Role and impact of menstrual and reproductive factors on breast cancer risk in Japan.

The aim of this study was to clarify the role and impact of menstrual and reproductive factors in relation to breast cancer and its hormone receptor-defined subtype, overall and separately among premenopausal and postmenopausal women in a low-risk population, using data from the Japan Public Health Center-based Prospective study. A total of 55 537 women aged 40-69 years completed a self-administered questionnaire, which included items about menstrual and reproductive history. During 1990-2002, 441 newly diagnosed cases of breast cancer were identified. Early age at menarche for premenopausal women, late age at natural menopause, nulliparity and low parity for both premenopausal and postmenopausal women, and late age at first birth for postmenopausal women were significantly associated with an increased risk of breast cancer. No overall significant associations were seen between the use of exogenous female hormones or breast feeding and breast cancer risk. Age at menarche and age at natural menopause were somewhat more closely associated with the risk of progesterone receptor-negative than positive breast cancer although no difference was observed for estrogen receptor status. Risks associated with parity, number of births and age at first birth did not significantly differ by hormone receptor-defined breast cancer. Our findings suggest that menstrual and reproductive factors may play an important role in the development of breast cancer among low-risk populations, similarly as they do in Western populations, and that risk factors might differ by hormone receptor status.     

A prospective study of reproductive and menstrual factors and colon cancer risk in Japanese women: findings from the JACC study

The effects of reproductive factors on the etiology of colon cancer in Asian populations remain unexplored. So we examined 38,420 Japanese women aged 40-79 years who responded to a questionnaire on reproductive and other lifestyle factors from 1988 to 1990 in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. During an average 7.6 years of follow-up, we documented 207 incident colon cancers. Multivariate analysis indicated that colon cancer risk was likely to be lower among parous women than among nulliparous. Women who had two abortions or more had a 72% higher risk of developing colon cancer [relative risk (RR) 1.72; 95% confidence interval (CI) 1.16-2.55; trend P < 0.01] compared with women who never had an abortion. The RR of colon cancer among postmenopausal women significantly decreased with increasing age at menarche (trend P = 0.01). No apparent association between colon cancer and gravida, age at first birth, age at menopause, or duration of menstruation was seen. These prospective data support the hypothesis that female reproductive events modify colon cancer risk, and suggest that reproductive factors, particularly age at menarche and having an abortion, may be of importance in the etiology of colon cancer among Japanese women.     

Association of menstrual and reproductive factors with breast cancer risk: results from the Shanghai Breast Cancer Study

The incidence of breast cancer among women in Shanghai, a traditionally low-risk population, has increased substantially over the past 20 years. To evaluate the association of menstrual and reproductive factors with breast cancer risk and the influence of these factors on the temporal trend of breast cancer incidence, we analyzed data from the Shanghai Breast Cancer Study, a population-based case-control study of breast cancer recently completed among Chinese women in urban Shanghai. In-person interviews were completed for 1,459 women newly diagnosed with breast cancer between ages 25 and 64 and for 1,556 controls frequency-matched to cases by age. Unconditional logistic regression was employed to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) related to menstrual and reproductive factors. Earlier menarcheal age, nulliparity, and later age at first live birth were associated with increased risk of breast cancer among both pre- and post-menopausal women, while never having breast-fed and later age at menopause were associated with elevated risk only among post-menopausal women. Among controls, 32% of younger women (40 years) reported starting menarche at age of 13 or younger, and this factor contributed to 44% of cases diagnosed among younger women and 26% to 28% of cases in older women. Older age at first live birth or at menopause explained a considerable portion of cases diagnosed in older, but not younger, women. Our study suggests that the changes in menstrual and reproductive patterns among women in Shanghai have contributed to the recent increase in breast cancer incidence, particularly among younger women.     

