years or older in 2006 were born outside of Australia [) [The 45 and Up Study is a population-based cohort study of people aged 45 and over in NSW Particip) . The parThe 45 and Up Study has been approved by the University of New South Wales Human Research Ethics Committee and the Cancer Council New South Wales Ethics Committee.A self reported history of bowel and breast cancer screening was ascertained from the questions, "Have you ever been screened for colorectal (bowel) cancer/been for a breast screening mammogram?". History of PSA testing was ascertained from the question, "Have you ever had a blood test ordered by your doctor to check for prostate disease? (PSA test)". Respondents were also asked to indicate how long ago (in years) they had used each test type.Participants reporting a personal history of bowel cancer were excluded from bowel screening analyses as these individuals would be undergoing more frequent surveillance. Likewise, analyses of breast screening excluded women who reported a history of breast cancer and analyses of PSA testing excluded men with a personal history of prostate cancer.Place of birth was grouped according to a modified version of that used in the Global Burden of Disease Study   and regiOdds ratios and 95% confidence intervals for being tested for each type of cancer by migrant factors were estimated using logistic regression. Each model was stratified by gender and adjusted for age , highest level of education achieved , family history of relevant cancer type , private health insurance status (yes/no) and place of residence (ARIA+ 2001). The final models did not include place of residence because it made no difference to the odds ratios. Years lived in Australia for migrants was analysed as a continuous variable with an additional adjustment for place of birth. All models included a 'missing/unknown' level for each covariate.Of those in the cohort aged 50 years or over, 26.0% of men and 22.5% of women were migrants (24.2% of the cohort). The distribution of demographic factors by place of birth for men and women are shown in Tables one and two, respectively in Additional file 1Of the 15,275 men aged 50 years or over, 1,090 reported having been diagnosed with prostate cancer and were excluded from analyses on PSA testing. 322 men reported ever having bowel cancer and were excluded from analyses on bowel cancer testing. Of the 16,126 women aged 50 years or over, 226 reported a previous diagnosis of bowel cancer and were excluded from analyses on bowel cancer testing and 966 women reported a previous diagnosis of breast cancer and were excluded from analyses on mammography.Table three in Additional file p = 0.003) with every 10 years lived in Australia, yet remained lower than the Australian-born rate irrespective of years lived in Australia.After adjusting for age, education, family history of cancer and health insurance status, there was significant variation in the use of bowel cancer tests across migrant groups. Men from Oceania , East Asia , Southeast Asia , South and Central Asia , Continental Western Europe , Central and East Europe  and the Middle East/North Africa  reported lower levels of bowel test use than Australian-born participants  with every 10 years lived in Australia. Language spoken at home was associated with reduced use of PSA tests .There was variation in PSA test use by place of birth Figure , howeverp = 0.001), reaching the Australian born rate after around 35 years of living in Australia. Women who spoke a language other than English at home were less likely to report a bowel screening test than those who spoke only English .Women born in East Asia , Southeast Asia , Continental Western Europe  and the Middle East/North Africa  were significantly less likely to report having a test for bowel cancer within the previous 5 years than Australian-born women . Language spoken at home was associated with reduced use of mammograms .There was significant variation in mammography use by place of birth Figure  however We found that within a large cohort of people aged 50 years and over in Australia, there is variation in the use of tests for bowel, breast and prostate cancer both within and between migrant groups. The odds of bowel cancer test use  among participants from non-English speaking backgrounds (primarily Asia and Europe) was significantly lower than Australian-born participants. Indeed, for participants who reported speaking a language other than English at home, the odds of reporting a test for bowel cancer within the previous 5 years was up to 40% lower than for English-only speakers. In contrast, mammography use among women and PSA test use among men, did not vary widely by migrant group. The odds of reporting a mammogram for women born in East Asia and North Africa/Middle East were half those for Australian-born women, and the odds of a man born in East Asia reporting a PSA test were reduced by 60%. Use of bowel and PSA tests by migrants increased with increasing number of years lived in Australia, taking about three decades to approach Australian born rates.In Australia, a freely available program for bowel cancer screening had not begun at the time of this survey so it is not surprising that bowel cancer test use overall is lower than mammography and PSA test use. Free population screening for breast cancer has been