Breast cancer mortality has experienced important changes over the last century. Breast cancer occurs in the presence of other competing risks which can influence breast cancer incidence and mortality trends. The aim of the present work is: 1) to assess the impact of breast cancer deaths among mortality from all causes in Catalonia (Spain), by age and birth cohort and 2) to estimate the risk of death from other causes than breast cancer, one of the inputs needed to model breast cancer mortality reduction due to screening or therapeutic interventions.The multi-decrement life table methodology was used. First, all-cause mortality probabilities were obtained by age and cohort. Then mortality probability for breast cancer was subtracted from the all-cause mortality probabilities to obtain cohort life tables for causes other than breast cancer. These life tables, on one hand, provide an estimate of the risk of dying from competing risks, and on the other hand, permit to assess the impact of breast cancer deaths on all-cause mortality using the ratio of the probability of death for causes other than breast cancer by the all-cause probability of death.th century, with a peak for cohorts born in 1945–54 in the 40–49 age groups . Even though for cohorts born after 1955 there was only information for women under 50, it is also important to note that the impact of breast cancer on all-cause mortality decreased for those cohorts.There was an increasing impact of breast cancer on mortality in the first part of the 20We have quantified the effect of removing breast cancer mortality in different age groups and birth cohorts. Our results are consistent with US findings. We also have obtained an estimate of the risk of dying from competing-causes mortality, which will be used in the assessment of the effect of mammography screening on breast cancer mortality in Catalonia. Breast cancer is the leading cause of mortality among middle-aged women in many developed countries, including Catalonia, a region in the northeast of Spain, where it accounts for a fifth of all female cancer deaths and, on the average, fourteen years of potential life lost per death from this cause .th century reduced the number of women at risk for breast cancer and also competed with breast cancer as a cause of death in women with this disease. Thus, the effect of other causes of death in breast cancer incidence and mortality has changed over time depending on trends in other competing risks.Causes of death other than breast cancer may influence mortality trends in two ways: 1) by changing the number of women at risk of having breast cancer and, 2) by changing the risk of dying of breast cancer once it has developed. For example, infectious diseases at the beginning of the 20Rosenberg  used theEvaluation of the impact of mammography and adjuvant therapy on breast cancer mortality reduction can be done using statistical models, for example those found in several studies sponsored by CISNET . The modth century and 2) to assess the risk of death from other causes than breast cancer in cohorts born from 1900 to 2004. Our analysis is based on Rosenberg's work for the US and is part of a wider project that aims to model the impact of mammography in Catalonia (Spain) based on the methodology developed by Lee and Zelen for the CISNET project [The aims of the present work are: 1) to assess the impact of breast cancer mortality on overall mortality by birth cohort and age in Catalonia in the 20Catalonia is an autonomous region of Spain which has had authority over health-care planning, administration and provision since 1985. It has approximately one sixth of the Spanish population. The Catalan Health Department has implemented an independent information system and preventive programs in the region. Population breast cancer screening programs were initiated in the early nineties [By the year 2007, the Catalan Health Service was providing services to 7 million inhabitants, including 3.5 million women. The female population grew from 800.000 women in 1900 to more than 3 million in 2004. The number of breast cancer deaths increased from an average of 612 per year in the period 1975–79 to 1060 per year in the period 1990–94 and then decreased to an average of 1000 per year in the period 2000–04. For the same periods, the percentage of breast cancer deaths among overall mortality in women increased from 3.5% to 5.2% and then decreased to 3.6%.Table We grouped cohorts and ages into five-year categories in order to smooth data and minimize fluctuations present in some census and mortality data prior to 1960 , and to year of birth = calendar year of death – age at death.Deaths by calendar year were converted into deaths by year of birth (cohorts) using the relation nMx,BY, the conditional probabilities of death nqx,BY, and the proportion of expected survivors by age lx,BY [Actuarial life table methods were used to obtain the life table functions: the age specific death rate ge lx,BY . These fnMx,BY, for age groups [x, x+n) and birth cohorts BY, using the expression:1) We obtained age-specific death rates, nDx,BY is the observed number of deaths and nKx,BY the midyear population in age group x to x+n. In our analysis n is equal to 5 years.where nqx,BY in the interval [x, x+n) with the formula:2) We estimated overall probabilities of death nfx is the estimated fraction of years lived in the interval. Assuming a uniform distribution of deaths over time we have taken nfx = 0.5 for all age groups except the 0–4 age group, where nf0 = 0.4. All-cause probabilities of death are labeled as where x, x+n) as described in Step 2, using only breast cancer deaths in the numerator.3) We estimated probabilities of death from breast cancer, 4) Probabilities of death in the last age group, 85+, were estimated as nMx,BY) based on age (x) and year of birth (BY):5) We estimated the missing breast cancer mortality probabilities for earlier years of birth using an age-cohort model. The observed breast cancer death rates were used to fit the following quasi-Poisson model that provides maximum likelihood estimates of mortality rates  We subtracted the probabilities of dying from breast cancer from the overall probabilities of death to obtain the probabilities of dying from causes other than breast cancer lx,BY, which indicates the proportion of survivors at age x from birth cohort BY, using the expression:7) We obtained the life table function BY, at the beginning of each age interval, after removing breast cancer as a cause of death.Following the same nomenclature used in probabilities of death, the functions 8) We computed the ratio of Cohort multi-decrement life table functions Figure The impact of removing breast cancer as a cause of death is small under age 30 and over age 70. Below age 30 the number of breast cancer cases is small and above age 70 mortality from other causes, such as cardiovascular diseases, increases. The largest impact of removing breast cancer as a cause of death in overall mortality is observed at ages 40–54. For specific birth cohorts, the largest observed impact was in the 40–44 age group for cohorts born in 1945–49 and the 45–49 age group for cohorts born in 1950–54 . Impacts assessed using observed data for cohorts born after 1955 tended to decrease. This finding is further supported by Figure lx,BY function denotes the expected number of survivors at age x. The x, if breast cancer was eliminated as a cause of death. As an illustrative example, Table The Dif. in Table x from an initial cohort of 10,000 women, when breast cancer is removed as a cause of death. If there were no breast cancer deaths, for each 10,000 women born in 1920–24 approximately 93 would have been saved before arriving at age 70, and 118 women for the cohort born in 1930–34.The column x if breast cancer was removed as a cause of death.Figure Our study shows that breast cancer mortality in Catalonia has experienced important changes over the last century. There was an increasing impact of breast cancer on overall mortality in the first part of the century, with a peak for cohorts born in 1945–54 in the 40–49 age groups . This increasing impact could be explained by a decrease in mortality from other causes of death and increased breast cancer incidence and mortality due to changes in lifestyle and reproductive patterns . In CataThe subsequent decrease in impact was due, primarily, to the observed reduction in mortality from breast cancer during the 1990s, which affected all age groups . The only statistics that are collected in a standardized manner at the national level are mortality data. Also, this study is part of a project that aims to assessing the cost-effectiveness of different early detection strategies on the reduction of breast cancer mortality. The cost-effectiveness analysis needs information on outcomes and costs that would be difficult to obtain at the national level. On the other hand, since Catalonia has approximately one sixth of the Spanish population, we believe that some of the results of our studies will be relevant for all of Spain.This study has several limitations. First, the multi-decrement method that we used assumes independence of causes of death, which means that when breast cancer mortality is removed, the risk of dying due to the remaining causes of death is not affected. This assumption may not be true, since different causes of death may share the same risk factors. For example, body weight, smoking, and diet are associated not only with breast cancer but also with other health problems, like cardiovascular diseases. Therefore, the probability of dying of other causes could change when breast cancer death is removed. In our study, if mortality from other causes had decreased when eliminating breast cancer mortality, the impact of breast cancer mortality would be higher than the reported values. There are methods for competing risks analysis, such as cumulative incidence functions, that do not make any assumptions about independence of risks, but need information on the relationships among them ,23. ThesA second limitation concerns quality of information. The validity of population and mortality data has increased over time, but there may be errors in data from the earliest years of the study. We observed some fluctuations in the late 1930s and early 1940s, coinciding with the Spanish Civil War, a problem that could be addressed by smoothing the life table series' before using them in subsequent analyses. Also, to minimize variability we aggregated data in 5-year age groups and calendar years. The quality of mortality statistics has also changed over time, but different studies have shown that in Spain, deaths from cancer as a whole and leading cancer sites  were properly coded ,26. FurtA third limitation arises from the assumptions made when completing information on breast cancer mortality probabilities for years without available data. Data from available years seemed adequate to us to fit an age-cohort model that predicted missing information. Other approximations such as the assumption that the probabilities of dying from breast cancer at a given age would be the same in neighboring years with data, as Rosenberg did, do not change the main results (data not shown). In any case, extrapolated data for the earlier cohorts may differ from the actual values and therefore results based on these data should be interpreted with caution.th century. The multi-decrement life tables method also provided estimations of the risk of dying from competing risks that will be used in the assessment of the effect of mammography screening on breast cancer mortality.In summary, we obtained cohort life tables for causes of death other than breast cancer in Catalonia (Spain). This makes it possible to quantify the impact of removing breast cancer on overall mortality in different age groups and birth cohorts (The authors declare that they have no competing interests.MR, EV, MC, RP and JAE participated in design and coordination of the study. EV and MR performed the statistical analysis and drafted the manuscript. RG provided mortality data and contributed to the interpretation of results. MM developed the age-cohort model for breast cancer mortality. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


An epidemiological study of 1504 cases of leukoplakia seen at the Tata Memorial Hospital, Bombay, indicates that the oral cavity was the site of the disease in 95% of the cases. The buccal mucosa was the commonest site affected in all religious communities of Western India except among Parsis. Parsis, a majority of whom are non-smokers and non-chewers of tobacco, had leukoplakia more often on the anterior 2/3rd tongue than on the buccal mucosa and this pattern persisted in the distribution of cancer also, whereas people from Gujarat more often smoke; in these the buccal mucosa was commonly affected with leukoplakia, but cancer was not so frequent in this site. Statistical computation of the risk of malignant transformation indicates that males have a 4·8 times higher risk of developing cancer when they have leukoplakia than the normal population, and the females have 7 times higher risk of developing cancer in the presence of leukoplakia. It was felt that leukoplakia not associated with smoking habits had a greater chance of malignant transformation.