The associations between a polygenic score, reproductive and menstrual risk factors and breast cancer risk

We evaluated whether 13 single nucleotide polymorphisms (SNPs) identified in genome-wide association studies interact with one another and with reproductive and menstrual risk factors in association with breast cancer risk. DNA samples and information on parity, breastfeeding, age at menarche, age at first birth, and age at menopause were collected through structured interviews from 1,484 breast cancer cases and 1,307 controls who participated in a population-based case–control study conducted in three US states. A polygenic score was created as the sum of risk allele copies multiplied by the corresponding log odds estimate. Logistic regression was used to test the associations between SNPs, the score, reproductive and menstrual factors, and breast cancer risk. Nonlinearity of the score was assessed by the inclusion of a quadratic term for polygenic score. Interactions between the aforementioned variables were tested by including a cross-product term in models. We confirmed associations between rs13387042 (2q35), rs4973768 (SLC4A7), rs10941679 (5p12), rs2981582 (FGFR2), rs3817198 (LSP1), rs3803662 (TOX3), and rs6504950 (STXBP4) with breast cancer. Women in the score’s highest quintile had 2.2-fold increased risk when compared to women in the lowest quintile (95 % confidence interval: 1.67–2.88). The quadratic polygenic score term was not significant in the model (p = 0.85), suggesting that the established breast cancer loci are not associated with increased risk more than the sum of risk alleles. Modifications of menstrual and reproductive risk factors associations with breast cancer risk by polygenic score were not observed. Our results suggest that the interactions between breast cancer susceptibility loci and reproductive factors are not strong contributors to breast cancer risk.     

Analysis of menstrual, reproductive, and life-style factors for breast cancer risk in Turkish women: a case-control study

The aim of this study was to investigate the association between menstrual, reproductive, and life-style factors and breast cancer in Turkish women. In a hospital-based case-control study in Ankara, 622 patients with histologically confirmed breast cancer were compared with 622 age-matched controls, admitted to the same hospital for acute and non-neoplastic diseases. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) related to risk factors. Overall, menopausal status and age at menopause were found to be significantly associated with breast cancer. Having a full-term pregnancy and early age at first birth were associated with decreased breast cancer risk (OR = 0.45, 95% CI = 0.30-0.66; OR = 0.34, 95% CI = 0.22-0.53, respectively). Postmenopausal women with lactation longer than 48 mo had reduced risk of breast cancer (OR = 0.36, 95% CI = 0.14-0.93). In conclusion, decreased parity, late age at first birth, early menopause, and shorter duration of lactation were the most important determinants of breast cancer risk in Turkish women.     

Analysis of menstrual, reproductive, and life-style factors for breast cancer risk in Turkish women

The aim of this study was to investigate the association between menstrual, reproductive, and life-style factors and breast cancer in Turkish women. In a hospital-based case-control study in Ankara, 622 patients with histologically confirmed breast cancer were compared with 622 age-matched controls, admitted to the same hospital for acute and non-neoplastic diseases. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) related to risk factors. Overall, menopausal status and age at menopause were found to be significantly associated with breast cancer. Having a full-term pregnancy and early age at first birth were associated with decreased breast cancer risk (OR=0.45, 95% CI=0.30–0.66; OR=0.34, 95% CI=0.22–0.53, respectively). Postmenopausal women with lactation longer than 48 mo had reduced risk of breast cancer (OR=0.36, 95% CI=0.14–0.93). In conclusion, decreased parity, late age at first birth, early menopause, and shorter duration of lactation were the most important determinants of breast cancer risk in Turkish women.     

Impact of reproductive factors and lactation on breast carcinoma in situ risk

Incidence rates for breast carcinoma in situ (CIS) have increased markedly over the past 20 years. Breast CIS, detected primarily on mammography, now represents 30-45% of all screened detected breast cancers. We conducted a large population-based case-control study to evaluate the impact of reproductive factors and lactation on breast CIS risk. Case subjects were newly diagnosed with breast CIS at ages 35-64 years between March 1, 1995 and May 31, 1998 (n = 567), resided in Los Angeles County and were born in the United States. Control subjects (n = 614), identified through random digit dialing, fulfilled the same eligibility criteria and were required to have had at least one screening mammogram in the 2-year period before their interview. Women with a positive family history of breast cancer had a 2-fold increase in breast CIS risk. Parous women were at reduced risk relative to nulligravid women (odds ratio [OR] = 0.67, 95% confidence interval [CI] = 0.46-1.00). Among nulliparous women, pregnancy was unrelated to breast CIS risk. Among parous women, risk declined with each additional term pregnancy (p-trend = 0.003). No associations were found with age at first term pregnancy, induced abortion or miscarriage. Long duration of breast-feeding (> or =24 months) was associated with increased risk (OR = 2.00, 95% CI = 1.11-3.60). The observed effects of family history and pregnancy on breast CIS risk are consistent with those observed for invasive breast cancer. The results for breast-feeding are contrary to what has been observed in studies of invasive breast cancer.     