offered to women aged 50–69 since 1992 and has been widely advocated. PSA testing, while not currently recommended as a population-based screening tool for prostate cancer, is subsidised by the government and has had considerable media attention ,12.Among women, mammography use did not vary by migrant group as much as bowel test use among women. Nevertheless, women from East Asia and the Middle East/North Africa were significantly less likely than Australian-born women to have had a mammogram within the previous two years and these groups of women make up a substantial proportion of the Australian population (i.e. 11% of the NSW population were born in Asia and the Middle East/North Africa) -16, and Among men, reported PSA test use did not vary widely by migrant group. Only men from East Asia reported significantly lower PSA test use than Australian-born men. Ethnic variation in PSA test use among migrant groups to the USA have been reported ,18. PsycBowel cancer testing was significantly lower among migrants from non-English speaking backgrounds than for Australian-born participants. Among cultures in Asia, Oceania, North Africa and the Middle East there may be a lack of awareness about bowel cancer in general. Bowel cancer incidence and mortality rates in Asia are much lower than in Australia , and so Overall, our results suggest that barriers to bowel cancer screening arising from not having a freely available and accessible program appear to have affected migrants from non-English speaking backgrounds to a greater extent than Australian-born people. However, low rates of participation among those from non-English speaking backgrounds were also reported in the freely available National Bowel Cancer Screening Pilot, suggesting that factors other than cost and accessibility are barriers to participation among these groups . EvidencAcross all the test types examined here, one group that displayed consistently low rates of cancer screening was participants from East Asia. It is possible that this group of people under-utilise health services in general. Cultural rather than demographic factors are the likely cause of this, as participants from East Asia were in the target age group for cancer screening (50–59 years), were generally well educated , primarily lived in major cities, and a high proportion had private health insurance. These factors are usually associated with high participation in cancer screening programs . One majOur finding that cancer screening among migrants increases with the number of years since migration has also been reported in studies elsewhere ,30,31, aCancer screening history in this study was derived from self-report. A meta-analysis of validation studies on self-reported cancer screening use in the USA found that self-reported versus documented history of screening had reasonably high sensitivity  and specificity  . HoweverCohort study participants tend to be healthier and more health conscious than non-participants ; hence, NSW has one of the most heterogeneous populations in the world, with almost a third of those aged 45 and over having migrated to Australia. The 45 and Up Study is the largest cohort study in NSW and the results presented here describe significant variation in the use of three cancer screening paradigms across a diverse range of migrant groups using uniform outcome measures. The 45 and Up study also allowed adjustment for important demographic factors related to screening use, as well as family history of cancer and access to health services. Further, this is the first Australian study, and the biggest internationally, to describe PSA test use across different cultural groups.It is of general concern that many migrants from non-English speaking backgrounds are less likely to have bowel or breast cancer screening tests than participants who were born locally. Differences in cancer screening use between migrants and locally-born participants were particularly marked for bowel screening test use. However, there is potential for FOBT rates to match those of mammography and PSA testing and so it will be interesting to monitor trends in screening participation within the cohort as the National Bowel Cancer Screening Program becomes more widely available.The authors declare that they have no competing interests.Study conception and design: Weber, Banks, Sitas. Drafting the manuscript: Weber, Banks. Statistical analysis and interpretation: Weber, O'Connell, Banks. Revision of the manuscript for important intellectual content: Sitas, O'Connell, Smith. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:Weber Tables. Contains Tables 1 – 3.Click here for file