Case-control studies in diverse populations around the world have reported a lower risk of breast cancer in association with higher intake of dietary fibre and complex carbohydrates. Although this has not been confirmed in prospective studies in the USA, the observations have prompted the hypothesis that prolonged use of dietary fibre supplements might reduce breast cancer risk in high-incidence populations. Several possible mechanisms of action have been suggested, all involving a reduction of bioactive oestrogen levels in the blood. The various mechanisms are not necessarily mutually exclusive. First, a high-fibre diet might reduce circulating oestrogen levels by reducing the enterohepatic recirculation of oestrogen. Second, many plants and vegetables contain isoflavones and lignans capable of conversion in the bowel into weak oestrogens that may compete with oestradiol for target binding-sites. Third, a high-fibre diet is less often associated with obesity, which tends to increase availability of the biologically active 16-alpha metabolites of oestrone. Fourth, a high-fibre diet usually has a lower content of fat and a higher content of antioxidant vitamins, which may protect against breast cancer risk. Finally, diets rich in fibre and complex carbohydrates have been shown to improve insulin sensitivity, with an associated reduction in circulating oestrogen levels. Synergism between these effects offers a possible mechanism by which a high fibre intake might suppress breast cancer growth in women.


The relationship between oral contraceptives and breast cancer was evaluated among 2,022 cases and 2,183 controls participating in a multicentre breast cancer screening programme. Ever use of oral contraceptives was not related to breast cancer risk , and no overall patterns of increasing or decreasing risks were observed according to the duration of use, or time since first or most recent use. Although we had no women with extended periods of oral contraceptive use early in life, no evidence of adverse effects attributable to short-term use before age 25, before first live birth or during the perimenopausal period were observed. Further, oral contraceptives did not interact with other breast cancer risk factors, except among those with a history of two or more breast biopsies (RR = 2.0). Analyses by stage of disease revealed that risk was related to the duration of oral contraceptive use: greater than or equal to 5 years use was associated with reduced risk for in situ cancer (RR = 0.59) and increased risks for invasive cancers . These data suggest that oral contraceptive effects may vary by stage of disease, but provide no overall evidence of an association between oral contraceptives and breast cancer.


The etiology of ovarian cancer is largely unknown. One hypothesis is that the inefficient removal of the blood clots and fibrin products which are deposited in the vicinity of the ovary by retrograde menstruation might be associated with an increased risk of ovarian cancer. Several single nucleotide polymorphisms within genes which comprise the fibrinolytic system have been shown to have functional effects on the rate of blood clot degradation. These were considered to be candidate genes in the present study.We studied the genotype distributions of 12 functional SNPs of four genes  among 775 ovarian cancer cases and 889 controls.No significant associations were seen between any of the ten SNPs and the risk of ovarian cancer as a whole, or in any histologic subgroup.Germline known functional variants of genes in the fibrinolytic system are not associated with risk of ovarian cancer. Although the cause of ovarian cancer is unknown, various risk factors appear to be related to reproduction, contraception and inflammation. Parity, breast-feeding, oral contraceptives and tubal ligation are all protective. In contrast, endometriosis and talc are among the few known risk factors. On the whole, these observations suggest that factors which diminish the number of ovulatory cycles are protective and factors that increase local inflammation may be carcinogenic.Endometriosis is associated with a significantly increased risk of ovarian cancer Despite the high prevalence of retrograde menstruation in up to 90% of women The fibrinolytic system comprises a family of proteins that includes two plasminogen activators (urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA)), the zymogen plasminogen, the active form plasmin, and inhibitor proteins like plasminogen activator inhibitor type 1 (PAI1) and thrombin-activated fibrinolysis inhibitor (TAFI).The tPA is the primary mediator of local intravascular fibrinolysis. Genetic factors play a role in the variation of endothelial t-PA release uPA gene has been described. This is a substitution of C to T in the nucleotide sequence of exon 6 encoding the kringle domain resulting in Pro to Leu replacement at codon 141 (rs2227564).Elevated levels of uPA promote tumor cell spread and metastasis and are associated with relatively poor prognosis PAI1 is a serine protease inhibitor that binds to both plasminogen activators, t-PA and u-PA, forming a stable complex that is cleared from the circulation by hepatic cells In vivo animal studies demonstrate that inhibition of TAFI activity by carboxypeptidase increases thrombolysis Thrombin-activated fibrinolysis inhibitor (TAFI) is a potent inhibitor of fibrinolysis that removes carboxy terminal–lysine residues from partially-degraded fibrin and decreases plasminogen binding We propose that functional variants in these genes may be related to ovarian cancer risk. The objective of the present study was to determine if any of known functional polymorphisms of these four genes of the fibrinolytic system are associated with an increased risk of invasive ovarian cancer.Cases were ascertained through the Ontario Cancer Registry. All women newly diagnosed with invasive epithelial ovarian cancer in Ontario, Canada, from January 1995 to December 1999 were eligible. Of 1694 potentially eligible cases, 1016 women consented and provided blood samples for DNA testing. There were 775 women for whom both a DNA sample and sufficient clinical information were available and these are the subjects of the current study. Patients were categorized in four ethnic groups of Caucasian; French Canadian, East Asian and Indian .One thousand sixty-three controls were selected from healthy women who attended a screening clinic for well-women at the Women's College Hospital, Toronto, between 1996 and 2001. Of the women who were approached to participate in this study, approximately 80% agreed and provided a blood sample and completed a risk factor questionnaire. All study subjects provided informed consent for genetic testing. Controls had not been diagnosed with cancer. Study subjects were asked to provide details about their ethnic origins, including information about the place of birth of their four grandparents. 889 of these healthy women who were from the four ethnic groups of the cases were enrolled in this study.We analyzed DNA samples from 1664 subjects, 775 cases with ovarian cancer and 889 controls. Patients known to carry a BRCA1 or BRCA2 mutation were excluded. Each DNA sample was checked for a total of 12 SNPs in the four candidate genes. All these 12 variants were shown to affect the expression or function of their related gene or protein iPLEX chemistry on a MALDI-TOF MassARRAY system  was used for genotyping the 12 SNPs in eight reactions. The procedures were performed according to the manufacturer's standard protocol 2 tests (1 degree of freedom). All case-control comparisons were adjusted for age and ethnicity, using multivariate logistic regression and the adjusted P-values and odds ratios (OR) were reported. Given the number of comparisons in this study, a p-value of <0.01 was used as the criterion of statistical significance. Associations between ovarian cancer and SNP genotypes were measured in the study group as a whole and then in subgroups defined by histological type, age of diagnosis and family history. Family history was defined as one or more first- or second-degree relatives with breast cancer under age 50 or ovarian cancer.Deviations of genotype frequencies in the controls from those expected under Hardy Weinberg equilibrium (HWE) were assessed by χTwelve SNPs, representing four genes were examined in 775 ovarian cancer cases and 889 controls. Two SNPS in TAF1 (rs1087 and rs34813434) were excluded because of call rates below 90%. The call rates for the other 10 SNPs were all in excess of 95% and all were in Hardy-Weinberg equilibrium among controls. The genotypes for these ten SNPs are shown in For none of the 10 studied SNPs was the distribution of genotypes significantly different between the cases and controls . Sub-divWe hypothesized that an inherited defect in the fibrinolytic pathway could lead to an increased duration of exposure of the ovaries to blood clots containing epithelial cells originating from the Mullerian tract deposited by retrograde menses, and thereby increase the risk of ovarian cancer. This hypothesis was based on the known protective effect of tubal ligation and oral contraceptives against ovarian cancer, which prevent or reduce retrograde menstruation. In addition, previous research has demonstrated an increased activity of inhibitors of the fibrinolytic system in ovarian cancer patients. Despite the large number of samples and SNPs examined, the results of the present study were negative. The ovarian cancers that have been most strongly associated with endometriosis are the clear-cell and endometriod subtypes. Notably, in neither of these subgoups was an association found.Increased expression of several fibrinolytic modulators has been associated with increased risk for cancer development and poor prognosis Sternlicht et al We included all the SNPs of genes of the fibrinolytic system that were found to be associated with a change in either the concentration of the protein or its function.We failed to detect any significant association between fibrinolysis gene polymorphisms and the incidence of ovarian cancer in any histological subtype. If the fibrinolytic pathway is involved in ovarian cancer, the risk does not appear to be influenced by functional polymorphisms in the key genes. However, given the previous studies, which report a possible role for these enzymes in the initiation or progression of cancer, it may be that variation in the expression of the proteins in the fibrinolytic system remains relevant for ovarian carcinogenesis.


