Analyses of p53 expression pattern and BRCA mutations in patients with double primary breast and ovarian cancer.

OBJECTIVE: To analyze the somatic pattern of p53 expression and BRCA germline mutation status in Israeli patients with both ovarian (OvCa) and breast cancer (BrCa). METHODS: The study group comprised 43 Israeli patients with OvCa, all of whom had previous primary BrCa. p53 immunohistochemistry (IHC) on all available archival tissues and genotyping for the three predominant Jewish germline BRCA1-2 mutations were carried out. Samples from 64 patients with solitary OvCa and 61 with solitary BrCa were similarly analyzed as controls. RESULTS: p53 expression pattern and the immunopositivity rate were similar in the ovarian and breast tumors within the study group and in the two control groups: positive p53 staining was detected in 68% of ovarian tumors in the study group compared with 71.9% in the controls, and in 19.4% of the BrCa tissues versus 21.3% in the controls. Within the study group, advanced stage OvCa had a higher rate of p53 expression (84%) compared to early stage disease (38.5%) (P = 0.006). This difference was not apparent in the solitary OvCa control group. OvCa in BRCA1-2 mutation carriers from the study group were more likely to display positive p53 staining (79%), especially in tumors diagnosed before the age of 60 (90%) compared with the OvCa of noncarriers (60%), but this difference was statistically insignificant. The p53 expression rate in BrCa samples from the study group was not associated with BRCA1-2 mutation status. CONCLUSIONS: Positive p53 expression, detected by IHC, in OvCa patients with previous primary BrCa is significantly higher in advanced stage disease in BRCA1-2 mutation carriers. There is a higher positive p53 expression somatically in OvCa in BRCA1-2 carriers in whom OvCa was diagnosed before the age of 60 years, although this trend is not statistically significant. These observations suggest that somatic p53 inactivation may be an important event in ovarian tumorigenesis in this subset of patients.

A possible genetic factor in the pathogenesis of ovarian dermoid cysts.

This study was undertaken in order to evaluate a possible genetic influence on the pathogenesis of ovarian dermoid cysts. We have performed a case-control study comparing the prevalence of a history of dermoid cysts in first-degree relatives of women with dermoid cysts and among first-degree relatives of women without dermoid cysts. The study group included 285 women with an established diagnosis of ovarian dermoid cysts. The control group included 378 women with sonographically normal ovaries. To assess the relationship between a first-degree family history of dermoid cysts and the diagnosis of ovarian dermoid cysts, a multivariate stepwise logistic regression model was applied. In 28 families of the study group (9.8%), a dermoid cyst was found in at least 1 first-degree relative as compared with only eight families (2%) among the controls (adjusted odds ratio -5.60; 95% CI 2.24-14.2). The data suggest a genetic predisposition towards dermoid cysts which merits further exploration.

Population attributes affecting the prevalence of BRCA mutation carriers in epithelial ovarian cancer cases in israel.

OBJECTIVE: The objective was to evaluate the prevalence of BRCA1/2 mutations in selected categories of ovarian cancer patients in Israel. METHODS: Blood samples and specimens of ovarian tumors were obtained in the course of a national case control study of women with ovarian cancer in Israel. Eight hundred ninety-six patients with epithelial ovarian cancer, 40 cases with nonepithelial ovarian cancer, and 68 with primary peritoneal cancer were tested for the BRCA mutations. Analysis of the three common BRCA mutations in Israel (185delAG, 5382insC in BRCA1, and 6174delT in BRCA2) was done using a multiplex polymerase chain reaction assay. A multivariate logistic regression model was used to assess the association of mutation carrier status and other factors (age, origin, family history, and clinical variables). RESULTS: Of the 779 invasive epithelial ovarian cancer cases, 29.4% were mutation carriers. The prevalence of the mutations was higher among women below age 60 and in more advanced cases. The prevalence was low in mucinous tumors. There was almost a twofold excess of mutations among women with positive family history (45.7%), but still 26.5% of the family history negative cases were carriers. As expected, we found a higher rate of mutation carriers among the Ashkenazi group (34.2%) and 55% among Ashkenazi women with positive family history. No subjects born in North Africa were mutation positive. CONCLUSION: BRCA mutations are strongly associated with ovarian cancer and they are present in variable rates in distinct age, ethnic, and histopathologic categories.