FGFR2 intronic polymorphisms interact with reproductive risk factors of breast cancer: Results of a case control study in Japan

Recently, 2 genome‐wide association studies demonstrated that single nucleotide polymorphisms (SNPs) of the fibroblast growth factor receptor 2 (FGFR2) gene at intron 2 are significantly associated with the risk of female breast cancer. As the next step, it is necessary to evaluate the interaction between these SNPs and known risk factors of breast cancer because such an evaluation could elucidate mechanisms of carcinogenesis and lead to preventive advances. We conducted a case‐control study of 456 newly and histologically diagnosed breast cancer cases and 912 age‐ and menopausal status‐matched noncancer controls. The impact of 5 FGFR2 intronic SNPs on the risk of breast cancer and the interactions between these SNPs and various known risk factors of breast cancer were evaluated in both pre and postmenopausal women. We observed a statistically significant association between 4 SNPs and breast cancer risk and these 4 SNPs were in strong linkage disequilibrium in the Japanese population. rs2420946 was associated with a population‐attributable risk of 17.7%. We found that FGFR2 polymorphisms interact with family history of breast cancer (interaction p = 0.003) and reproductive risk factors, namely, age at menarche (interaction p = 0.019) and parity (interaction p = 0.026). Of note, a significant association between body mass index (BMI) ≥ 25 and FGFR2 polymorphism was observed among postmenopausal women (trend p = 0.012), but not among premenopausal women. In contrast, BMI < 25 had no significant association with this polymorphism regardless of menopausal status. These findings suggest that FGFR2 intronic SNPs affect the reproductive hormone‐related pathway and contribute to the development of female breast cancer in the Japanese population. © 2009 UICC     

Breast cancer risk following Hodgkin lymphoma radiotherapy in relation to menstrual and reproductive factors

Background:

Women treated with supradiaphragmatic radiotherapy (sRT) for Hodgkin lymphoma (HL) at young ages have a substantially increased breast cancer risk. Little is known about how menarcheal and reproductive factors modify this risk.

Methods:

We examined the effects of menarcheal age, pregnancy, and menopausal age on breast cancer risk following sRT in case–control data from questionnaires completed by 2497 women from a cohort of 5002 treated with sRT for HL at ages <36 during 1956–2003.

Results:

Two-hundred and sixty women had been diagnosed with breast cancer. Breast cancer risk was significantly increased in patients treated within 6 months of menarche (odds ratio (OR) 5.52, 95% confidence interval (CI) (1.97–15.46)), and increased significantly with proximity of sRT to menarche (P_trend<0.001). It was greatest when sRT was close to a late menarche, but based on small numbers and needing reexamination elsewhere. Risk was not significantly affected by full-term pregnancies before or after treatment. Risk was significantly reduced by early menopause (OR 0.55, 95% CI (0.35–0.85)), and increased with number of premenopausal years after treatment (P_trend=0.003).

Conclusion:

In summary, this paper shows for the first time that sRT close to menarche substantially increases breast cancer risk. Careful consideration should be given to follow-up of these women, and to measures that might reduce their future breast cancer risk.     

Lifestyle, parity, menstrual and reproductive factors and risk of gallbladder cancer.