Breast cancer is the most common cancer type seen in women, accounts for 18% of all cancer types in women and the risk of a woman to get breast cancer during her life is 11%. These notified rates enable breast cancer to be defined as a preventable and if pre-diagnosed, a treatable cancer type, despite it was regarded as a terrifying type of cancer in the past.The aim of the study was to determine the lifestyle pattern of women without breast cancer in Istanbul.The study was carried out as a descriptive and cross-sectional study with 1000 women.2 and 24.5% of them preferred foods containing high fat content. The majority of the women (85.4%) did not participate in sports regularly. One third (30.3%) of the women had underwent Breast Self Examination. There was a positive family history of breast cancer for 12.1% of the women.The majority of the women (29.7%) were in the 35-44 year old age group. Out of these 93.1% gave birth before the age of 30, 29.5% breastfed for 7-12 months, 65.8% started menarche between 13-15 years of age (mean of 13.3 years), 15.5% were in menopause and had entered menopause at a mean age of 46.5 years. Their mean body mass index was 24.3kg/mSedentary lifestyles, lower Breast Self Examination and routine mammography rates and family histories of breast cancer were the risk factors that needed to be given priority for further action. Breast cancer is the most common cancer type seen in women, accounting to about 18% of all cancer types in women. Women have an 11% risk for getting breast cancer during their lifespan . AlthougIn the year 2004, it has been delineated that 371,000 new cases of breast cancer were diagnosed and it was the cause of death for 129,900 women in Europe ,6. AccorA significant proportion of determined risk factors are nonmodifiable factors, such as gender, age, race, family history, late pregnancy, early menarche and late menopause ,6. ReseaTurkish and Asian women reflect the model of a traditional family, in which a family aims at least two children who are breastfed by the mother. Nutritional habits of Turkish and Asian women show a preference for carbohydrates and fatty diet. Alcohol consumption is relatively restricted in these women due to cultural origin and religious obligations. But lately it has been observed that certain masses of women have started to adopt the western life style giving rise to considerable alcohol consumption and cigaratte smoking. In addition, the sedentary lifestyle of Turkish women has also contributed greatly to an increased risk of breast cancer .This study was conducted for the purpose of determining lifestyle behaviors, which have important roles in preventing and controlling breast cancer in women in Istanbul.The incidence of breast cancer is observed in women under the age of 25, with the risk multiplying every ten years till menopause, being particularly most common at post-menopausal period after the age of 50 . The risIt has been delineated that high education and socioeconomic level increase the risk of breast cancer by enhancing the neural communications within the brain thereby causing an increase in the level of estrogen. Furthermore, it has been highlighted that women being highly educated and maintaining a socio-economic level do have enough knowledge about the benefits of healthy nutrition, consuming which assists them in keeping good health and they start to menstruate at younger ages. Resultantly, this considerable period of time spent in getting educated, followed by exercising significant posts at work, contributes to a delay in marriage and a probable conception and childbirth at older ages, leading to an increased risk of breast cancer .Early onset of menarche (before age 12) and late menopause (after age 50) are associated with increased risk of breast cancer. According to the results of case-controlled studies, the risk of breast cancer reduces per year by 20% for each year the menarche is delayed [Having no children or the first full-term pregnancy by the age of 30 places a woman at an increased risk of breast cancer. When compared with the women whose age at first live birth is 18 or 19, the risk increases 4-5 times for the women being 30 years old at first live birth with this rate being the same for the women who have not given birth. Accordingly, however, it is controversial. Researchers show that hormone replacement therapy for longer than 5 years may increase the risk by 50%-80% at the post-menopausal period ,14, 15.et al. [Studies indicate a close relationship between the duration of breast feeding and the decrease of the risk of breast cancer ,16. For et al.  analyzedSeven prospective cohort type reproductive studies (337.819 women and 4385 invasive breast cancer cases) have notified that there is an increase of relative risk of breast cancer related to diets and other risk factors by 1.02% for pre-menopausal women and by 1.07% for post-menopausal women [et al. [et al. [There are numerous studies that are pointing to the role of regular physical activity on the possibility of decreasing the risk of breast cancer ,6,17–19.et al.  noted th [et al.  on women [et al. ,9,12.Recent studies show that breast cancer is caused by mutations and changes in the genes BRCA I and BRCA 2, and approximately 5-10% of breast cancer cases are hereditary ,11. The Recent studies have highlighted the fact that women are becoming more aware about the causes, risk factors, and early diagnosis and treatment of breast cancer, which has also shown to be a positive inclination even in Turkey where a decline in mortality rates has been observed .This study was conducted as a descriptive and cross-sectional study.This study was conducted in Istanbul with a total of 1000 women who were willing to participate. Data revealed the existence of approximately 3,000,000 women over 18 years of age in Istanbul and breast cancer was seen 24.1% in Turkey during the period 2005 and 2006. It was used following the calculation formula:n=P.Q.Zα2d2        Inclusion criteria in this study included women who did not have breast or any other gynecological from of cancer, were able to speak Turkish and were over 18 years of age.Exclusion criteria for the study included women diagnosed with breast and any other gynecological from of cancer, women who were unable to speak Turkish or were health professionals. Eleven survey forms were incompletely filled out by participants therefore they were not included in the study.Alcohol Consumption: Respondents reported their alcohol consumption status as yes or no. Quantity of alcohol consumed per month was grouped into four categories: 1-4 glasses, 5-8 glasses, 9-12 glasses and ≥13 glasses.Cigarette Smoking: Participants reported their current cigarette smoking status as yes or no. Quantity of cigarette smoking per day was grouped into five categories: 1-4 cigarettes, 5-9 cigarettes, 10-14 cigarettes, 15-19 cigarettes and ≥ 20 cigarettes.Nutritional Habits: The questions included the women's consumption of fresh fruits and vegetables and the consumption of fatty food.Physical Activity: The participants reported their sports activity and walking status and duration of these activities per day.Routine Mammography and Breast Self Examination: The questions were directed at determining health related behaviors whether the subjects had ever had a routine mammography and Breast Self Examination. In case they had, they reported the time of Breast Self Examination.Researches were instructed to maintain records of the patricipants’s including age, age at menarche, education level, marital status, employment status and type of occupation, pregnancy and menopausal status and the use of hormonal replacement therapy.A survey form with questions about the risk factors of breast cancer was filled in by 20 women in a pilot test, followed by essential revisions in the form, as a result of which the final survey form included 50-questions.Study data were collected in collaboration with a clinic practice by research staff. Researhers were assigned to collect information about healthy women through conducting interviews of women who visited the university hospital in Istanbul. Researchers filled out the survey form for the illiterate women after receiving their permission.Data were loaded in the Microsoft Excel software program and evaluated for number and percentages. Chi square tests were conducted to evaluate the relationships between cigarette smoking, alcohol consumption, exercise and nutritional status with age, educational status, marital status and employment status. The confidence interval of 95% was accepted.All of the hospital directors of nursing, staff nurses and ethics board were informed about the study and their permission was received. The women were informed about the objective of the study and the contents of the survey form and were told that their identity would be kept confidential. These subjects were then asked to give their informed consent.1).All of the 1000 women in the study were 18 years or older, with 29.7% being in the age group of 35 and 44 years, 33.4% being university