The possible association between in vitro fertilization treatments and cancer development.

The objective of this paper is to assess whether ovarian hyperstimulation and in vitro fertilization (IVF) are associated with increased risk of cancer development, using an historical cohort analysis of infertile women who attended the IVF unit, Lis Maternity Hospital Tel Aviv Medical Center, Tel Aviv, Israel. One thousand and 82 women participated in the IVF treatment program between 1984 and 1992. Cancer incidence rates were determined through the National Cancer Registry and were compared to the expected rates with respect to appropriate age and continent of birth. Twenty-one cases of cancer were observed as compared to 11 that were expected (SIR 1.91; 95% CI 1.18-2.91). When cancer cases that were diagnosed within one year of the IVF treatment were excluded from the analysis (SIR = 1.46; 95% CI 0.83-2.36), no significant excess risk of cancer was noted. We conclude that in this cohort of infertile women, the higher than expected cancer rate could not be attributed to IVF treatments. Special attention should be made to women who may be diagnosed with cancer during or shortly after IVF treatment.

Body mass index at age 18 years and during adult life and ovarian cancer risk.

During the years 1994-1999, a nationwide ovarian cancer case-control study was conducted in Israel. The present analysis addresses the question: Is epithelial ovarian cancer associated with body mass index at age 18 years and/or with weight changes in body mass index between adolescence and adult life? The study is based on 1,269 women with epithelial ovarian cancer and 2,111 matched controls. A significant decrease in risk of ovarian cancer was observed with parity, oral contraceptive use, and postmenopausal status. A significant increase in risk with family history of ovarian/breast cancer was also found. No significant association with age at menarche or infertility was found. For body mass index at age 18 years, the odds ratio of the highest versus lowest body mass index quartile was 1.42 (95% confidence interval: 1.08, 1.85) and after adjusting for confounders was 1.54 (95% confidence interval: 1.17, 2.02). However, no statistically significant risk associated with change in weight from age 18 years to adult life was found. The authors conclude that, in their population, body mass index at age 18 years is an independent risk factor for ovarian cancer.

Frequency of BRCA mutations in primary peritoneal carcinoma in Israeli Jewish women.

OBJECTIVE: The aim of the present study was to compare demographic and clinical characteristics of primary peritoneal carcinoma (PPC) to ovarian carcinoma (OvC) with regard to BRCA mutation frequencies. METHODS: Incident cases of histologically confirmed cancer of the ovary or peritoneum diagnosed in Israeli Jewish women between March 1, 1994, and June 30, 1999, were identified within the framework of an ongoing nationwide epidemiological study of these neoplasms in Israel. The present study comprises 609 (81.5% of 747) Jewish women with epithelial stage III-IV OvC and 68 (77.3% of 88) Jewish women with PPC who were genetically tested for the BRCA mutations. Data from each patient were collected by the aid of a prestructured questionnaire and medical records. Blood samples or tumor tissue was tested for the 185delAG and 5382insC mutations in BRCA1 and the 6174delT mutations in BRCA2. RESULTS: A carrier rate of 28% of any BRCA 1/2 mutation was observed among the PPC group and of 30% among the invasive stage III-IV OvC. No differences were found between PPC and OvC neither in the overall distribution of BRCA1/2 mutation carrier rates nor according to type of mutation, age, ethnic origin, and histologic subtype. Among women with a positive family history, a higher rate of mutation carriers was observed in the PPC group compared to the OvC group (72.7 vs 43.8%, respectively, P = 0.07). CONCLUSIONS: The similar frequency distribution of BRCA1/2 mutations in PPC and OvC observed in the present study indicates that these mutations may predispose to PPC as well and that this neoplasm is part of the hereditary breast-ovarian cancer syndrome.

