BRCA1 Mutations In Women Research Articles

Prevalence of Germline Pathogenic BRCA mutations in women with High grade Serous ovarian cancers

Prevalence of Germline Pathogenic BRCA mutations in women with High grade Serous ovarian cancers

Abstract P5-03-17: BRCA1/2 gene mutations in patients with high-risk breast cancer in a tertiary-level hospital in Guatemala

Abstract Objectives, to stablish the frequency of BRCA1/2 mutation rate in high-penetrance breast cancer susceptibility population Methods Based on NCCN guidelines for testing criteria for high-penetrance breast cancer susceptibility genes genetic counseling was offered to 140 breast cancer patients in the hemato-oncology unit of Roosevelt Hospital at Guatemala City performing test with NGS and MLPA technology from 2019 to 2021. Results The overall BRCA1/2 mutation rate high-risk patients were 23% (33/140). Of the patients with mutations, 66.6% (22/33) had BRCA1 mutation, 33.3% (11/33) had BRCA2 mutation, of the mutated population the median age was 45 years. Regarding the phenotype in the mutated population, 75% were triple negative, 16% luminal and 9% with Her2 overexpression. Of the patients carrying the BRCA1 mutation, we identified the c.212+1G>A mutation in 40% of the patients, possibly a founder mutation. In the triple negative population and under 45 years of age, the percentage of patients with BRCA 1/2 mutation is 40.9 (88.8% BRCA1 and 11.1% BRCA2). Conclusions: we found a percentage of BRCA 1/2 mutations in the selected population (NCCN criteria) similar to that reported in other Latin American countries, highlighting the high percentage of BRCA mutations in women under 45 years with triple negative phenotype, previous reports have highlighted the frequency of the c.212+1G>A mutation of BRCA1 in breats cancer patient in Guatemala, in this study 40% of the BRCA1 mutations correspond to said mutation, considering it as a probable founder mutation. Citation Format: Juan Alvarado-Muñoz, Agatha Reyes-Morales, Marco Chivalan, Silvana Torselli, Hector Valenzuela, Gozalo Yalibat, Mario Ordoñez, Rosa León, Egly Alvarez. BRCA1/2 gene mutations in patients with high-risk breast cancer in a tertiary-level hospital in Guatemala [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-03-17.

Cost-minimization analysis of germline and somatic testing strategies for BRCA mutations in women with newly diagnosed epithelial ovarian cancer

Objective: The SOLO1 trial made it a priority to identify BRCA germline and somatic mutations in women with newly diagnosed epithelial ovarian cancer in order to determine candidates for olaparib maintenance. It is also important to differentiate between germline and somatic mutations because of the potential for cascade testing in relatives. Three testing strategies can be employed: (1) test all patients for germline mutations with reflex somatic testing if germline testing is negative; (2) test all tumors for somatic mutations with reflex germline testing if somatic testing is positive; or (3) perform simultaneous germline and somatic testing.

Association of Cytokeratin 5 and Claudin 3 expression with BRCA1 and BRCA2 germline mutations in women with early breast cancer

BackgroundIt is important to identify biomarkers associated with BRCA mutation in women with early breast cancer (BC) to improve early identification of mutation carriers. Thus, in this study, we examined the protein expression of claudin (CLDN) 3, CLDN4, CLDN7, and E-cadherin. Moreover, we analyzed additional histopathological variables and their associations in familial BC.MethodsImmunohistochemical analysis for CLDNs and E-cadherin was performed on 237 BC cases of three different subsets of BC tumors: 62 from BRCA1 mutation carriers, 59 from BRCA2 mutation carriers, and 116 tumors from patients with BRCA wild type (WT) as controls. Histopathological data were also analyzed in the different subgroups. Logistic regression and receiver operation characteristic (ROC) curve were conducted to investigate factors associated with BRCA tumors.ResultsExpression of CLDN3 positively correlated with BRCA-mutated BC. CLDN3 was expressed in 58% of BRCA1-mutated tumors compared to only 7% in BRCA2-mutated tumors (p < 0.001) and 1% in WT tumors (p < 0.001). CK5 and CK14 expression were also more likely to arise in BRCA1 tumors (44 and 16%, respectively) than in the control group (8 and 4%) (p < 0.001, p = 0.012, respectively). We also found a significantly higher proportion of CK5+ among BRCA1 tumors (44%) in comparison with BRCA2-related BC (8%) (p < 0.001). In addition, there was a significant difference between both groups regarding CK14: positive expression in 16 and 5%, respectively (p = 0.030). CK5 and CK14 did not differ between the BRCA2 group and the WT tumors significantly. In a multivariate regression model, expression of CK5 (Odds ratio (OR): 6.46; 95% confidence interval (CI): 1.52–27.43; p = 0.011), and CLDN3 (OR: 200.48; 95% CI: 21.52–1867.61; p < 0.001) were associated with BRCA1 mutation status.ConclusionsOur data suggests that CLDN3, CK5, and CK14 in combination with ER, PR and HER2 are associated with BRCA1 mutation status.