graduates, 66.2% were married and 62.6% were employed (Table 2).The majority (65.8%) of the women started menarche between 13 and 15 years of age, 62.7% had given birth, 93.1% gave birth to their first child before the age of 30 (mean 22.5±4.4) and they breastfed for 7 and 12 months (29.5%). It was noted that 81.5% of the women continued to menstruate, 66.5% of the women who had stopped menstruating had entered menopause under the age of 50 (mean of 46.5±5.7 years), and 19.0% were taking hormone replacement therapy after menopause (Table 3).About 87.9% of the women had never used alcohol and 73.6% of the alcohol consumers drank 1-4 glasses of alcoholic beverages per month. One third of the women (32.9%) smoked cigarettes and about half of them used a pack or more of cigarettes per day (Table 3).On examining the women's nutritional habits, it was determined that all of 61.9% women  ate three meals a day; 84.3% consumed fresh fruits and vegetables, 75.5% low fat products and 77.4% milk and dairy products with meals (Table 3).The mean body weight of the women was 63.42 kg and their mean height was 161.64 cm. These results indicated that their mean body mass index was 24.3 . Although only 14.6% of the women reported that they regularly participated in sports activities, 53.4% stated that they walked regularly. Those regularly participating in sports and walking were spending an average of one to two hours a day for those activities . The significant differences were found in the comparison of cigarette smoking status with other variables. The rate of cigarette smoking was higher in the women between 35 and 44 years than in the other age groups.It was observed that women under the age of 25, though being educated, had an inclination to consume more alcohol. In addition, alcohol consumption was also shown to be higher for employed and single women. There was a statistically, significantly higher percentage of cigarette smoking among women being highly educated and were employed , employed  and married .Menopausal women had a lower exercise level than the premenopausal women and the difference was found to be statistically significant. The number of women getting regular exercise was higher at a statistically significant level in the women who were university graduates .Consumption of a high fat diet was the highest in employed women and among the age interval of 25-34 years. The higher percentage of the university graduates and married women who ate high fat diets was found to be statistically significant (X4).The majority of the women in this study (79.7%) did not undergo Breast Self Examination (BSE). Of those who did undergo BSE, 32.5% underwent the procedure a week after the end of menstruation. The majority of the women (97.8%) had not had a mammography test and 84.4% did not get a regular health check-up (Table 1).The frequency of women getting screening methods decreased at a statistically significant level with increasing age, particularly in the post-menopausal period  had a member of their family presenting with breast cancer.Many studies have associated the risk of breast cancer to factors such as cigarette smoking and the use of alcohol, nutritional habits, obesity, level of physical activity, menstrual and reproductive characteristics, individual’s level of stress and state of depression, besides sociodemographic characteristics. It has been emphasized that these lifestyle factors may increase the risk of development of breast cancer, or, on the contrary, they may decrease the risk. In this study, based on statements given by women in Istanbul, their lifestyle related behaviors were determined, which can be used to recommend various programs and have an important role in the prevention and control of breast cancer.The incidence of breast cancer is low in women under the age of 25. It however increases every ten years until menopause and increases significantly in the post-menopausal period after the age of 50 .It has been suggested that a high level of education and socioeconomic status may increase the risk of breast cancer. It has been suggested that starting to menstruate at a younger age (before the age of 12), entering menopause before the age of 50 and giving birth to their children at older ages (after the age of 30) increases the risk of breast cancer –11,12,23Breastfeeding is an effective factor in the prevention of breast cancer for women who give birth; it decreases the incidence of breast cancer by 25-35% . StudiesIn this study, the mean age of the women was 36.6 years, with 66.2% being married, 33.4% were university graduates, 62.6% were employed, and the longest place of residence for 53.8% was the city. Menarche manifested between the age of 13 and 15 for 65.8% of the women, 62.7% had given birth and 93.1% of the women who had given birth did so before their 30s (mean age of 22.5); 29.5% breastfed their children for 7-12 months and 26.8% for 13 months and longer, 81.5% of all women were still menstruating, 66.5% of those who were not menstruating any longer had entered menopause before their 50s (mean age of 46.5 years) and 81% of these were not taking hormone replacement therapy after menopause. Our findings indicated that the women living in Istanbul showed behaviors supporting the results of former studies and were not at increased risk from factors related to age, menarche, menopause and age of giving first birth, or the length of breast feeding.et al. [et al. [There was higher alcohol consumption among young , single, working women being highly educated and most of them were consuming 1-4 glasses of alcohol per month. Similarly, the rate of cigarette smoking was found to be higher at a statistically significant level among young and working women being highly educated (a packet or more per day). There is evidence showing that alcohol increases the risk of breast cancer, particularly if used together with cigarettes. There are many studies which report that the age when women start to drink alcohol or smoke  and the quantity of consumption  have a fundamental role in an increased risk of breast cancer ,17,24,25et al.  reported [et al.  and Hunt [et al.  reportedIn our study, most of the women had low-fat diets and consumed fresh fruits and vegetables. In particular, the women between 25-34 years who were university graduates and were married stated that they consumed high fat foods. The mean body mass index of the women in our study was within normal limits. An increase of consumption of fast-food was observed in parallel with high level of education, high socio-economic level and a fast-paced work life.et al. [High fatty diets together with alcohol, inadequate consumption of fruits and vegetables, nutritional habits containing low roughage and rich in carbohydrates lead to obesity; consequently, they increase the risk of breast cancer by raising the level of insulin and estrogen in the bloodstream ,26,29,30et al.  also repet al. [The results of this study showed that 85.4% of the women living in Istanbul do not participate in sports regularly and 46.6% do not walk regularly. The women with inadequate physical activity were mostly unemployed women with a low level of education and were in their post-menopausal period. Risendal et al.  also repet al. –21,33.Researchers are in agreement that intensity and duration of physical activity are also effective in decreasing the risk of breast cancer. They emphasize that the risk of breast cancer may decrease for a quite active woman by 10-70% and the risk may lower by 30-40% more for a woman who regularly exercises for 3-4 hours per week ,8,9,12.et al. [One of the risk factors, which women define as the most frightening one, which has an effect on the development of breast cancer is the existence of breast cancer within the family. Recent studies indicate that 5-10% of breast cancer is hereditary and that the cancer is caused by alterations and mutations in the genes, BRCA I and II ,11,12. Wet al.  noted thet al. . In the et al.  in whichThe women in Istanbul have a tendency to perform healthy behaviors, which aim to decrease or prevent the risk factors presented in the results of the epidemiological study. However, the percentages of those with inadequate physical activity  and the percentages of women with a family history of breast cancer were high.The importance of the role of the multidisciplinary approach is undeniable for the prevention and early detection in women at risk for breast cancer  Nurses, We may conclude that nurses need to emphasize on the sedentary life style, education for BSE and mammography, and give utmost consideration to positive family history in early detection programs and in public awareness programs to prevent breast cancer.On examining the demographic data, it was observed that the study sample included women being 40 years old, therefore, it was essential that data should be generalized for such a study. Researhers should also assess housewives and not restrict the age group to 40 years and under, but those over the age of 40 should also be evaluated in the future research.