Social factors and mortality in the old-old in Israel: the CALAS study.

OBJECTIVES: Using a theoretical framework that divided social factors measures into structure, function, and social engagement, this study determined those aspects of social networks most significantly associated with 8-year, all-cause mortality among the old-old in Israel. METHODS: Jews (n = 1,340) aged 75-94 living in Israel on January 1, 1989, were randomly selected from the National Population Register; stratified by age, sex, and place of birth; and interviewed in person. Mortality was determined according to the National Death Registry (December 1997). RESULTS: After controlling for sociodemographics and measures of health, cognitive status, depressive symptoms, and physical function, the measures of social engagement that explicitly involved others were associated with a lower risk of mortality. No measure of the function of the social network was associated with risk of mortality. Living in the community without a spouse and with a child and living in an institution were significantly associated with a higher risk of mortality. DISCUSSION: The finding that participating in activities with people outside of the immediate family is associated with a lower risk of death has practical implications for helping the aging population and their families in their decision-making process. Lack of support for the hypothesis that those with more social support would show reduced risk of mortality may indicate that the positive effect of perceiving support and the negative effect of needing support may cancel each other out and result in no perceived effect. In this population, the association between socioeconomic status (SES) and the risk of mortality seems to be expressed through the living arrangements, with the sick and frail, both in institutions (higher SES) and in the community with a child or other (lower SES), having a higher risk of mortality. These findings are consistent with the use of children as a substitute for institutionalization, and imply that at least some cohabitation was the caretaking solution for the noninstitutionalized old-old who were of low SES, frail, and close to death.

Effect of BRCA mutations on the length of survival in epithelial ovarian tumors.

PURPOSE: To study the role of BRCA mutations in ovarian cancer survival. PATIENTS AND METHODS: Blood samples and specimens of ovarian tumors (whenever blood samples were not available) at the time of the primary surgery were obtained in the course of a nationwide case-control study of women with ovarian cancer in Israel. The three common BRCA mutations in Israel (185delAG, 5382insC, and 6174delT) were analyzed with a multiplex polymerase chain reaction to amplify the exons containing the three mutations using fluor-labeled primers in a single reaction. Because each mutation is a small insertion or deletion, they can be detected as length polymorphisms. Patients were followed for up to 5 years (range, 20 to 64 months). Statistical analysis was performed using the Kaplan-Meier method and the log-rank test. Stepwise Cox regression analysis was used for determination of independent prognostic factors. RESULTS: This report is based on 896 blood or tumor specimens analyzed for the presence of the BRCA mutations. Of these, 234 women (26.1%) were found to be positive. A significant difference in survival pattern was found between BRCA1/BRCA2 carriers and noncarriers among the women with invasive ovarian cancer (median survival, 53.4 months v. 37.8 months; 3-year survival, 65.8% v. 51.9%, respectively). These differences were independent of age at diagnosis or stage of the disease. CONCLUSION: Our data indicate that the survival of patients with ovarian cancer is affected by BRCA germline mutation, at least in the early years after diagnosis.

A single nucleotide polymorphism in the 5' untranslated region of RAD51 and risk of cancer among BRCA1/2 mutation carriers.