Together with thyroid cancer, cancer of the gallbladder is the only non-sex hormone-related cancer displaying a female preponderance, with incidence being 3-4 times more common among women. We carried out this study to evaluate the role of menstrual, reproductive and lifestyle factors in gallbladder carcinogenesis. A case-control study involving 64 newly diagnosed cases of gallbladder cancer and 101 cases of cholelithiasis was carried out. A detailed menstrual and reproductive history was illustrated beside detailed lifestyle history, in particular consumption of betel nut, tobacco and alcohol and smoking, odds ratio was calculated. Mean age of the patients with cancer was 51+/-1.2 years while it was 40.9+/-1.2 years for gallstones; 69% of cancer patients and 90% of gallstones patients were females. More than half of the cancer patients (53%) and 43% of the gallstone patients were illiterate. A past history of typhoid was present in 22% of cancer patients and 13% of gallstone patients, while 35% of cancer and 25% of gallstone patients were chewers, 18.1 and 9.9% were smokers, and 10% of cancer and 2% of gallstone patients consumed alcohol. Mean age of menarche was 13.4+/-1.2 years among female patients with cancer while it was 14.0+/-1.4 years for gallstone patients. Higher age at menarche (>13 years, OR 2.48, 95% confidence interval (CI) 1.16-5.3), higher number of childbirths(>3 births, OR 3.92; 95% CI 1.4-10.3), higher number of pregnancies (>3 pregnancies, OR 6.66, 95% CI 1.8-23.4), and higher age at last childbirth (>25 years, OR 2.97, 95% CI 1.04-8.5) were found to have significantly higher risk of developing gallbladder cancer. In conclusion, tobacco chewing and smoking are associated with increased odds of gallbladder cancer. Similarly early menarche, late menopause, multiple pregnancies and childbirth increased the risk of gallbladder cancer.     

Combined effect of family history and reproductive factors on breast cancer risk

This study evaluated the combined effect of a family history of breast cancer and each of three reproductive factors on breast cancer risk in the sisters of 404 breast cancer patients. The patients had a family history of breast cancer in a sister and mother or in two sisters. Risks were highest in sisters who had menarche at an early age or who first gave birth at a late age whether the patient had unilateral or bilateral disease, and with low parity only when the patient had bilateral disease. The bilateral group may have included a higher fraction of hereditary forms of breast cancer than the unilateral group. Because similar findings have been reported previously for breast cancer patients in general, the current results suggest that these reproductive factors have an effect on breast cancer risk independent of a family history of the disease. It is important, therefore, that the combined effects of these risk factors be taken into account when counseling women about their breast cancer risks.     

Menstrual and reproductive factors and risk of breast cancer in Asian-Americans.

We conducted a population-based case-control study of breast cancer among Chinese-, Japanese- and Filipino-American women in Los Angeles County Metropolitan Statistical Area (MSA), San Francisco-Oakland MSA and Oahu, Hawaii. One objective of the study was to quantify breast cancer risks in relation to menstrual and reproductive histories in migrant and US-born Asian-Americans and to establish whether the gradient of risk in Asian-Americans can be explained by these factors. Using a common study design and questionnaire in the three study areas, we successfully conducted in-person interviews with 597 Asian-American women diagnosed with incident, primary breast cancer during the period 1983-87 (70% of those eligible) and 966 population-based controls (75% of those eligible). Controls were matched to cases on age, ethnicity and area of residence. In the present analysis, which included 492 cases and 768 controls, we observed a statistically non-significant 4% reduction in risk of breast cancer with each year delay in onset of menstruation. Independent of age at menarche risk of breast cancer was lower (odds ratio; OR=0.77) among women with menstrual cycles greater than 29 days. Parous Asian-American women showed a significantly lower risk of breast cancer then nulliparous women (OR=0.54). An increasing number of livebirths and a decreasing age at first livebirth were both associated with a lower risk of breast cancer, although the effect of number of livebirths was no longer significant after adjustment for age at first livebirth. Women with a pregnancy (spontaneous or induced abortions) but no livebirth had a statistically non-significant increased risk (OR=1.84), but there was no evidence that one type of abortion was particularly harmful. A positive history of breastfeeding was associated with non-significantly lower risk of breast cancer (OR=.78). There are several notable differences in the menstrual and reproductive factors between Asian-Americans in this study and published data on US whites. US-born Asian Americans had an average age at menarche of 12.12 years-no older than has been found in comparable studies of US whites, but 1.4 years earlier than Asian women who migrated to the US. Asian-American women, particularly those born in the US and those who migrated before age 36, also had a later age at first birth and fewer livebirths than US whites. A slightly higher proportion of Asian-American women breastfed, compared with US whites. The duration of breastfeeding was similar in US-born Asians and US whites, but was longer in Asian migrants, especially those who migrated at a later age. Menstrual and reproductive factors in Asian-American women are consistent with their breast cancer rates being at least as high as in US whites, and they are. However, the effects of these menstrual and reproductive factors were small and the ORs for migration variables changed only slightly after adjustment for these menstrual and reproductive factors. These results suggest that the lower rates of breast cancer in Asians must be largely as a result of other environmental/lifestyle factors.     