There is a considerable interest in the possible relationship between psychosocial factors and the onset of breast cancer. This cohort study was based upon two nationwide and population-based central registers: The Danish Psychiatric Central Register, which contains all cases of psychiatric admissions, and The Danish Cancer Registry, which contains all cases of cancer. The register-linkage was accomplished by using a personal identification number. The study population comprised all women admitted to psychiatric departments or psychiatric hospitals in Denmark between 1969 and 1993 with an affective or a neurotic disorder. Overall, 66 648 women comprising 199 910 admissions and 775 522 person-years were included. The incidence of breast cancer in the cohort was compared with the national breast cancer incidence rates adjusted for age and calendar time. In all, 1270 women with affective or neurotic disorders developed breast cancer subsequent to the first admission as compared with the 1242 women expected, standardized incidence ratio (SIR) = 1.02 . None of the hypothetical risk factors: type of diagnosis, age or calendar period at cohort entry, age at breast cancer, alcohol abuse, alcohol/drug abuse without further specification, total number of admissions, total length of admissions, or time from first admission showed a statistically significant effect on the relative risk of breast cancer. We found no support for the hypothesis that women admitted to a psychiatric department with an affective or a neurotic disorder subsequently have an increased risk of breast cancer. © 1999 Cancer Research Campaign


Breast cancer has been increased in developing countries, but there are limited data for breast cancer risk factors in these countries. To clarify the risk for breast cancer among the Turkish women, an university hospital based nested case-control study was conducted.Between January 2000 and December 2006, a survey was prospectively conducted among women admitted to clinics of Istanbul Medical Faculty for examination and/or treatment by using a questionnaire. Therefore, characteristics of patients diagnosed with breast cancer (n = 1492) were compared with control cases (n = 2167) admitted to hospital for non-neoplastic, non-hormone related diseases.Breast cancer risk was found to be increased in women with age (≥ 50) [95% confidence interval (CI) 2.42–3.18], induced abortion (95% CI 1.13–1.53), age at first birth (≥ 35) (95% CI 1.62–5.77), body mass index (BMI ≥ 25) (95% CI 1.27–1.68), and a positive family history (95% CI 1.11–1.92). However, decreased breast cancer risk was associated with the duration of education (≥ 13 years) (95% CI 0.62–0.81), presence of spontaneous abortion (95% CI 0.60–0.85), smoking (95% CI 0.61–0.85), breast feeding (95% CI 0.11–0.27), nulliparity (95% CI 0.92–0.98), hormone replacement therapy (HRT) (95% CI 0.26–0.47), and oral contraceptive use (95% CI 0.50–0.69). On multivariable logistic regression analysis, age (≥ 50) years , induced abortion , and oral contraceptive use  were found to be associated with breast cancer risk as statistically significant independent factors.These findings suggest that age and induced abortion were found to be significantly associated with increased breast cancer risk whereas oral contraceptive use was observed to be associated with decreased breast cancer risk among Turkish women in Istanbul. Breast cancer is the most common site-specific cancer, and is the leading cause of death from cancer in women ,2. BreasBreast cancer incidence has increased in Turkey, and the estimated number of breast cancer cases was 44,253 in 2007 ,7. The dNumerous epidemiological studies on risk factors of breast cancer have produced evidence on international variations. Many studies in the literature have reported that breast cancer is related to the reproductive life of women; such as early menarche, late menopause, nulliparity, late age at first birth, diet, physical exercise and hormone usage -11. Thes2 (m2). The chi-square test was used in the statistical analyses to evaluate the significant factors associated with breast cancer risk by estimating the odds ratio (OR) and 95% confidence intervals (CI). Logistic regression was used to construct a multivariable model of independent factors associated with breast cancer risk. Forward stepwise regression was used for factor selection and, only factors with a frequency >10% that exhibited univariate significance levels of less than 0.05 were examined. For each factor in the model, the likelihood of breast cancer risk was estimated by the odds ratios and 95% CI. A p value of < 0.05 was considered significant in the statistical analyses.Between January 2000 and December 2006, we conducted a large university hospital based-nested case control study among Turkish women with or without breast cancer. A survey was prospectively conducted among women in clinics of Istanbul Medical Faculty by using a questionnaire. The Istanbul University Medical Faculty hospital is one of the busiest hospitals located in Istanbul, and over 80% of the outpatients reside in Istanbul which is the biggest city in Turkey with a population of 15 million. People who live in Istanbul have migrated from all around the Turkey. Istanbul University Medical Faculty Hospital accepts new outpatients with or without doctor's referral. Therefore, one may think that the outpatient population does reflect a general outpatient population in any hospital in Turkey. The control group consisted of 2167 women, between 18 to 70 years of age, without any known chronic illnesses , any neoplastic and hormone related diseases, selected from the waiting area of different clinics by convenience sampling. Cases with breast cancer were either selected from patients visiting our Breast Clinic for follow-up, or from our breast cancer database with age between 18 to 70 years (n = 1492). Sampling was not performed for both case and control group. An institutional ethical committee approval was obtained before starting with the study. All interviews were conducted at the hospital. Data were collected by a face to face interview using a questionnaire form after having the informed consents signed by the participants. The questionnaire consisted of 25 questions related to general characteristics of women , smoking (current smokers), alcohol intake), menstrual and reproductive history  and family history of breast cancer. The data was stored by using Microsoft Access program and the statistical analyses were performed by SPSS 15.0 program . The body mass index was calculated as weight (kg)/heightThe distribution of patients with breast cancer n = 1492) and control cases (n = 2167) according to sociodemographic characteristics , smoking , alcohol intake and family history of breast cancer) was shown in Table 492 and c2) , or first-degree family history of breast cancer  were more likely to have increased breast cancer risk (Table Patients with age (≥ 50 years)  or induced abortion , or age over 35 at first birth , or BMI  years , induced abortion , and oral contraceptive use  were found to be associated with breast cancer risk as statistically significant independent factors , and information bias . One form of hospital admission bias, the problem is that hospitalized individuals are more likely to suffer from many illnesses or symptoms. Thus they are probably not representative of the target population. On the other hand, Istanbul University Istanbul Medical Faculty Hospital is one of the busiest hospitals located in Istanbul and over 80% of the outpatients reside in the Istanbul area, which has a population of 15 million. This hospital accepts new outpatients with or without doctor's referral. Therefore, one may think that the outpatient population may potentially reflect a general outpatient population in this hospital in Turkey, and the control group consisted of women with non-neoplastic and non-hormone related illnesses selected from the waiting area of different clinics. Although the study was not population-based, patients diagnosed and treated in a large Istanbul Medical Faculty Hospital were included that limited any potential biases related with the treatment. Furthermore, strength of this study is its relatively large size, which provided reasonably stable risk estimates.The incidence of breast cancer increases with age, doubling about every 10 years until the menopause. McPherson et al reported that, of every 1000 women aged 50, two will recently have had breast cancer diagnosed and about 15 will have had a diagnosis made before the age of 50, giving a prevalence of breast cancer of nearly 2% . Vogel eOur study revealed that spontaneous abortion was associated with the decreased risk of breast cancer in univariate analysis whereas induced abortion was associated with increased breast cancer risk in both univariate and multivariable analyses. Some previous studies suggested that, induced or spontaneous abortions were associated with either increased or decreased risk of breast cancer, or no associations could be found with breast cancer risk for these factors -17. PaolIt was found that hormone replacement therapy (HRT) and oral contraceptive use were directly related to breast cancer risk in many epidemiologic studies -25. ConvTavani et al suggested  that oldThe most well established and documented data about endocrinological factors that decrease breast cancer risk are ever having breast fed and longer durations of breast feeding ,29-31. SMany studies suggest that the educational level is associated with increased risk of breast cancer -36. TavaThe results of epidemiological studies of the association between cigarette smoking and breast cancer risk have been inconsistent -39. SeveOne of the strongest risk factors for developing breast cancer is a family history of disease. In concordance with previous studies ,45, we aOur findings suggest that age and induced abortion were found to be significantly associated with increased breast cancer risk whereas oral contraceptive use was observed to be associated with decreased breast cancer risk among Turkish women in Istanbul in multivariable analysis. The discrepancies between our findings and other studies in the literature might be due to the different characteristics of Turkish women that merit further investigation.The authors declare that they have no competing interests.VO carried out study conception and design, drafting of the manuscript. BO helped to draft the manuscript and acquisition of data, analysis and interpretation of data, she has been involved in drafting the manuscript or revising critically for important intellectual content. HK helped to acquisition of data, helped in design of the study. NC participated drafting of the manuscript, editing of final version. RD performed the statistical analysis. TO helped to acquisition of data. AI, MM and MK helped to draft manuscript. AS helped to draft and critical revision of the manuscript. All authors read and approved the manuscript.


We analysed data from a case-control investigation conducted in Milan, Northern Italy, to evaluate the relation between the use of combination oral contraceptives and the risk of cancers of the breast, ovary, endometrium and cervix uteri. For the present analysis, 776 cases of histologically confirmed breast cancer, 406 of epithelial ovarian cancer and 170 of endometrial cancer aged under 60 were compared with a group of 1,282 subjects below age 60 admitted for a spectrum of acute conditions apparently unrelated to oral contraceptive use or to any of the known or potential risk factors for the diseases under study. Likewise, 225 cases of invasive cervical cancer were compared with 225 age-matched inpatient controls, and 202 cases of cervical intra-epithelial neoplasia with 202 outpatient controls identified in the same screening clinics. The age-adjusted relative risk estimates for ever vs. never use of combination oral contraceptives were 1.04  0.73-1.37) for breast cancer, 0.68 (95% CI = 0.48-0.97) for epithelial ovarian cancer, 0.50 (95% CI = 0.23-1.12) for endometrial cancer, 1.49 (95% CI = 0.88-2.55) for cervical cancer and 0.77 (95% CI = 0.50-1.18) for cervical intra-epithelial neoplasia. The risk of ovarian cancer decreased and that of invasive cervical cancer increased with longer duration of use. Neither duration of oral contraceptive use nor time since first or last use significantly altered a user's risk of other neoplasms considered. Likewise, analysis of sub-groups of age, parity or other potentially important covariates did not show any important interaction, and allowance for them by means of logistic regression did not materially modify any of the results. These data confirm that combination oral contraceptives confer some protection against ovarian and endometrial cancers but may increase the risk of invasive cervical cancer if used for several years, and indicate that the past or current pattern of oral contraceptive use in Italy is unlikely materially to affect the risk of breast cancer.