Knowledge Level and Educational Needs of Turkish Oncology Nurses Regarding the Genetics of Hereditary Breast and Ovarian Cancer.

This study evaluated Turkish oncology nurses' knowledge and educational needs regarding genetics of hereditary breast and ovarian cancers. An online survey was used to collect data from 104 Turkish oncology nurses. The mean level of knowledge in oncology genetics was 6.74 ± 3.85. The majority of nurses (78.7%) were aware of the fact that family history of ovarian or breast cancer is an important risk factor for ovarian or breast cancer; however, a much smaller percentage (25.5%) understood that BRCA1 mutations in women can be transferred by the father. The majority of the nurses (59.6%) were willing to take continuing education in cancer genetics. Turkish oncology nurses have a moderate level of knowledge in cancer genetics. Therefore, educators should develop targeted educational activities in genetics as a part of continuing education programs to enhance nursing practice in cancer care. J Contin Educ Nurs. 2017;48(12):570-576.

BRCA population screening for predicting breast cancer: for or against?

The pathogenesis of breast cancer, the most frequent female malignancy, entails both genetic and acquired risk factors. Among the various oncogenetic mutations, those involving the BReast Cancer 1 (BRCA1) and BReast Cancer 2 (BRCA2) genes are associated with an extremely high risk of developing breast cancer, with a penetration approximating 70% in women with a positive family history for this malignancy. This important evidence elicits some pragmatic considerations, such as the clinical effectiveness of screening for the most penetrant BRCA mutations in women with or without a positive familial history, but also raises important issues related to the most appropriate clinical management of these patients. Despite it seems now almost certain that BRCA testing should be offered to women with a positive familial history for breast cancer, the balance between advantages and limitations of a population screening remains largely debated. Whatever conclusion can be reach at this point in time must be accurately weighed against at least four different perspectives, which include the low prevalence of these mutations in the general population, the relatively lower risk of developing breast cancer in women without a familial history for this malignancy, the direct and indirect cost of genetic testing and, last but not least, the many potential psychological and clinical consequences in patients receiving a positive test result. Many of these still unresolved issues will be tentatively discussed in this article.

The Consequences of a BRCA Mutation in Women.

The Consequences of a BRCA Mutation in Women.

PCN168 - Cost-Effectiveness Analysis of Testing for Brca Mutations in Women Diagnosed with Ovarian Cancer and their Female First-Degree Relatives: A Uk Health Service Perspective

PCN168 - Cost-Effectiveness Analysis of Testing for Brca Mutations in Women Diagnosed with Ovarian Cancer and their Female First-Degree Relatives: A Uk Health Service Perspective

&lt;b&gt;Risk assessment for breast cancer and BRCA mutations in women with personal and familial history&lt;/b&gt; - doi: 10.4025/actascihealthsci.v35i2.12134

Risk estimation tools can be used in clinical practice to promote the counseling, prevention, or increase the surveillance against breast cancer development. The present study aimed to estimate the risk for breast cancer and the odds for BRCA1/2 mutations, and to correlate the values found by the different models. Breast cancer risk was determined by the models of Gail, Claus, BRCAPRO and Boadicea; and for the mutations, Myriad II, Penn II BRCAPRO, and Boadicea models were utilized, in women who have or had the disease (n = 16) and their respective first degree female relatives unaffected (n = 25). Considering non affected women 16% were categorized as high risk for breast cancer development in five years by the Gail model, and all values presented significant correlation among the models (p &lt; 0.05). Among the participants, 12% (5/41) were considered high risk for BRCA mutations. All the models presented significant correlation between the odds of BRCA1/2 mutation risk, except between Myriad II and Boadicea models. Since there is no model that includes all the variables influencing the development of this disease, it is essential to estimate the risk by more than one model before initiating any clinical intervention.