P for trend, 0.28). Stratified analyses showed that the inverse association was restricted primarily among women who had a high body mass index (BMI), with an adjusted OR of 0.30 (95% CI = 0.10–0.94) observed for the highest intake group. The reduction in risk was stronger for breast cancer positive for both oestrogen receptor (ER) and progesterone receptor (PR)  than those with other ER/PR status. More pronounced inverse associations were observed in analyses among those who reported no recent change in soyfood intake than those conducted in all subjects. A dose–response relation between soyfood intake and breast cancer risk was observed in this subset of women , with an OR of 0.46 (95%CI = 0.28–0.75) for those in the highest decile intake group. No clear monotonic dose–response relation was found between soyfood intake and breast cancer risk among regular soy eaters, but nevertheless the results suggest that regular soyfood consumption may reduce the risk of breast cancer, particularly for those positive for ER and PR; the effect may be modified by body mass index. © 2001 Cancer Research Campaign http://www.bjcancer.comWe evaluated the association of soyfood intake and breast cancer risk in a population-based case–control study among Chinese women in Shanghai. Included in the study were 1459 cases and 1556 age-matched controls, with respective response rates of 91.1% and 90.3%. Usual soyfood intake was assessed using a food frequency questionnaire (FFQ). Separate analyses were performed for all subjects and for the subset who reported no recent change in soyfood intake. The intake levels of soyfoods among women in Shanghai are high, with 96.6% women reporting soyfood consumption at least once a week. A statistically non-significant reduced risk (odds ratio (OR) = 0.78 95% CI = 0.52–1.16) of breast cancer was observed among those who reported eating soyfood at least once a week. Compared to those in the lowest decile intake group, women in the highest decile intake group had a 30% reduced risk of breast cancer , but no monotonic dose–response relation was observed (


Women with a family history of breast cancer may be at higher risk for breast cancer, but few previous studies evaluating diet and breast cancer have focused on such women. The objective of the present study was to determine whether diet, a modifiable risk factor, is related to breast density among women at high genetic risk for breast cancer.Women with at least one first-degree or second-degree relative with breast cancer or ovarian cancer participating in the Fox Chase Cancer Center Family Risk Assessment Program completed health history and food frequency questionnaires and received standard screening mammograms. Cranial–caudal mammographic images were classified into the four Breast Imaging Reporting and Data System categories ranging from 'entirely fatty' to 'extremely dense'. Logistic regression analysis using proportional odds models for polychotomous outcomes provided estimates of odds ratios for having a higher category versus a lower category of breast density.Among 157 high-risk women, breast density was inversely associated with vitamin D intake . In contrast, intakes above the median level for protein  and above the median level for animal protein  were associated with higher breast density, but only among women whose family history did not reflect a known familial cancer syndrome or a breast cancer predisposition gene.For women with a strong family history that was not associated with known cancer syndromes, dietary factors may be associated with breast density, a strong predictor of breast cancer risk. Since women with strong family history are often very motivated to change their lifestyle habits, further studies are needed to confirm whether changes in diet will change the breast density and the subsequent onset of breast cancer in these women. Women with a family history of breast cancer may be at higher genetic risk for breast cancer because of either recognized deleterious mutations or as yet unidentified low-penetrance alleles. Such women are likely to be especially motivated to modify their lifestyle to reduce their risk for breast cancer. Diet modification is one possible strategy, but few previous studies evaluating diet and breast cancer have focused on women at high genetic risk ,2.Breast density, the percentage of total breast area with a mammographically dense appearance, is an informative marker for breast cancer risk because of its strong association with breast cancer -5. BreasThe study sample was drawn from 1,313 women enrolled in the Family Risk Assessment Program (FRAP) at Fox Chase Cancer Center in Philadelphia from September 1991 to April 2001. The FRAP was initiated in 1991 to offer education and preventive interventions, and to serve as a research base for studying gene–environment interactions in breast cancer and ovarian cancer. Women are eligible for the FRAP if they have at least one first-degree or second-degree relative with breast cancer or ovarian cancer. Recruitment strategies include referrals from breast cancer patients or ovarian cancer patients at Fox Chase Cancer Center, radio and newspaper advertisements, and physician referrals and self-referrals.n = 7), because their mammograms could not be obtained (n = 5), or because they reported an energy intake >3,500 kcal/day (n = 1) – leaving 164 for inclusion in analyses. A comparison of the women included in the analysis with remaining women in the participant pool showed no significant differences in age, ethnicity, level of education, body mass index, dietary intake, or smoking status, but participants were more likely than nonparticipants to have a first-degree relative with breast cancer .FRAP participants were eligible for the breast density study if they were at least 40 years old. Exclusion criteria included a history of breast augmentation or reduction, a history of prophylactic mastectomy, a history of cancer except nonmelanoma skin cancer, a current or planned pregnancy, current breastfeeding, a