Breast cancer is the most common form of malignancy affecting women worldwide. It is also the leading cancer in females in Cyprus, with approximately 400 new cases diagnosed annually. It is well recognized that genetic variation as well as environmental factors modulate breast cancer risk. The main aim of this study was to assess the strength of associations between recognized risk factors and breast cancer among Cypriot women. This is the first epidemiological investigation on risk factors of breast cancer among the Cypriot female population.We carried out a case-control study, involving 1,109 breast cancer patients and a group of 1,177 controls who were recruited while participating in the National screening programme for breast cancer. Information on demographic characteristics and potential risk factors were collected from both groups during a standardized interview. Logistic regression analysis was used to assess the strength of the association between each risk factor and breast cancer risk, before and after adjusting for the possible confounding effect of other factors.In multivariable models, family history of breast cancer  was the strongest predictor of breast cancer risk in the Cypriot population. Late menarche  and breastfeeding  exhibited a strong protective effect. In the case of breastfeeding, the observed effect appeared stronger than the effect of pregnancy alone. Surprisingly, we also observed an inverse association between hormone replacement therapy (HRT) although this may be a product of the retrospective nature of this study.Overall the findings of our study corroborate with the results of previous investigations on descriptive epidemiology of risk factors for breast cancer. This investigation provides important background information for designing detailed studies that aim to improve our understanding of the epidemiology of breast cancer in the Cypriot population, including the study of gene-environment interactions. Furthermore, our study provides the first scientific evidence for formulating targeted campaigns for prevention and early diagnosis of breast cancer in Cyprus. BRCA genes in the mid 1990's [Breast cancer is the most frequent malignancy in the female population of Europe and North America where an estimated 1 in 9 women are at risk of developing the disease -4. In add 1990's ,9 emphasd 1990's .Cyprus is the third largest island in the Mediterranean Sea with a Greek-Cypriot population of 749,200 as recorded in July 2004, by the statistical service of the Republic of Cyprus. Data from the National Cancer Registry established in 1998 by the Ministry of Health show an average incidence of 400 female breast cancer cases per year . This coIndeed, there are no data as yet available about breast cancer risk factors in the Cypriot female population. The main aims of this report are (a) to describe the background levels of established and recognized breast cancer risk factors among Cypriot women and (b) to assess the strength of their association with breast cancer risk. In order to achieve this we carried out a case-control study, involving a breast cancer patient group and a control group of healthy Cypriot women attending mammography clinics as part of the National screening programme. A number of risk factors that modulate breast cancer such as socioeconomic status, reproductive events, family history and lifestyle factors were investigated.BRCA1 and BRCA2 genes [Interestingly, previous published work by our group has shown that the Cypriot population exhibits some unique genetic features as revealed by the identification of novel mutations in the A2 genes ,13. MoreThe sample size was determined using power calculations in order to ensure at least 90% power to detect a magnitude of association at the odds ratio scale of 1.5 at 5% statistical significance for an exposure that occurs among 10% of the controls. The cases consisted of 1109 women, between 40-70 years of age who had a histologically confirmed diagnosis of primary breast cancer between January 1999 and December of 2005. Younger cases were excluded since in addition to the fact that early-onset breast cancer may share a different aetiology, the source of the controls (i.e. mammography screening users) only effectively covers women in this age range. During the study period (January 2004 - December 2006), breast cancer cases that fulfilled the above criteria were approached while waiting for their oncologist appointment and were given an introductory letter outlining the goals of the study. Those who agreed to participate in the study subsequently underwent a personal interview with a trained interviewer. The majority of cases were ascertained from the Bank of Cyprus Oncology Centre, which operates as a referral centre and offers treatment and follow-up for up to 90% of all breast cancer cases diagnosed in Cyprus. The rest of the patients, were recruited at the Oncology Departments of the Nicosia, Limassol, Larnaca and Paphos district hospitals.The control group consisted of 1177 Cypriot women from the general population, who were invited to participate in the National programme for breast cancer screening with the use of mammography and received a negative result. Volunteers were enrolled in the study during the same calendar period as the cases, from the 5-district mammography screening centers that operate in Cyprus. Due to the narrow age span of women invited for screening (ages 50-69) younger and older women were underrepresented. Nevertheless, between the ages of 50-65, the observed age distribution roughly matched the age structure of the island's female population. Women were approached while waiting for their mammography appointment and were given an introductory letter outlining the goals of the study. Those who agreed to participate in the study subsequently underwent a personal interview with a well trained interviewer.Demographic and risk factor data were collected from both cases and controls with the use of a specially designed questionnaire, through a standardized interview. The questionnaire used in the present study was primarily based on a similar questionnaire used in the East Anglia breast cancer study . The stu2 test. The strength of association between each factor and breast cancer risk was estimated by odds ratios (ORs), calculated using logistic regression before and after adjusting for the confounding effect of all other risk factors, in multivariable models. In the case of ordered categorical variables (e.g. age at menarche), p-value for linear trend was reported. Due to the narrow age span of women invited for screening (ages between 50 and 69), women younger than 45 or older than 65 were under-represented in the study. To control for age differences between cases and controls, all model estimates (including associations with single risk factors) were therefore adjusted for age. Furthermore, the effect of restricting the investigation to women between 45-64 years of age was also tested in sensitivity analyses. In all cases, the fit of the models was assessed on the basis of the Pearson χ2 and/or Hosmer-Lemeshow goodness-of fit statistics (which compare the observed against the expected counts as estimated by the model) producing a non-significant result.We computed frequencies of categorical variables (or means and standard errors in the case of continuous variables such as age) separately for cases and controls. The frequencies were cross-tabulated and differences in participant characteristics between cases and controls were statistically assessed using the χ2 test of heterogeneity of estimates. All data manipulation and statistical analyses were performed in STATA SE 9.0.A number of characteristics investigated here are (a) dependent on each other such as pregnancy and breastfeeding, or (b) are nested in each other such as breastfeeding status vs. breastfeeding duration or (c) are expected to display a high degree of collinearity i.e. number of children and breastfeeding. The inter-relationships between these variables and the extent to which they are independently associated with breast cancer risk was firstly assessed in separate analyses (using stratification techniques or multivariable logistic models as appropriate), with the aim of identifying appropriate course of action e.g. include the variable with the strongest effect in order to avoid multicollinearity in the final model. For instance, the possible protective effect of pregnancy and the added effect of breastfeeding over the effect of pregnancy was investigated in a logistic regression model that included the main effect of pregnancy and an interaction term between pregnancy and breastfeeding (to capture the combined effect of the two variables) but no separate main effect for breastfeeding (since only women who have had a child breastfed). Similarly, as women with more children may be more likely to breastfeed (and in fact breastfeed for longer), we assessed the extent to which breastfeeding confounds or modifies any observed association between breast cancer risk and number of children by calculating Mantel-Haenszel odds ratios after stratifying by breastfeeding status along with a χA total of 2286 women - 1109 breast cancer cases and 1177 healthy controls (98% and 98% participation rate respectively) - from all five districts of Cyprus participated in the study. The mean ± SD age of cases and controls were 56.1 ± 9.1 and 55.7 ± 7.0 years respectively . Nevertheless, differences in the age distribution of cases and controls recruited into the study were observed mainly due to the under-representation of younger and older age-groups amongst the controls. Table Some strong associations were observed between the reproductive factors investigated and breast cancer risk. In general, cases were less likely than controls to have been pregnant  or to have breastfed . These variables are expected to exhibit a high degree of collinearity. Table A strong inverse association was observed between breast cancer risk and number of children. Compared to nulliparous women, crude odds ratios were 0.90, 0.84 and 0.68 in women with one, two and three children respectively; p-value for trend < 0.01. However, as expected, there was a strong association between number of children and likelihood of breastfeeding. Nearly half of women with one child reported not having breastfed at all while only 10% of them breastfed for longer than 6 months. In