Comparison of BRCA1/2-positive and -negative women diagnosed with metachronous breast and ovarian cancers.

1546 Background: After a primary breast cancer (BC) or ovarian cancer (OC) diagnosis, women have a risk to develop a second primary cancer, significantly more so in women with a BRCA gene mutation. The objective was to evaluate characteristics of BRCA positive and negative women diagnosed with metachronous BC and OC. Methods: Women with metachronous BC and OC were identified at the University of Texas MD Anderson Cancer Center. BRCA test results, age at diagnosis of both BC and OC, first degree relatives (FDR) with BC and/or OC, total relatives affected, and histopathologic tumor features were obtained from a prospectively maintained research database. Univariate and logistical regression analyses were performed. Results: A total of 64 women with metachronous primary cancers underwent BRCA genetic testing. Of the 45 BRCA positive women, 36 (80%) were diagnosed with BC (mean 40 years) prior to OC and 9 (20%) were diagnosed with OC first (mean 47 years). Of the 19 BRCA negative women, 10 (53%) were diagnosed with BC first (mean 63 years), and 9 (47%) diagnosed with OC first (mean 48 years). Women diagnosed with BC first were more likely to be BRCA positive than women diagnosed with OC first (p=0.03). Patients with a FDR with BC were more likely BRCA positive than women without family history (p=0.0062). Patients with PR negative BR (p=0.0199) or triple negative (TN) BC (p=0.0139) were more likely to test BRCA positive. High grade ovarian carcinomas approached significance (p=0.053) in BRCA positive when compared to BRCA negative cohort. Ethnicity, total number of affected relatives with BC or OC, ER status, Her2 status, and nuclear grade were not statistically significant between the two groups. Conclusions: Women with OC preceding their BC with lack of family history of BC and OC are significantly less likely to test BRCA positive. BC is often the sentinel cancer in women with a BRCA mutation compared to BRCA negative women with metachronous BC and OC. This should be considered during the risk assessment to more accurately estimate the chance of identifying a BRCA mutation in women with metachronous BC and OC.

Prevalence of BRCA1 mutations in women with triple-negative breast cancer: A systematic review.

181 Background: We have reported a strong association between “triple-negative” breast cancer (TNBC) [estrogen receptor (ER) and progesterone receptor (PR) negative, HER2 negative] and the risk of having BRCA1 mutations in a meta-analysis. We hereby present a systematic review of a larger pool of specific data investigating the overall prevalence of BRCA1 mutations in women with TNBC. Methods: A Medline search combining the MeSH terms “BRCA” and “triple” and “negative” yielded 37 articles. A similar search in ASCO abstracts yielded 18 relevant articles. Prevalence in each study population as well as the overall prevalence was calculated. Results: 13 eligible studies (from year 2006 to 2011) including 1075 women with TNBC were identified. Out of 13, 1 study each was carried out on Ashkenazi Jewish and Hong Kong Chinese women respectively. Overall prevalence of BRCA1 mutations in women with TNBC is 20.93% (225 out of 1075) (range = 4.8%–43%). Ashkenazi Jewish women with TNBC have a higher-than-average prevalence of BRCA1 mutations (29.2%) although it is lower than the prevalence rates of some study populations. A remarkably low prevalence rate of BRCA1 mutations (4.8%) is found in Chinese women with TNBC. Conclusions: In view of the overall high prevalence rate of BRCA1 mutations (20.93%) in women with TNBC, genetic testing should be discussed with patients with TNBC. Further studies are suggested to evaluate the molecular basis of interestingly low BRCA1 prevalence (4.8%) in Chinese patients with TNBC.

Risk of having BRCA mutations in women with triple-negative breast cancer: A systematic review and meta-analysis.