RAD51 colocalizes with both BRCA1 and BRCA2, and genetic variants in RAD51 would be candidate BRCA1/2 modifiers. We searched for RAD51 polymorphisms by sequencing 20 individuals. We compared the polymorphism allele frequencies between female BRCA1/2 mutation carriers with and without breast or ovarian cancer and between population-based ovarian cancer cases with BRCA1/2 mutations to cases and controls without mutations. We discovered two single nucleotide polymorphisms (SNPs) at positions 135 g-->c and 172 g-->t of the 5' untranslated region. In an initial group of BRCA1/2 mutation carriers, 14 (21%) of 67 breast cancer cases carried a "c" allele at RAD51:135 g-->c, whereas 8 (7%) of 119 women without breast cancer carried this allele. In a second set of 466 mutation carriers from three centers, the association of RAD51:135 g-->c with breast cancer risk was not confirmed. Analyses restricted to the 216 BRCA2 mutation carriers, however, showed a statistically significant association of the 135 "c" allele with the risk of breast cancer (adjusted odds ratio, 3.2; 95% confidence limit, 1.4-40). BRCA1/2 mutation carriers with ovarian cancer were only about one half as likely to carry the RAD51:135 g-->c SNP. Analysis of the RAD51:135 g-->c SNP in 738 subjects from an Israeli ovarian cancer case-control study was consistent with a lower risk of ovarian cancer among BRCA1/2 mutation carriers with the "c" allele. We have identified a RAD51 5' untranslated region SNP that may be associated with an increased risk of breast cancer and a lower risk of ovarian cancer among BRCA2 mutation carriers. The biochemical basis of this risk modifier is currently unknown.

Assistance with personal care activities among the old-old in Israel: a national epidemiological study.

OBJECTIVES: The objectives of this study were to (1) estimate rates of difficulty, need for assistance, and receipt of assistance with activities of daily living (ADLs) among the old-old in Israel; (2) describe the living arrangements of the dependent old-old; and (3) gain insight into the caregiving provided to the disabled members of this population. DESIGN: A random stratified sample of 1,820 subjects age 75 to 94 selected from the National Population Register (NPR), a complete listing of the Israeli population maintained by the Ministry of the Interior. The study sample consisted of Jews living in Israel on January 1, 1989, stratified by age (four 5-year age groups: 75-79, 80-84, 85-89, 90-94), sex, and place of birth (Europe-America, Middle East/North Africa, Israel). SETTING: National sample of old-old Jewish Israelis. PARTICIPANTS: One thousand eight hundred twenty Israelis age 75 to 94 who were living in the community or in institutions at the time of the baseline interview. MEASUREMENTS: Participants' disability status was classified in terms of difficulty with, needing help with, and receiving help with any of five ADLs (washing/bathing, dressing, transferring, toileting, and eating). Only those receiving assistance from a person (as opposed to a device) were considered to be receiving help. The independent variables used included sociodemographic, health, and social network characteristics of the participants. RESULTS: Twenty-one percent of those age 75 to 94 were found to be receiving personal assistance with at least one ADL. The most dependent were those age 90 to 94, women, those born in the Middle East or North Africa, and those living in an institution. Among those dependent in one or more ADLs, the overall community:institutionalized ratio was 2.4:1. Those who were dependent in three to five ADLs were about twice as likely to live in an institution as were those who were dependent in one or two ADLs. The Middle Eastern/North African born were more likely to be dependent, and at any given level of disability were more likely to be living in the community with a child and receiving the majority of their caretaking from the informal sector, primarily their family. CONCLUSION: We conclude that the families of disabled older people, particularly the Middle Eastern/North African born, provide a great deal of care for their older relatives despite the availability of a full range of services, providing no evidence of withdrawal of family care when state home and institutional care are available. This finding may imply underutilization of services, which should be investigated further to determine if it is caused by barriers to utilization or by the free choice of the disabled old-old and their families.

The Tyr978X BRCA1 Mutation in Non-Ashkenazi Jews: Occurrence in High-Risk Families, General Population and Unselected Ovarian Cancer Patients.