contrast, amongst women with 3 or more children, only 15% did not breastfeed while as many as 38% reported breastfeeding for at least one year. The Kendall's tau-b was 0.42, p-value for independence < 0.001, indicating a relatively strong and statistically significant correlation between breastfeeding duration and number of children. Considering every possible pair among the participants, this non-parametric measure is calculated on the basis of the number of occasions where the ranking of both breastfeeding duration and number of children are in the expected direction (i.e. a higher rank in one variable is accompanied by a higher rank in the other) as compared to the number of discordant pairs. The strong univariable association observed with number of children attenuated once breastfeeding was controlled for in the multivariable logistic analysis while not much change was observed in the case of breastfeeding. This cannot be simply a result of collinearity as the confidence intervals also remained largely unaffected, more likely indicating that the observed association with number of children was confounded by the effect of breastfeeding.In fact, this is also supported from the results of the stratified analysis where the estimate for the odds ratio for a one unit increase in the number of children was 0.92 (95%CI 0.80-1.05) among women who did not breastfeed and 0.97 (95%CI 0.82-1.15) among women who breastfed. The Mantel-Haenszel estimate controlling for breastfeeding is 0.94  and test of homogeneity of ORs = 0.61, indicating no evidence of effect modification in the relationship of breast cancer and number of children by breastfeeding status. Further adjusting for other variables revealed no association with parity while interestingly wide confidence intervals were observed. On the other hand, the effect estimate of breastfeeding  practically remained unchanged at 0.72 .Table None or only weak associations were observed between breast cancer risk and other risk factors investigated, for instance BMI, age at first pregnancy, smoking, exercise or use of oral contraceptives. Surprisingly, more controls (28.8%) than cases (15.5%) reported taking hormone replacement therapy (HRT). The inverse association persisted in the fully adjusted model, and in fact risk of breast cancer appeared to be inversely related to the duration of HRT use. Adjusting for number of children in the multivariable models, did not affect any of the estimates. Indicatively, the odds ratio for family history now becomes 1.62 , while the estimates were 0.83  and 0.67  in women who reached menarche between the ages of 12-14 and 15 or later respectively. Lastly, inferences were also unaffected when breastfeeding was expressed in terms of duration in the multivariable models (instead of the binary classification presented in the table).The aetiology of breast cancer is still poorly understood and known breast cancer risk factors explain only a small proportion of cases. Epidemiological studies conducted in different populations have identified a spectrum of well established and probable risk factors for breast cancer . These iThe main aim of this study was to assess the strength of associations between some recognized risk factors and breast cancer among Cypriot women. We should note that while the factors investigated here (other than BMI) were all self-reported, there is no reason to believe that any recall should be substantially differential, not least due to the standardised interview procedure by which information was collected from both groups of participants. A total of 1109 Cypriot women diagnosed with breast cancer between years 1999-2005 were recruited. It should be noted that the incidence of breast cancer in Cyprus is now around 400 cases per year. The cases in this study represents as many as 50% of the total number of cases diagnosed between 1999-2005. As many as 90% of all breast cancer cases in Cyprus are registered, receive treatment and are followed by the Bank of Cyprus Oncology Centre in Nicosia. This centralized point of access, ensures that the study participants, are to a large extent representative of all cases on the island, in terms of their socio-demographic characteristics. It should be noted that the recruitment of cases was based on the list of scheduled appointments during the study period and not on a random selection of all diagnosed cases.The 1177 controls were recruited amongst women who participated in the National breast cancer screening programme with the use of mammography, to a large extent the same population that would give rise to the cases. Since no matching was employed, unavoidable  differences in the age distribution between the cases and the controls (mainly due to the under-representation of younger and older age-groups amongst the mammography screening users) were dealt with by adjusting for age in multivariable analyses. The Cypriot National screening programme for breast cancer in all women aged 50-69 was officially introduced in 2006, after being pilot tested at a small-scale in 2003. Recent data from the Cyprus Ministry of Health suggest that more than half of the women invited respond to the call. Even so this does not imply that the sample of controls are representative of the general female population on the island, in terms of the background socio-economic characteristics and levels of potential risk factors for breast cancer in the general population.In terms of the basic demographic characteristics of the two groups, no major differences were detected in the levels of education or marital status. However, well established risk factors for breast cancer identified in other populations, such as family history of breast cancer, age at menarche and breastfeeding exhibited the strongest associations with breast cancer risk among Cypriot women ,5,10. UnHealthy volunteers who participate in epidemiological studies tend to have a higher educational level, compared to the rest of the population . In gene2) was associated with about 50% increase in breast cancer risk when compared with lean women (BMI 20 kg/m2). This association was not observed in premenopausal women. In contrast, in some studies it was observed that during the premenopausal years, breast cancer risk was slightly lower in obese women [Many studies have examined the association between body mass index (BMI) and breast cancer incidence. It was observed that in postmenopausal women, obesity  and breast cancer risk. Results from randomized controlled trials and from observational studies have shown that use of HRT increases breast cancer risk. Furthermore, the effect of HRT on breast cancer risk depends also on the different combinations of HRT as well as on the duration of usage -34. OverOnly a weak association was observed between lifestyle risk factors such as exercise and smoking. It should be noted though that these parameters refer to current status only, as no information for past habits, duration or intensity of smoking were available. As a result, any association is hard to interpret due to problems with directionality of effect e.g. associations with exercise may be more likely to reflect that women diagnosed with breast cancer are less likely to currently exercise, rather than a causal relationship between lack of exercise and breast cancer.The strongest associations with breast cancer risk in the Cypriot population were observed with family history of breast cancer, early menarche and breastfeeding. It is noteworthy that the protective effect of breastfeeding appeared stronger than the effect of pregnancy alone. Overall, the findings of our study corroborate with the results of previous investigations on descriptive epidemiology of risk factors for breast cancer. Nevertheless, this study presents the first report for breast cancer risk factors in Cypriot women and provides the first scientific evidence using National data, for executing more targeted campaigns of prevention and early diagnosis in the Cypriot population.The authors declare that they have no competing interests.AH participated in the conception and design of the study, in obtaining funding, as well as the collection, assembly, analysis and interpretation of data. ML participated in the conception and design of the study, the collection, assembly, analysis and interpretation of data as well as prepared the first draft of the manuscript with KK. NM offered guidance on statistical matters, performed statistical analysis and contributed towards the interpretation and presentation of the data in the manuscript. TM and RP participated in collection and assembly of data. EK, MD, PP, SM and YM provided patients and participated in data collection and interpretation. KK participated in the conception and design of the study, in obtaining funding, collection and assembly of data, analysis and interpretation of data and drafted the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/10/447/prepub


Sir,British Journal of Cancer on ‘The relation between socioeconomic and demographic factors and tumour stage in women diagnosed with breast cancer in Denmark, 1983–1999’.In the discussion, vs low educated women. Such a study would require that incidence density sampling had been used in the selection of controls, and The explanation of the contrasting results is, however, much more simple. The study by The This comparison of results from two Danish studies on socioeconomic risk factors for breast cancer really illustrates the importance of correct incidence density sampling of controls in case–control studies.


There is an ecological association between total and animal fat consumption and colorectal and breast cancer risk. Mortality data for breast and colorectal cancer for 24 European countries correlated, as expected, with the consumption of animal, but not vegetable, fat. There was an inverse correlation with fish and fish oil consumption, when expressed as a proportion of total or animal fat, and this correlation was significant for both male and female colorectal cancer and for female breast cancer, whether the intakes were in the current time period, or 10 years or 23 years before cancer mortality. These effects were only seen in countries with a high ( > 85 g caput-1 day-1) animal fat intake. This evidence suggests that fish oil consumption is associated with protection against the promotional effects of animal fat in colorectal and breast carcinogenesis.