160 Background: Increased prevalence of BRCA1 mutations (BRCA1) has been associated with the occurrence of triple-negative breast cancer (TNBC) (estrogen receptor [ER]- and progesterone receptor [PR]-negative, HER2-negative) in independent clinical studies. However, BRCA2 mutation (BRCA2) has not been found to overrepresent in women with TNBC. We have performed a meta-analysis of these studies to provide further statistical evidence of the association between BRCA positivity and TNBC. Methods: A Medline search of the MeSH terms “BRCA”, “triple”, and “negative” yielded 37 articles. A search of ASCO abstracts yielded 18 relevant articles. Random effects model was used for analysis due to heterogeneity among the proportions of included studies (Cochran’s Q = 18.52 and 15.18, tau2 = 0.61 and 1.29, I2 = 73% and 80% for BRCA1 and BRCA2 respectively). Mantel-Haenszel method was applied to calculate the pooled event-based odds ratio (OR) with 95% confidence interval (CI). Results: 6 studies including 1,602 BC patients were eligible for analysis of BRCA1 and 4 studies including 1297 BC patients for BRCA2. 172 patients with BRCA1 mutations and 79 patients with BRCA2 mutations were analyzed. Among these 6 studies, 1 included Ashkenazi Jewish women exclusively and 1 included only women of Chinese descent. The overall prevalence of BRCA1 was 10.05% (172 out of 1,602), and for TNBC patients 21.94% (95 out of 433) with an odds ratio of 5.90 (CI: 2.75, 12.66, p &lt; 0.00001). TNBC was not a risk for BRCA2 (OR = 0.67, CI: 0.19, 2.39, p = 0.53). Chinese women with TNBC did not have an elevated risk of BRCA1 (OR = 0.94, CI: 0.24, 3.66) in contrast to Jewish women with TNBC who had the highest risk of BRCA1 among the populations studied (OR = 21.79, CI: 9.03, 52.55). Conclusions: Women with TNBC carry a significantly high risk of having BRCA1 but not BRCA2 mutations. We recommend genetic testing for BRCA1 mutations in women with TNBC especially in Ashkenazi Jewish population. Further studies on Chinese population are needed to further establish the relationship between TNBC and BRCA1 mutations in this cohort.

Management of Women With BRCA Mutations

Ms E, a 41-year-old BRCA1 mutation carrier, was diagnosed 4 years ago as having breast cancer and opted for breast-conserving therapy. Prior to receiving chemotherapy, she harvested her eggs through in vitro fertilization and subsequently used preimplantation genetic diagnosis; 3 months ago she delivered a healthy boy. This review examines the prevalence of BRCA mutations in women with breast cancer, as well as current recommendations for surgery and systemic therapy in these women. In particular, the risk of a contralateral breast cancer is reviewed to help guide the choice of prophylactic mastectomies vs breast-conserving therapy. The technology of preimplantation genetic diagnosis and genetic testing in relatives of mutation carriers is discussed.

BRCA1 mutations in women with familial or early-onset breast cancer and BRCA2 mutations in familial cancer in Estonia

BackgroundThe aim of this study was to identify BRCA1 and BRCA2 mutations in the Estonian population. We analyzed genetic data and questionnaire from 64 early-onset (< 45 y) breast cancer patients, 47 familial cases (patients with breast or ovarian cancer and a case of these cancers in the family), and 33 predictive cases (patients without breast or ovarian cancer, with a family history of such diseases) from Estonia for mutations in the BRCA1 gene. A sub-set of familial cases and predictive cases were also analyzed for mutations in the BRCA2 gene.MethodsFor mutation detection, we used the Polymerase Chain Reaction-Single Stranded Conformation Polymorphism Heteroduplex Analysis (PCR-SSCP-HD), followed by direct DNA sequencing.ResultsWe identified three clinically important mutations in the BRCA1 gene, including seven occurrences of the c.5382insC mutation, three of c.4154delA, and one instance of c.3881_3882delGA. We also detected six polymorphisms: c.2430T>C, c.3232A>G, c.4158A>G, c.4427T>C, c.4956A>G, and c.5002T>C. Four sequence alterations were detected in introns: c.560+64delT, c.560+ [36-38delCTT, 52-63del12], c.666-58delT, and c.5396+60insGTATTCCACTCC. In the BRCA2 gene, two clinically important mutations were found: c.9610C>T and c.6631delTTAAATG. Additionally, two alterations (c.7049G>T and c.7069+80delTTAG) with unknown clinical significance were detected.ConclusionsIn our dataset, the overall frequency of clinically important BRCA1 mutations in early-onset patients, familial cases, and predictive testing was 7.6% (144 cases, 11 mutation carriers). Pathogenic mutations were identified in 4 of the 64 early-onset breast cancer cases (6.3%). In familial cases, clinically important mutations in the BRCA1 gene were found in 6 of the 47 individuals analyzed (12.8%). In predictive cases, 1 clinically important mutation was detected in 33 individuals studied (3%). The occurrence of clinically important mutations in BRCA2 in familial cases of breast cancer was 2 of the 16 individuals analyzed (12.5%).