weight change of at least 20 lb during the past year, a substantial change in diet over the past year, or no mammogram planned within the study timeframe. Of 510 potentially eligible women invited to participate, 177 women agreed, 153 women declined, 125 women could not be contacted, and 55 women were subsequently found to be ineligible. An additional 13 women were excluded – because their questionnaires were inadequately completed  sporadic, indicated by a single occurrence of cancer diagnosed at any age occurring on one side of the family only; (2) familial, reflecting a pattern of cancers seen in at least one generation but not fitting a known cancer family syndrome; (3) putative hereditary, fitting a hereditary pattern of cancer inheritance or known cancer family syndrome not yet confirmed by genetic testing; or (4) confirmed hereditary, representing inheritance of a cancer predisposition gene confirmed through genetic testing performed on the proband or on a relative. Women in the putative and confirmed hereditary categories (categories (3) and (4)) were grouped together in analyses to reflect the presence of a cancer family syndrome whether based on pedigree analysis or genetic testing. Such pedigrees primarily reflected the presence of a BRCA1 or BRCA2 mutation but also included other cancer family syndromes such as Li–Fraumeni syndrome or Cowden's disease.All FRAP participants were also asked to complete the Harvard Diet Assessment Form  for infoParticipants in the breast density study received a standard screening mammogram at Fox Chase Cancer Center, were measured for weight and height, completed another Diet Assessment Form for their dietary intake for the year previous to the study mammogram, and completed an additional questionnaire for updated information on smoking habits, physical activity, and reproductive factors including pregnancies, breastfeeding, use of hormonal contraceptives or hormone replacement medicine, age at first live birth, and menopausal status. Menopausal status was determined based on whether the participant reported having had a menstrual period within the last year. The study protocol was approved by the Institutional Review Board of the Fox Chase Cancer Center (IRB protocol number 00-803), and all participants gave their written informed consent to participate in the study.All participants received a standard screening mammogram. For premenopausal women, all efforts were made to schedule mammograms during the follicular phase of each woman's menstrual cycle, when breast tissue is less radiographically dense . Breast r = 0.97) in the 172 women with mammographic data, and assessments between left and right sides agreed in all but 10 (6%) women. In reproducibility assessments conducted in a randomly selected set of 52 images, we calculated a kappa statistic of 0.97 for the left-side images and 0.89 for the right-side images.Results presented below are based on radiological classifications for the cranial–caudal view of a randomly selected side. Consistent with previous work , howeverWe used logistic regression analysis for polychotomous outcomes using proportional odds models  to estimFinal multivariate models included 157 women with complete covariate data and adjusted for age, body mass index, caloric intake, age at menarche, menopausal status, history of hormone replacement therapy use, and family history category. Results were not materially different when we excluded six women who reported current use of either raloxifene or tamoxifen. Because detailed questions on pregnancy history were not included in the baseline questionnaire until 1996, a large number of women had incomplete data on number of live births and age at first live birth. We therefore ran separate models to examine potential confounding by these factors in the subset of women with complete data for these variables.P values for a linear trend were obtained for each dietary variable using an ordinal variable representing the scaled median value for each tertile. We examined effect modification by menopausal status using stratified models with each dietary variable dichotomized at the median. The P values for interaction were obtained from a model including all women, with a dietary variable x menopausal status interaction term. Because we observed no significant differences in effect estimates by menopausal status, results presented are for premenopausal women and postmenopausal women combined. We used a similar strategy to examine effect modification by family history category, comparing women with a hereditary family history of cancer with women without such a family history. We combined women with sporadic breast cancer family histories and women with familial breast cancer family histories because there were too few women (n = 32) with only a family history of sporadic breast cancer. In contrast to women with a hereditary family history of cancer based on pedigrees or genetic testing representing a stronger genetic predisposition to breast cancer, women with sporadic breast cancer family histories and familial breast cancer family histories may represent women with lower-penetrance susceptibility genes that have not yet been identified, but that still places them at higher genetic risk.The n = 20) were classified as entirely fatty, 28.0% (n = 44) as having scattered fibroglandular