The influence of menstrual risk factors on tumor characteristics and survival in postmenopausal breast cancer

Introduction  

Hormonal factors are implicated in tumor progression and it is possible that factors influencing breast cancer induction could affect prognosis. Our study investigated the effects of menstrual risk factors on tumor characteristics and survival in postmenopausal breast cancer.     

Association between lifestyle,menstrual/reproductive history,and histological factors and risk of breast cancer in women biopsied for benign breast disease

Purpose

Women with benign breast disease (BBD) have an increased risk of subsequent breast cancer. However, whether conventional breast cancer risk factors influence risk of breast cancer among women with BBD is unclear. In this study, we investigated the associations of lifestyle, menstrual/reproductive, and histological factors with risk of breast cancer among women biopsied for BBD.

Methods

We conducted a case–control study, nested within a cohort of 15,395 women biopsied for BBD at Kaiser Permanente Northwest between 1971 and 2006. Cases were women who developed a subsequent invasive breast cancer during follow-up; controls were individually matched to cases on age at BBD diagnosis. A total of 526 case–control pairs were included in the study. We calculated crude and multivariable OR and 95% CI for the associations between lifestyle, menstrual/reproductive, and histological factors and breast cancer risk using conditional logistic regression.

Results

Compared to premenopausal women, postmenopausal women had reduced risk of subsequent breast cancer (OR 0.60; 95% CI 0.39–0.94), whereas women who ever used hormone replacement therapy (HRT) had increased risk (OR 3.61; 95% CI 1.68–7.75), as did women whose BBD lesion showed atypical hyperplasia (OR 5.56; 95% CI 2.05–15.06). Smoking, BMI, early menarche, multiparity (≥4), history of oophorectomy, and extent of lobular involution were not associated with risk of breast cancer.

Conclusion

This study suggests that use of HRT and having atypical hyperplasia are associated with increased risk of breast cancer among women with BBD, while postmenopausal women with BBD have a reduced risk.

     

Impact of familial risk factors on management and survival of early-onset breast cancer: a population-based study

This population-based study evaluates the impact of a strong family history of breast cancer on management and survival of women with early-onset disease. We identified all breast cancer patients 相似文献   

Consumption of soy foods and the risk of breast cancer: findings from the Japan Collaborative Cohort (JACC) Study

OBJECTIVE: The association between a lower incidence of breast cancer within the Asian population and the consumption of a diet high in soy has recently been the subject of much attention. To examine whether soy foods really have protective effects against breast cancer and how their influence on breast cancer is modified according to menopausal status, we conducted a population-based, prospective cohort study in Japan. METHODS: We analyzed the data from the Japan Collaborative Cohort (JACC) Study. From 1988 to 1990, 30,454 women aged 40-79 years, completed a questionnaire on diet and other lifestyle features. Hazard ratios (HRs) were computed to examine the association between soy intake and the risk of breast cancer. RESULTS: During the mean follow-up of 7.6 years, 145 cases of breast cancer were documented. We found no significant association between the risk of breast cancer and consumption of tofu, boiled beans, and miso soup; the multivariate HRs (95% CI) in the highest category of consumption were 1.14 (0.74-1.77), 0.77 (0.47-1.27) and 1.01 (0.65-1.56), respectively. Only among postmenopausal women, we found no significant associations between soy foods and the risk of breast cancer. CONCLUSIONS: This prospective study suggests that consumption of soy food has no protective effects against breast cancer. Further large-scale investigations eliciting genetic factors may clarify different roles of various soybean-ingredient foods on the risk of breast cancer.     

Ages at different reproductive events, numbers of menstrual cycles in between and breast cancer risk

One hundred and seventy-five pathologically confirmed new cases of female breast cancer in National Taiwan University Hospital were selected as the case group. Four hundred and fifty-seven inpatient controls were individually matched for each case by age and date of admission. Information of reproductive factors and potential confounders were collected from questionnaire interview and medical records. Menstrual cycles before and after first fuIl-term pregnancy were estimated from the questionnaire. Conditional logistic regression was used to estimate the effects of reproductive risk factors and numbers of menstrual cycles before and after first full-term pregnancy. After adjusting for educational level, body mass index, family history of breast cancer and oral contraceptive use, age at menarche and menopause only showed borderline significance. Age at first full-term birth predicted breast cancer risk better. Parity was the most important protective factor. Number of menstrual cycles before first full-term pregnancy was also positively associated with breast cancer risk with linear trends.     