Counseling for male BRCA mutation carriers – a review

BRCA mutations in women confer a high risk for breast and ovarian cancers. The risks to male carriers are poorly understood and risk management strategies undescribed. This review summarizes current evidence and gives recommendations for counseling male BRCA mutation carriers. Reported risks for breast, prostate, pancreatic, gastric and hematologic cancers are higher in male BRCA mutation carriers vs non-carriers. Especially in male BRCA2 mutation carriers under age 65 prostate and pancreatic cancer risks are increased. The risk increase for primary cancers of organs like the liver, bone and brain is difficult to assess as these organs are common sites for metastases. Reports on colorectal cancer and melanoma risks are inconclusive. On the current limited evidence available, male BRCA mutation carriers should be regarded as at high risk for breast, prostate, gastric, pancreatic and colorectal cancers; surveillance by appropriate investigations should start at age 40 years.

BRCA1 germline mutations and tumor characteristics in Chinese women with familial or early-onset breast cancer

The data related to BRCA1 germline mutation in Chinese women with familial breast cancer is increasing. However, little is known the frequency of BRCA1 mutations in Chinese women with familial or early-onset breast cancer from Northern China, and few studies are available to investigate the clinicopathological characteristics of BRCA1 tumors in Chinese women. In this study, we detected germline mutations in BRCA1 in a cohort of 139 breast cancer patients who either have a family history of breast cancer (n = 68) or whose tumors are diagnosed at or before the age of 35 (n = 71) from Northern China. A total of 6 deleterious BRCA1 mutations were identified in this cohort, 4 of which (5587-1 del8, 3887 del AG, IVS21 + 1delG, and 2129 ins TG) are novel and one mutation (3478del5) detected in this study was only reported in Chinese population. The frequency of BRCA1 mutations in women with familial or early-onset breast cancer was 5.9% (4/68) or 2.8% (2/71) in this cohort, respectively; but the mutations were detected in 4 of 16(25.0%) familial breast cancer patients whose tumors were diagnosed before the age of 40. Moreover, BRCA1 mutation tumors tended to be high histological grade, and to be negative for ER, PgR, and Her-2 compared with tumors without BRCA1 mutations. Our study suggests that Chinese women with a family history of breast cancer whose tumors are diagnosed before age of 40 would be a suitable candidate for BRCA1 testing; and BRCA1 tumors in Chinese women exhibit an aggressive phenotype.

Estimating risk of breast cancer in carriers of BRCA1 and BRCA2 mutations: a meta‐analytic approach

Estimates of penetrance (or risk) of breast cancer among BRCA mutation carriers in published studies are heterogeneous, prohibiting direct combined estimates. Estimates of prevalence of BRCA mutations are more homogeneous and could allow combined estimates of prevalence. We propose a combined estimator of penetrance from combined estimates of the prevalence of BRCA mutations in women with and without breast cancer and from the probability of breast cancer by using Bayes' Theorem. The relative risk of having breast cancer with positive family history and the prevalence of positive family history contribute to the combined estimate of penetrance if family history is present. The combined estimate incorporates variation in estimates from different resources. The method is illustrated by using data from Ashkenazi Jewish women unselected for family history and for those with family history. Risks of breast cancer conferred by BRCA1 and BRCA2 mutations are estimated to be 8.39 per cent (6.56, 10.68 per cent) and 2.66 per cent (1.85, 3.82 per cent) by 40 years old, and 47.45 per cent (37.39, 57.72 per cent) and 31.85 per cent (23.72, 41.26 per cent) by 75 years old, respectively. For those with family history, risks of breast cancer conferred by BRCA mutations appear to be higher.

BRCA1 mutations in ovarian cancer and borderline tumours in Norway: a nested case-control study.