tissue, 34.4% (n = 54) as heterogeneously dense, and 24.8% (n = 39) as extremely dense. Having denser breasts was associated with younger age, lower body mass index, older age at menarche, smaller number of live births, older age at first live birth, and a history of having used hormone replacement therapy . Breast density was not associated with any other nutrients of interest .Previous studies have observed a protective effect of folate against breast cancer , possiblDifficulties in assessing breast density may contribute to the inconsistent results of studies on diet and breast density. Most studies, including the current analysis, defined breast density in categories of percentage density. While the method is more subjective than a computer-assisted method , the BreThe relevant time period of exposure is also unclear. Women randomized to a low-fat, high-carbohydrate diet for 2 years as part of the Canadian Diet and Breast Cancer Prevention Study Group experienced a greater decrease in area of breast density relative to a nonintervention group ,11, suggA limitation of the present study is its relatively small sample size, which limited our ability to detect significant associations and effect modification by menopausal status. Our sample is unique, however, in that all women had a family history of breast cancer. Moreover, over 40% of them had a family history indicating the presence of a high-penetrance cancer predisposition gene, or had been tested to confirm it.Examining only the recent diet may additionally have limited our ability to evaluate the role of dietary intake in relation to breast density. Findings were not different when we used the average value of dietary intake reported at enrollment into the FRAP and that reported for the current breast density study, with a median time interval between the two administrations of 4.5 years, but no other dietary information was available to assess effects of longer-term dietary intake on breast density. Data were incomplete for the number of live births and for age at first live birth; but despite their significant associations with breast density, these two variables were not important confounders among the 120 women not missing this information.Our findings may be biased if a woman's knowledge of her breast density, or some characteristic related to her breast density, influenced her reporting of her dietary intake, or changed her intake so that her current report was not reflective of her long-term diet. For example, women with higher breast density may have been more likely to perceive themselves at higher risk for breast cancer and to modify their diets accordingly. We saw no differences, however, in either breast density or dietary intake by perception of risk for breast cancer reported at baseline (results not shown).Because of the large number of dietary factors explored in this analysis, our findings should be interpreted with caution, warrant further investigation into the etiologic mechanism and warrant confirmation in larger hypothesis-based and pathway-based studies.Finally, our findings may be limited in their ability to be generalized to other populations. Participants were drawn from participants in a high-risk program, and, even among these women, those with a lesser family history of breast cancer were underrepresented in our sample. Nevertheless, the availability of detailed pedigrees is a significant strength of the study as it allowed us to classify women on the basis of their family history of breast cancer in more detail than has been conducted previously, and hence to distinguish women at the highest genetic risk for breast cancer. Our study offers suggestive findings that should be confirmed in a larger sample representing a range of genetic and familial risk for breast cancer, in order to clarify the extent to which diet differences might be related to breast density, and whether effects differ by genetic susceptibility. Future studies might extend these findings to see whether changes in dietary intake would be associated with a change in breast density and a subsequent change in breast cancer risk.In summary, in the present broad exploration of dietary factors in women enrolled in a high-risk program for breast cancer, we found that only vitamin D intake was inversely associated with breast density. Protein and animal protein intake were positively associated with breast density, but only among women without a hereditary family history of breast cancer. Our latter, tentative finding suggests that some dietary modification strategies may be more effective in reducing breast density and hence breast cancer risk in women with a family history of breast cancer suggestive of lower-penetrance susceptibility genes, but this requires confirmation in a larger sample representing a range of genetic risks for breast cancer.FRAP = Family Risk Assessment Program.The authors declare that they have no competing interests.MT initiated the research project, conducted the statistical analyses, and drafted the manuscript. CB provided input on subsequent revisions of the manuscript. KAE conducted the qualitative breast density assessments. MBD is the Principal Investigator for the FRAP, contributed to the design of this study, and provided input on the manuscript. All authors read and approved the final manuscript.