Background: In Jewish individuals of Ashkenazi (East European) decent, three predominant mutations, 185 delAG and 5382insC (BRCA1) and 6174delT (BRCA2), seem to account for a substantial portion of germline mutations in high-risk breast/ovarian cancer families. Among non-Ashkenazi Jews, the 185delAG and the Tyr978X mutations, as well as several 'private' mutations have been reported within the BRCA1 gene. Objective: Assessing the occurrence rate of the Tyr978X BRCA1 germline mutation in Jewish non-Ashkenazi individuals: high-risk familial cases, unselected ovarian cancer patients and the general average risk Jewish Iraqi population. In addition, finding proof that this is a founder mutation. Methods: PCR amplification of the relevant fragment of the BRCA1 gene from constitutional DNA followed by restriction enzyme digest that differentiates the wild type from the mutant allele. In addition, BRCA1-linked markers were used for haplotype analysis. Results: The Tyr978X BRCA1 mutation was detected in 3/289 (1%) of the average-risk Jewish Iraqi population, in 7/408 (1.7%) high-risk Jewish non-Ashkenazi individuals (representing 332 unrelated families) and in 1/81 (1.2%) of unselected Jewish non-Ashkenazi ovarian cancer patients. Allelotyping using BRCA1-linked markers revealed an identical allelic pattern in all mutation carriers with the intragenic markers. Conclusions: Our findings suggest that this mutation is prevalent in Iraqi Jews, represents a founder mutation, and should be incorporated into the panel of mutations analyzed in high-risk families of the appropriate ethnic background. Copyright 2001 S. Karger AG, Basel

Incidence of leukemia and other cancers in Down syndrome subjects in Israel.

Epidemiologic data have confirmed the high susceptibility of persons with Down syndrome (DS) to leukemia. The question of proneness to other kinds of cancer is still open. In this study we reassessed the incidence rates of leukemia and other malignancies in Israeli DS subjects, based on the total population. The target population consisted of all DS subjects in Israel in the period of 1948--1995. Due to incompleteness of data, the target population was not fully achieved, thus the study population was divided into 2 subgroups: subjects born in Israel between 1979 and 1995 (registry group) and currently or past-institutionalized subjects born before 1979 (institution group). The cohort was linked with the Cancer Registry, and cancer cases that had been diagnosed through December 1995 were subsequently identified. Observed incidence rates were compared with expected rates in the general population. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were computed for each disease category. Analyses were performed separately for each subgroup of the study population. In the registry group, 7 cancer cases were observed, compared with 1.5 expected (SIR = 4.67, 95% CI 1.9--9.6), all leukemia cases. For the institution group a total of 17 cancer cases were observed, compared with 12.8 expected. These included 4 cases of leukemia (SIR = 6.90, 95% CI 1.90--17.70). An excess of gastric cancer in male subjects (SIR = 11.9, 95% CI 1.3--42.9) was also observed. Significant excess of leukemia in DS population in Israel is in accordance with previously published data. An excess of gastric cancer in DS male subjects born before 1979, which has not been reported before, should be further explored.

Parity, oral contraceptives, and the risk of ovarian cancer among carriers and noncarriers of a BRCA1 or BRCA2 mutation.

BACKGROUND: Multiparity and the use of oral contraceptives reduce the risk of ovarian cancer, but their effects on this risk in women with a BRCA1 or BRCA2 mutation are unclear. METHODS: We conducted a population-based case-control study of ovarian cancer among Jewish women in Israel. Women were tested for the two founder mutations in BRCA1 and the one founder mutation in BRCA2 that are known to be common among Jews. We estimated the effects of parity and oral-contraceptive use on the risk of ovarian cancer in carriers and noncarriers in separate analyses that included all control women, who did not have ovarian cancer. RESULTS: Of 751 controls who underwent mutation analysis, 13 (1.7 percent) had a BRCA1 or BRCA2 mutation, whereas 244 of 840 women with ovarian cancer (29.0 percent) had a BRCA1 or BRCA2 mutation. Overall, each additional birth and each additional year of use of oral contraceptives were found to lower the risk of ovarian cancer, as expected. Additional births were protective in separate analyses of carriers and noncarriers, but oral-contraceptive use appeared to reduce the risk only in noncarriers; among carriers, the reduction in the odds of ovarian cancer was 12 percent per birth (95 percent confidence interval, 2.3 to 21 percent) and 0.2 percent per year of oral-contraceptive use (-4.9 to 5.0 percent). CONCLUSIONS: The risk of ovarian cancer among carriers of a BRCA1 or BRCA2 mutation decreases with each birth but not with increased duration of use of oral contraceptives. These data suggest that it is premature to use oral contraceptives for the chemoprevention of ovarian cancer in carriers of such mutations.