Breast cancer is a significant public health problem worldwide and the development of tools to identify individuals at-risk for hereditary breast cancer syndromes, where specific interventions can be proposed to reduce risk, has become increasingly relevant. A previous study in Southern Brazil has shown that a family history suggestive of these syndromes may be prevalent at the primary care level. Development of a simple and sensitive instrument, easily applicable in primary care units, would be particularly helpful in underserved communities in which identification and referral of high-risk individuals is difficult.A simple 7-question instrument about family history of breast, ovarian and colorectal cancer, FHS-7, was developed to screen for individuals with an increased risk for hereditary breast cancer syndromes. FHS-7 was applied to 9218 women during routine visits to primary care units in Southern Brazil. Two consecutive samples of 885 women and 910 women who answered positively to at least one question and negatively to all questions were included, respectively. The sensitivity, specificity and positive and negative predictive values were determined.Of the 885 women reporting a positive family history, 211  had a pedigree suggestive of a hereditary breast and/or breast and colorectal cancer syndrome. Using as cut point one positive answer, the sensitivity and specificity of the instrument were 87.6% and 56.4%, respectively. Concordance between answers in two different applications was given by a intra-class correlation (ICC) of 0.84 for at least one positive answer. Temporal stability of the instrument was adequate (ICC = 0.65).A simple instrument for the identification of the most common hereditary breast cancer syndrome phenotypes, showing good specificity and temporal stability was developed and could be used as a screening tool in primary care to refer at-risk individuals for genetic evaluations. According to the World Cancer Report, cancer rates will increase by 50% from 10 million new cases estimated for the year 2000 to 15 million new cases per year in 2020. However, the report also provides evidence that efforts in the control of risk factors and public health strategies to increase surveillance and thus promote early cancer detection could prevent as many as one third of cancers diagnosed in the world . Germline mutations in the BRCA1 and BRCA2 genes are related to an increased risk for breast, ovarian and other cancers in the autosomal dominant Hereditary Breast and Ovarian Cancer (HBOC) syndrome [BRCA mutations are estimated to occur in 1 in 300 to 500 persons in the general population [TP53 , PTEN  and CHEK2  have been identified and are thought to have important, albeit lower contributions to hereditary breast cancer (HBC) [Positive family histories of BC and other tumors are associated with an increased risk for developing the disease and are recognized as indicators for the identification of high-risk, genetically predisposed individuals ,7. Overasyndrome ,10. Clinpulation . Other Ber (HBC) -17. Specer (HBC) ,11.Taking a family history has long been considered an integral part of the medical evaluation and is particularly important in genetic risk evaluation and risk management protocols, where it may ultimately help in the design of strategies to reduce cancer-associated mortality . Health In Brazil, several barriers to the identification and counseling of individuals at-risk for HBCS have been identified and include lack of well established cancer genetic counseling services, absence of specific training programs in cancer genetics, small numbers of certified clinical geneticists and their unequal geographic distribution in the country . The genIn this study, a simple instrument to inquire about the family history of BC, OC and CRC was developed to identify women at-risk for HBCS during their primary care visits. We tested the instrument's sensitivity and positive and negative predictive values to identify different HBC phenotypes and its ability to identify women with higher lifetime risks for developing BC as estimated by current risk models.Programa Saúde da Família . This program was created in the mid-90's and is based upon multidisciplinary teams, composed by a physician, nurse, one or two nurse assistants and 4–6 lay community health workers. This team provides primary health care to a geographically defined group of approximately 600 families. The Programa Saúde da Família has expanded rapidly and nowadays provides health care to about half of the population [In April of 2004, a population-based cohort study (the Núcleo Mama Porto Alegre – NMPOA Cohort) was started in 18 primary care units of the city of Porto Alegre, Southern Brazil ,27. The pulation -30.BRCA mutations [To identify individuals and families at risk for HBC syndromes within the cohort, an instrument with seven questions, named FHS-7, was developed and applied to all women that visited the participating primary care units from April 2004 to March 2006 Table . FHS-7 wutations . In addiutations . PatientOf the 9218 women enrolled in the NMPOA cohort, 1285 (13.9%) women who visited the primary care units participating in the cohort, answered positively to at least one of the seven questions about family history of cancer in FHS-7 and those above age 18 years (1246) were referred for GCRA. Of these, 902 women from 829 families were seen for GCRA during a period of three years (2005–2007), and 885 agreed to participate in the study presented here  Lifetime breast cancer risk estimates (LBCRE): were obtained using the Claus Tables and the Gail and Tyrer-Cuzick models [k models -33. Uppeb) Patients at high-risk for a hereditary breast cancer syndrome (HBC): all patients fulfilling criteria for a BC predisposition syndrome upon pedigree analysis were classified in this group. Criteria for the definition of HBC syndromes are detailed below. For the HBOC syndromes, the American Society of Clinical Oncology (ASCO) criteria were used [BRCA1 or BRCA2 mutation were determined for each patient using mutation prevalence tables and the Penn II mutation prediction model [ere used ,36. In aon model -37. All on model  were useon model  and Eeleon model  and for on model -38.Intra-class correlation (ICC) were used to verify the agreement between results obtained by the instrument and the genetic cancer risk evaluation. In addition, ICC was used to measure agreement between answers to the instrument when applied in two different occasions, for temporal stability verification.To determine the cutoff value for the original FHS-7 instrument, the ROC curve was used and the values for specificity and sensitivity were calculated. To compare the mean risk estimates obtained using the Gail, Claus and Tyrer-Cuzick models, t test for different samples was applied. In all analyses a significance level of 0.05 was considered and two-sided analyses were performed.Demographic and reproductive data of the sample studied are summarized in Table After application of FHS-7, 885 women responded affirmatively to at least one question: 375 women (42.4%) reported a first-degree family history of BC or OC, 109 (12.3%), bilateral BC, 10 (1.1%) male BC, 40 (4.5%) BC and OC double primary tumors, 557 (62.9%), BC under the age of 50 years, 222 (25.1%), ≥ 2 relatives with BC and/or OC and 222 (26.2%) ≥ 2 relatives with BC and/or CRC in their families.Table Regarding temporal stability of the instrument, ICC for each of the 7 questions were: 0.72 for BC or OC in a first-degree relative, 0.74 for BC diagnosed <50 years in a relative, 0.61 for ≥ 2 relatives with BC and/or OC, 0.38 for bilateral BC in a relative, 0.17 multiple BC and OC in a relative and 0.47 for ≥ 2 relatives with BC and/or CRC in the family. For the question about multiple BC and OC in a relative there were only 5 positive answers in GCRA. For the male BC question there was no positive answer and thus, the ICC coefficient could not be calculated. When considering the instrument as a whole, the presence of at least one positive answer in both instrument applications had an ICC of 0.65.Application of FHS-7 in primary care units to screen for HBC phenotypes resulted in the identification of 211/885 individuals  with a family history fulfilling such diagnoses, including the HBOC, HBCC and Li-Fraumeni-Like syndromes; no patient reported a family history consistent with Li-Fraumeni syndrome. In contrast, only 30/910  individuals that responded negatively to all of the 7 questions of the instrument had criteria for one or more of such phenotypes upon GCRA  tumors, the ICC was very low and this may be a consequence of the small number of positive answers obtained for these questions. An additional reason that may partially explain some of the low ICC values is that upon retrieval of confirmatory documents during GCRA, some of the cancer diagnoses were not confirmed. This occurred particularly often in the multiple primary cases, and in those, OC was usually not confirmed. Uncertainty about the cancer family history, especially when there is more than one cancer diagnosis in the family, may also be frequent at the first visit in the primary care unit and may be confirmed or refuted before the genetic evaluation. Another concern would be a potential bias of ascertainment due to non-inclusion of women who did not attend genetic cancer risk assessment sessions. In fact, the demographic data of women with a positive family history who underwent GCRA (attenders) differed significantly in some aspects from those of women who did not undergo GCRA (non-attenders). Non-attenders were generally younger, less educated, and had undergone a breast biopsy less often than attenders (p < 0.001), as demonstrated elsewhere. However, for most of the questions in the family history questionnaire, there was no significant difference between the proportion of positive answers between attenders and non-attenders .et al. (2007) [Regarding the ability of FHS-7 to identify particular HBC phenotypes, the presence of at least one positive answer was associated with good sensitivity at acceptable specificity. This was particularly the case for the identification of the HBOC phenotype, and less for the Li-Fraumeni-Like phenotype, however, the instrument was not originally developed to identify Li-Fraumeni-Like families. The worst performance was in the identification of Li-Fraumeni-Like families and all of them were defined as Li-Fraumeni-Like by Eeles criteria only . These f. (2007)  have recTP53 germline mutation.A significant proportion of women from the community-based sample studied here presented a family history of BC, OC and/or CRC and upon genetic risk evaluations: 6.2% of them had phenotypes of specific BC predisposition syndromes. These results have been reported elsewhere in detail in . Even coIn conclusion, simple family history questionnaires such as the one developed here can be used in BC risk-screening programs at the primary care level as important tools for the identification of individuals who may benefit from specific interventions.The authors declare that they have no competing interests.PAP, EIP, LK and MC developed the initial design of the genetics study within the cohort. JG, FLR, EA, SMM, EB and VBR contributed to data acquisition and handling. PAP, JG, AVS and SC were responsible for data analysis, and interpretation. All authors revised the manuscript and agreed with the final submitted version of the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/9/283/prepub