Sir,I was delighted to read your recent electronic publication of the study concerning early onset of breast cancer in a group of British black women by Trinidad, an island in the southern most part of the Caribbean Sea, adjacent to South America, has a population with a diverse racial mixture, similar to Hackney. The principle ethnic groups in Trinidad are African (43%) and Eastern Indian (41%), which account for most of the population. These two ethnic groups are fourth generations of slaves brought to Trinidad in the late 1800s to work in the plantations. Breast cancer is the most prevalent carcinoma amongst women in Trinidad.We found that Afro-Caribbeans were the most commonly affected race (54%) followed by Indo-Caribbeans (35%) then the mixed-race group (11%). The average age of the patients and ranges are as follows: Afro-Caribbean average age 53 years (range 28–89 years), Indo-Caribbean average age 55 years (range 29–76 years) and mixed race average age 59 years (range 29–80 years).et al on blacks and whites, showed that Afro-Caribbeans were almost twice as likely to develop intraductal or intralobular carcinoma compared to the Indian-Caribbean population of Trinidad. We found no differences between our groups with respect to age of presentation as Bowen et al.Our study, similar to study of Bowen We also analysed benign breast lumps between the same ethnic groups and found no significant differences but confirmed that fiboadenoma is the commonest benign breast lump, which occurs principally in young women (It is well documented in the literature, mostly from United States, that African-American women have a worse breast cancer survival rate and a significantly younger age of diagnosis, such as in a large study of 135 000 women by The questions that I would like to raise are regarding clarification of the heritage of the black women included in this study. Were they African or West Indian, and were the white women born in England or were they Jewish or Eastern European. Were mixed-race women included in the study or excluded. The importance of original heritage is highlighted in a study by et al. et al due to ethnicity or confounding parity.Lastly, I am interested to know if data concerning the parity and age of first full-term pregnancy were recorded by Bowen I think this study was worthwhile but the real question is how will these findings that black women get breast cancer at a younger age and are twice as likely to die of the disease than white women be incorporated into the UK breast-screening programme. There is also a need to study other ethnic groups because UK has a vast multi-cultural population and there are ethic variations with other types of carcinomas.


Current Medical Research and Opinion. The new findings add to the evidence that breast cancer risk is higher in urban settings and may eventuate in new breast cancer screening guidelines.Epidemiologic studies have found differences between urban and rural women in breast cancer incidence and mortality, both generally being higher in urban areas. Now a British study suggests that women who live or work in urban areas have denser breasts and thus potentially a greater risk of breast cancer, according to a report published online 19 December 2007 ahead of print in Cancer Epidemiology, Biomarkers & Prevention concluded that women with high breast density have a nearly 5-fold higher breast cancer risk than women with the lowest breast density.Breasts are made up of glandular and fatty tissue. Glandular tissue is denser than fatty tissue and harder to read on a mammogram; a higher percentage of dense tissue is also linked with increased risk of breast cancer. A meta-analysis of more than 40 studies published in the June 2006 issue of The researchers analyzed digital mammograms of 972 women, including 318 women from London and 654 women from outside the capital. All the women had received mammography at The Princess Grace Hospital in London. The researchers found that women aged 45–54 who lived in central London were twice as likely to have very dense breasts as women who lived in outlying suburban and rural areas. Age-specific analyses indicated that breast density differences by area were more pronounced in women under age 50.Study leader Nicholas M. Perry, director of the London Breast Institute at The Princess Grace Hospital, was not particularly surprised by the study’s findings. While working as a radiologist over a 15-year period, Perry had observed that London women tended to have denser breasts than women living in outlying areas. These personal observations were the main impetus for the study. “Our study was not designed to do anything other than report on the original observation that urban women seemed to have denser breasts,” he says. “Since releasing our findings, I have received numerous comments from radiologists who have observed the same phenomenon.”The biological basis for the new finding remains to be determined. “It may simply be that London women are thinner than women living outside the capital, or it may be due to other factors,” says coauthor Stephen Duffy, an epidemiologist at Cancer Research UK and Queen Mary, University of London. “We need to carry out research on density and other breast cancer risk factors at the individual level by area of residence to get to the bottom of this.”Although mammographic density is a strong risk factor for breast cancer, it is not the only one. As an observational study, the London study did not control for factors such as suboptimal body weight, which also can influence density and is an independent risk factor for breast cancer.“Before it can be concluded that urban or rural residence influences mammographic density, it must be shown that the individuals living in urban or rural environments do not differ in one or more factors that influence density,” says Norman Boyd, a senior scientist at the Campbell Family Institute for Breast Cancer Research at Princess Margaret Hospital in Toronto. “Body weight is a strong influence on density, and it is known that obesity is more common in rural than in urban settings, and that obesity is less common among professionals than in those with other occupations. Both of these factors could explain the observed findings. If those in rural settings also had more children, that could also contribute.” Boyd’s research team is presently focused on identifying the genetic and environmental factors that influence mammographic density and the relationship of these factors to breast cancer risk.Cancer Causes & Control. Still, Perry cautions that more research is needed to determine the underlying reasons for this phenomenon, taking into account stress as well as lifestyle and environmental factors. “We intend to carry on with this research in the form of an intervention trial and hope other groups will do the same,” he says. “There is also likely to be a consensus conference before long addressing the issue of breast density and how it is modulated.”Perry’s team speculates that their observations can be at least partially attributed to environmental factors such as estrogenic particles present in traffic emissions. They present this argument in a letter to the editor published online 8 December 2007 ahead of print in In the interim, he urges urban women to be especially vigilant about breast cancer screening and to rely primarily on digital mammography, which is more effective than conventional mammography at detecting cancer in dense breast tissue. At the present time, only about 25% of centers in the United States and 10% of mammography centers in England offer digital mammography.