Physician visits, emergency room utilization, and overnight hospitalization in the old-old in Israel: the cross-sectional and longitudinal aging study (CALAS).

OBJECTIVES: The objective of this paper is to assess the risk factors for physician contact in the month before the interview (PM) and emergency room utilization (ERU) and overnight hospitalization (OH) in the year before the interview, through the use of the behavioral model as a conceptual framework. DESIGN: A random stratified sample of subjects age 75 to 94 was selected from the National Population Register (a complete listing of the Israeli population maintained by the Ministry of the Interior). The study sample consisted of Jews living in Israel on January 1, 1989, stratified by age (four 5-year age groups: 75-79, 80-84, 85-89, and 90-94), sex, and place of birth (Europe/America, Asia/Africa, and Israel). SETTING: Community-dwelling old-old Jewish Israelis. PARTICIPANTS: 1,487 people living in the community at the time of the baseline interview. MEASUREMENTS: The dependent variables were PM in the month before the interview and ERU and OH in the previous year. The independent variables were: predisposing variables (age, sex, place of birth, and education); enabling variables (income and the social network variables of marital status, living arrangements, and number of in-person contacts per week with any child); and need variables (number of self-reported chronic medical conditions, subjective health, depressive symptoms, number of difficulties with activities of daily living and instrumental activities of daily living, measures of physical robustness, and engaging in regular physical sportive activities). RESULTS: The predisposing and enabling factors were only minimally associated with utilization rates in the old old in Israel, with the exception of lower rates of ERU by those who were living alone. Age was not significantly associated with healthcare utilization in the old-old population studied. Healthcare utilization was found to be associated primarily with health and functional status. CONCLUSION: In a system of free and equal access to healthcare services, the demand for health services by a population with high levels of chronic disease and disability is driven primarily by health needs, rather than by extraneous factors such as income and education. The study indicates that equity in the provision of health services is attainable. Policy makers should provide for actual need, remove artificial barriers, and prepare accurate estimates of future needs.

Characteristics of clients attending confidential versus anonymous testing clinics for human immunodeficiency virus.

OBJECTIVES: To compare risk behavior between subjects attending anonymous and confidential clinics for human immunodeficiency virus testing, and to assess whether anonymous testing results in a higher accrual of persons at risk for HIV. METHODS: An anonymous questionnaire that addressed sociodemographic and risk behavior aspects was administered to 140 subjects attending an anonymous clinic and 124 attending a confidential clinic in the Tel Aviv area. A logistic regression analysis was used to compare the effects of various behavioral factors on the probability of attending each clinic. RESULTS: Chronological age, age at first sexual intercourse, and the percent of married subjects were similar in both clinics. However, there was a significant difference in the sex ratio and in educational attainment (85.0% versus 55.6% were males, P < 0.001; and 58% vs. 34% had over 12 years of education, P < 0.001, in the anonymous and confidential clinics respectively). There was a striking difference between the two clinics with regard to sexual experience characteristics: of the subjects reaching the anonymous clinic 21.4% were homosexual and 10.0% bisexual versus a total of 2.6% in the confidential clinic. A logistic regression analysis, comparing the effects of various behavioral factors on the probability of attending each clinic, showed that gender (male), high education, homosexuality, number of partners and sexual encounter with sex workers were the strongest predictors for selecting anonymous HIV examination. CONCLUSIONS: Individuals at high risk for HIV, such as homosexuals and bisexuals, prefer to attend an anonymous clinic.