The aims of the present study were to find the frequency of the most common BRCA1 mutations in women with ovarian tumours identified from a population-based cancer registry and in the general population, to estimate the relative risk of ovarian tumours among the mutation carriers, and to explore the value of using CA125 as a prediagnostic test. The study was designed as a nested case–control study within a cohort mainly consisting of participants in population-based health examinations. The data files of The Cancer Registry of Norway and the Janus serum bank were linked to identify cases with ovarian cancer and borderline tumours. Hereditary BRCA1 mutations were determined using archived serum samples and capillary electrophoresis. Altogether 478 ovarian cancer patients and 190 patients with borderline tumours were identified, and 1421 and 568 matching controls were selected. Odds ratios (OR) of developing ovarian cancer and borderline tumours in the presence of BRCA1 mutations and CA125 level were derived from conditional logistic regression models. Among the 478 ovarian cancer patients, 19 BRCA1 mutations were identified (1675delA, 1135insA, 816delGT and 3347delAG), none among the patients with borderline tumours. Only two of the 1989 controls were BRCA1 mutation carriers (0.10%). The risk of ovarian cancer among the mutation carriers was strongly elevated (OR=29, 95% CI=6.6–120). CA125 was a marker for ovarian cancer, but the sensitivity was low. This study showed that BRCA1 mutation carriers have a very high risk of ovarian cancer. However, since the prevalence of BRCA1 mutations in the Norwegian population was low, the proportion of ovarian cancers due to BRCA1 mutations seemed to be low, about 4%. The sensitivity of using CA125 only as a screening test for ovarian cancer was low.

Primary peritoneal serous papillary carcinoma: A new epidemiologic trend? A matched-case comparison with ovarian serous papillary cancer

The aim of the study was to examine the prevalence of primary peritoneal serous papillary carcinoma (PPSPC) as compared with ovarian serous papillary cancer (OSPC), and to study the clinicopathologic features and the frequency of germline BRCA1and BRCA2mutations in patients with PPSPC compared with those with OSPC. The study group included 28 cases of PPSPC. The comparison group included 35 female patients with OSPC, matched for stage, grade, and histologic subtype. All tumors were staged as either IIIB, IIIC or IV according to FIGO criteria. The patient characteristics, family and personal history of malignancies, the prevalence of germline BRCA mutations, clinicopathologic findings, presenting symptoms, pre- and intraoperative findings, and survival were compared in a matched-case retrospective study comparing patients with PPSPC vs. those with OSPC. Statistical analysis was made using Student'st-test, Chi-square, Wilcoxon, Kaplan-Meier and log-rank methods. Women with PPSPC had a significantly earlier menarche (P= 0.037) and a higher number or births (P= 0.03) than women with OSPC. No difference was found with regard to the prevalence of germline BRCA mutations in women with PPSPC compared with women with OSPC (7.1% vs. 25.7%). There was a significant increase (P= 0.02) in the incidence of abdominal distension as reported by PPSPC (64%) vs. OSPC patients (26%). Significantly more women with PPSPC than with OSPC presented with clinical ascites (P= 0.0001) and without palpable pelvic mass (P= 0.000001). On exploratory laparotomy, significantly more women with PPSPC than with OSPC had a minimal disease in the pelvis (P= 0.0087). Three-year survival analysis demonstrated a significantly worse survival rate for the PPSPC group than for the OSPC group (P= 0.017). A significant increase in the prevalence of PPSPC compared with OSPC was observed during the study years (P= 0.00001). We concluded that PPSPC and OSPC might be two distinct cancers, presenting a new epidemiologic trend regarding the increased incidence of PPSPC.

P53 and WAF1 polymorphisms in Jewish-Israeli women with epithelial ovarian cancer and its association with BRCA mutations.

To investigate whether polymorphic p53 and WAF1 alleles are associated with clinical, demographic and histopathological features and BRCA mutation in women with ovarian cancer. A cross-sectional study. Two hundred and twenty-one nonselected Israeli women with epithelial ovarian cancer. DNA was analysed for known polymorphisms in intron 3 (a 16 nucleotide single repeat) and intron 6 (a G to A change at nucleotide 13,494) of the p53 gene, the S31R polymorphism in the WAF1 gene, and for three predominant Jewish mutations in the BRCA genes (185delAG and 5382insC in BRCA1, and 6174delT in BRCA2). The rate of polymorphic p53 and WAF1 alleles and their association with BRCA mutation, ethnic origin, age and stage at diagnosis, and family history of cancer. Of the tested women, 72 (32.6%) were either BRCA1 (n = 57) or BRCA2 (n = 15) mutation carriers. Sixty-eight of 213 (31.9%) were heterozygous for intron 3 polymorphism, 67/193 (34.7%) for intron 6 polymorphism, and 22/154 (14.3%) for S31R of the WAF1 gene. The p53 and WAF1 polymorphism rate did not differ between BRCA mutation carriers and noncarriers. No significant association between specific p53 or WAF1 genotypes, and clinical, histopathological or demographic variables was observed. In Jewish-Israeli women with sporadic and familial ovarian cancer, p53 or WAF1 polymorphisms do not seem to affect the phenotype.