Cumulative number of menstrual cycles and breast cancer risk: results from the E3N cohort study of French women

Objective: To examine the relationship between breast cancer risk and the cumulative number of cycles before a first full-term pregnancy (FTP) and lifetime, taking age at menarche and at onset of regular cycling, periodicity and regularity of cycles, duration of periods of pregnancy, and lactation, oral contraceptive (OC) use, and age at menopause into account. Methods: The data were taken from the E3N prospective cohort study of women aged 40–65 years in 1990. A total of 1718 breast cancer cases were identified during the 579,525 person-years of follow-up. Results: There was a highly significant linear relationship between breast cancer risk and both the cumulative number of cycles before a first FTP (p for trend < 0.0001) and lifetime (p for trend < 0.001), with multivariate relative risk (RR) of a similar magnitude for both variables. Compared to women with a lifetime number of cycles 402 ( 30 years), the RR for those with a lifetime total of 403–441, 442–480, 481–520, and 521 cycles were 0.95 (0.75–1.21), 1.21 (0.97–1.52), 1.23 (0.96–1.58), and 1.60 (1.25–2.04), respectively. Results restricted to never OC users were similar. Conclusions: Further investigation is needed to clarify whether the underlying factor is repeated exposure to fluctuating hormones, the number of anovular/ovular cycles, or the relative importance of the follicular and luteal phases.     

Trends in the incidence rate and risk factors for breast cancer in Japan

The incidence rate of breast cancer in Japanrose more than two-fold from 1959–60 to 1983–87.To assess to what extent this increase canbe explained by changes in the prevalence offour major risk factors of breast cancer (i.e.age at menarche, age at first birth, ageat menopause, and parity), we estimated the probabilityof developing breast cancer based on the jointdistribution and relative risks of these four riskfactors. The age-specific incidence rate during 1959–60 reportedby the Miyagi Prefectural Cancer Registry was usedto estimate the baseline hazard rate for womenwithout the four risk factors in the sameage group. Assuming that the baseline hazard rateis constant during all periods, we calculated theexpected incidence rates during the periods of 1959–60,1962–64, 1968–71, 1973–77, 1978–81, and 1983–87 for eachage group. Large discrepancies were noted between theobserved and expected incidence rates during 1983–87 inall age groups. The change in the jointdistribution of the four risk factors accounted forless than 40% of the increase observed from1959–60 to 1983–87, suggesting the effects of otherpowerful risk factors.     

BRCA2 mutation carriers,reproductive factors and breast cancer risk

Background

Germline mutations in the BRCA genes dramatically increase the risk of breast cancer. In the general population, breast cancer risk is affected by age at menarche, by age at first birth, by the number of births and by the duration of breast feeding. Whether this is true for mutation carriers is not clear.

Methods

In a case–control study, nested in a population-based cohort of the Icelandic Cancer Detection Clinic, two groups of cases were defined, matched on year of birth, on age at diagnosis and on age when giving information on reproductive factors: 100 carriers of the Icelandic founder BRCA2 mutation 999del5, and 361 BRCA2-negative cases. The mean age at diagnosis was 48 years. There were 1000 women in a matched group of unaffected controls. Conditional logistic regression was used for the analysis.

Results

An increased number of births was associated with a decreased risk of breast cancer in BRCA2-negative cases but not in BRCA2-positive cases. A negative association between risk and duration of breast feeding was observed only in the mutation carriers. These associations were not statistically significant, but the effects of the two variables differed significantly according to mutation status (P = 0.007 and P = 0.045 for interaction with number of births and with duration of breast feeding, respectively). This was maintained when limiting the analysis to women diagnosed older than the age of 40 years.

Conclusion

The association between breast cancer and the number of pregnancies and between breast cancer and the duration of breast feeding was not the same for carriers and noncarriers of a detrimental BRCA2 mutation. In the context of other epidemiological and laboratory studies, this may indicate that the product of the BRCA2 gene has a function relating to the differentiation of epithelial tissue in the breast.