Selectively increased risk of cancer in men with coronary heart disease.

Cancer incidence was assessed among a cohort of 10,923 male coronary patients in Israel screened for participation in a secondary prevention trial and compared with national cancer incidence rates. Higher total and age-specific incidence rates of cancer were observed among male coronary patients than among the Israeli male population, but this excess was limited to cancers of the lung, bladder, and colon.

A new approach to blood pressure measurement in the primary care setting.

In this study, a method of taking one blood pressure reading using a sphygmomanometer was compared with a method of taking multiple successive readings using an automatic device. With multiple readings the blood pressure tended to be lower and fewer patients were classified as hypertensive. Using an automatic blood pressure recording device seems to be a practical way of achieving multiple readings in a busy clinic setting.

Patients with double primary tumors in the breast and ovary- clinical characteristics and BRCA1-2 mutations status.

OBJECTIVE: The aim of this study was to define the prevalence, clinical characteristics, and BRCA1-2 mutation carrier status of ovarian cancer (OvC) patients with a previous primary malignancy in the breast (PPMBr). METHODS: The study population comprised 1240 consecutive Jewish Israeli women with pathologically confirmed epithelial OvC diagnosed between March 1, 1994, and December 31, 1997. Demographic and clinical data were obtained from medical files and from a detailed questionnaire taken through a nationwide epidemiological case-control study on OvC. Blood samples and tumor tissues were collected for analysis of the three predominant germline BRCA1-2 Jewish founder mutations (185delAG, 5382insC, and 6174delT). RESULTS: Fifty nine (4.7%) patients with OvC had a PPMBr. The median age at diagnosis of OvC was 60 years. The mean interval between the two diagnoses was 104 months (range 0-363 months). In the majority of the patients (n = 53), the diagnosis of breast cancer (BrC) preceded the OvC by more than 1 year. The ovarian tumors were diagnosed in 47% of the cases following investigation of patients' symptoms. In 41%, diagnosis was made as a consequence of check-up exams performed during the routine follow-up of BrC survivors. Patients with PPMBr were more likely to present with FIGO ovarian stage III-IV, compared to women with solitary OvC (73% vs 60. 3%, P < 0.05), and less likely to have borderline tumors (3.4% vs 17. 9%, P = 0.007). Family history of OvC/BrC was recorded in 26% of this group of patients compared to 10.5% among patients with solitary OvC (P = 0.003). Patients with PPMBr had an exceptionally high prevalence of BRCA1-2 mutations (57%), irrespective of family history. CONCLUSIONS: Patients with PPMBr present with more advanced disease and invasive-type epithelial ovarian tumors when compared to cases associated with solitary OvC. The rate of BRCA1-2 mutations in Jewish women with OvC who had PPMBr is at least twice as high as in Jewish women with OvC as the solitary disease.

Selected risk factors for transitional cell bladder cancer.

Cancer of the bladder has long been associated with environmental risk factors, such as occupational hazards and smoking. The aim of the current study was to evaluate the contribution of known risk factors on a community basis in the 1990s, in view of the recent worldwide efforts to control environmental hazards. The study population included 140 male patients and 280 matched controls. Information on demographic data, occupational exposure, smoking habits and disease history was obtained by personal interviews. Our study confirmed the role of industrial occupation (OR=2.21; 95% Cl=1. 21-4.02) and exposure to 3 or more metals (OR=3.65; 95% Cl=1.21-11. 08) as risk factors. Prostate enlargement was also found significant, but probably not causal (OR=2.23; 95% Cl=1.29-3.87). Surprisingly, smoking showed only an inconsistent association with higher rates among those who started to smoke before 18 years of age (OR=2.64; 95% Cl=1.4-4.99) and those who smoked more than 30 cigarettes per day (OR=1.82; 95% Cl=0.95-3.49). The above data suggest that current efforts to reduce the load of bladder cancer in the population, via environmental measures, have not as yet yielded significant effects.