The appreciable excess risk of subsequent neoplasms after RT for breast cancer must be weighed against the approximately 5% reduction of breast cancer mortality at 15 years after RT.Among women with breast cancer, we compared the relative and absolute rates of subsequent cancers in 1541 women treated with radiotherapy (RT) to 4570 women not so treated (NRT), using all registered in the Swiss Vaud Cancer Registry in the period between 1978 and 1998, and followed up to December 2002. Standardised incidence ratios (SIRs) and the corresponding 95% confidence intervals (CIs) were based on age- and calendar year-specific incidence rates in the Vaud general population. There were 11 lung cancers in RT  and 17 in NRT women , 72 contralateral breast cancers in RT  and 150 in NRT women , and 90 other neoplasms in RT  and 224 in NRT women . Overall, there were 173 second neoplasms in RT women  and 391 among NRT women . The estimates were significantly heterogeneous. After 15 years, 20% of RT cases  Women treated with radiotherapy for breast cancer have an excess risk of lung, oesophageal, skin cancers and soft tissue sarcomas. Likewise, cohort studies based on cancer registries in Sweden , lung cancer (RR=1.61), oesophageal cancer (RR=2.06), leukaemias (RR=1.71), soft tissue sarcomas (RR=2.34), as well as all cancers other than breast (RR=1.20) .We therefore compared the relative and absolute risks of subsequent cancers among women treated with radiation for breast cancer (RT) to that of those not treated (NRT), using data from the Vaud Cancer Registry.n=25), the present series comprised 1549 RT and 4570 NRT breast cancer cases, registered between 1978 and 1998. These 6119 women were followed up to the end of 2002 for second primary neoplasms, emigration or death, with a total of 47 995 person-years at risk.We used the data set of the Vaud Cancer Registry, which covers incident cases of malignant neoplasms in the Canton, whose population, according to the 31 December 2000 census, was 620 294 inhabitants  and the corresponding 95% confidence intervals (CIs) was based on the Poisson distribution.As shown in vs 4.9% in NRT women; at 10 years, these figures were 11.6% vs 10.3%, and at 15 years 20.2% vs 16.3%. The difference in cumulative incidence of second neoplasms was significant (χ2(1)=4.21, P=0.04).vs 16% of NRT women had developed a second neoplasm.This study indicates that the risk of lung, breast, and also of all other neoplasms is increased in women who had received radiotherapy for breast cancer. The overall excess risk was about 30% for all neoplasms combined, comparable with those recorded by the The present findings are broadly consistent with other population-based studies. Thus, the risk of second primary cancer was evaluated in a cohort of 525 527 women with breast cancer identified from 13 population-based registries in Europe, Canada, Australia and Singapore, and followed-up between 1943 and 2000  derived from an overview of 42 000 women from 78 randomised trials (The 4% excess absolute risk in total cancer incidence 15 years after RT has to be weighed against the 5% overall reduction in breast cancer mortality at 15 years (30.5% in RT d trials . In the d trials .In the SEER data set, the risk of radiation-induced heart disease was several times higher than the risk of radiation-induced second cancer (