Characteristics relating to ovarian cancer risk: collaborative analysis of seven U.S. case-control studies. Epithelial ovarian cancer in black women. Collaborative Ovarian Cancer Group.

BACKGROUND: Previous epidemiologic studies of ovarian cancer have focused chiefly on White women, who have a higher incidence of ovarian cancer than Black women. No study has previously examined risk factors for ovarian cancer among Black women. PURPOSE: This study was designed to evaluate the risk of epithelial ovarian cancer in Black women in relation to reproductive characteristics such as pregnancy, oral contraceptive use, and breast-feeding, and to determine whether differences in reproductive factors between Black and White women account for differences in ovarian cancer incidence. METHODS: Combining interview data from seven case-control studies, we compared reproductive characteristics of 110 Black case subjects with a diagnosis of epithelial ovarian cancer between 1971 and 1986 with characteristics of 251 Black population control subjects and 114 Black hospital control subjects. We also compared the prevalence of reproductive factors in 246 Black population control subjects and 4378 White population control subjects and estimated the fraction of Black-White differences in ovarian cancer incidence attributable to racial differences in prevalence of these characteristics. RESULTS: Decreased risks of epithelial ovarian cancer in Black women were associated with parity of four or higher (odds ratio [OR] = 0.53; 95% confidence interval [CI] = 0.25-1.1), breast-feeding for 6 months or longer (OR = 0.85; 95% CI = 0.36-2.0), and use of oral contraceptives for 6 years or longer (OR = 0.62; 95% CI = 0.24-1.6). A greater proportion of Black women (48%) than White women (27%) reported four or more term pregnancies, and Black women (62%) were more likely than White women (53%) to have breast-fed their children. Oral contraceptive use was more common among White women (59%) than Black women (51%). CONCLUSION: Differences in the prevalence of other factors related to ovarian cancer risk or differences in genetic susceptibility must explain most of the Black-White differences in incidence of ovarian cancer.

Rates and risks of ovarian cancer in subgroups of white women in the United States. The Collaborative Ovarian Cancer Group.

OBJECTIVE: To provide estimates of the age-adjusted incidence and lifetime risk of ovarian cancer in subgroups of women defined by key risk factors. METHODS: We combined data from seven case-control studies (1122 cases and 5359 controls) with Surveillance, Epidemiology, and End Results incidence data to estimate the incidence rate and probability of developing ovarian cancer within subgroups of women defined according to the three major known risk factors: a history of ovarian cancer in the mother or sister, years of oral contraceptive (OC) use, and number of term pregnancies. RESULTS: Among women with no family history of ovarian cancer, the risk at age 65 varied from 0.3% among those who had had three or more term pregnancies and 4 or more years of OC use, to 1.6% among nulliparous women with no OC use. Among women with a positive family history, the risk of developing ovarian cancer by age 65 was estimated as 4.4% and the lifetime risk as 9.4%. The data were too sparse to estimate the risks associated with OC use and pregnancy among women with a positive family history. CONCLUSIONS: The risk of developing ovarian cancer within the total population of white women can be divided informatively into component risks within subpopulations. At birth, the estimated risk of developing ovarian cancer before age 65 for the total population is 0.8%, but the component risks vary 15-fold, from 0.3 to 4.4%.

Prevalence and contribution of BRCA1 mutations in breast cancer and ovarian cancer: results from three U.S. population-based case-control studies of ovarian cancer.

We investigate the familial risks of cancers of the breast and ovary, using data pooled from three population-based case-control studies of ovarian cancer that were conducted in the United States. We base estimates of the frequency of mutations of BRCA1 (and possibly other genes) on the reported occurrence of breast cancer and ovarian cancer in the mothers and sisters of 922 women with incident ovarian cancer (cases) and in 922 women with no history of ovarian cancer (controls). Segregation analysis and goodness-of-fit testing of genetic models suggest that rare mutations (frequency .0014; 95% confidence interval .0002-.011) account for all the observed aggregation of breast cancer and ovarian cancer in these families. The estimated risk of breast cancer by age 80 years is 73.5% in mutation carriers and 6.8% in noncarriers. The corresponding estimates for ovarian cancer are 27.8% in carriers and 1.8% in noncarriers. For cancer risk in carriers, these estimates are lower than those obtained from families selected for high cancer prevalence. The estimated proportion of all U.S. cancer diagnoses, by age 80 years, that are due to germ-line BRCA1 mutations is 3.0% for breast cancer and 4.4% for ovarian cancer. Aggregation of breast cancer and ovarian cancer was less evident in the families of 169 cases with borderline ovarian cancers than in the families of cases with invasive cancers. Familial aggregation did not differ by the ethnicity of the probands, although the number of non-White and Hispanic cases (N = 99) was sparse.

Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies. I. Methods. Collaborative Ovarian Cancer Group.

Data from 12 US case-control studies of ovarian cancer, conducted during the period 1956-1986 and representing some 3,000 cases and 10,000 controls, were pooled and reanalyzed. Separate analyses were conducted for four subgroups of the pooled data: invasive epithelial ovarian cancers in white women; epithelial ovarian cancers of low malignant potential in white women, epithelial ovarian cancers in black women, and nonepithelial ovarian cancers. This paper gives a brief description of the participating studies and describes the methods used in the collaborative analysis.

Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies. II. Invasive epithelial ovarian cancers in white women. Collaborative Ovarian Cancer Group.

Data collected from 2,197 white ovarian cancer patients and 8,893 white controls in 12 US case-control studies conducted in the period 1956-1986 were used to evaluate the relation of invasive epithelial ovarian cancer to reproductive and menstrual characteristics, exogenous estrogen use, and prior pelvic surgeries. Clear trends of decreasing risk were evident with increasing number of pregnancies (regardless of outcome) and increasing duration of breast feeding and oral contraceptive use. Ovarian dysfunction leading to both infertility and malignancy is an unlikely explanation for these trends for several reasons: 1) The trends were evident even among the highly parous; 2) risk among nulliparous women did not vary by marital status or gravidity; and 3) risk among ever-married women showed little relation to length of longest pregnancy attempt or history of clinically diagnosed infertility. Risk was increased among women who had used fertility drugs and among women with long total duration of premenopausal sexual activity without birth control; these associations were particularly strong among the nulligravid. No consistent trends in risk were seen with age at menarche, age at menopause, or duration of estrogen replacement therapy. A history of tubal ligation or of hysterectomy with ovarian conservation was associated with reduced ovarian cancer risk. These observations suggest that pregnancy, breast feeding, and oral contraceptive use induce biological changes that protect against ovarian malignancy, that, at most, a small fraction of the excess ovarian cancer risk among nulliparous women is due to infertility, and that any increased risk associated with infertility may be due to the use of fertility drugs.

Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies. III. Epithelial tumors of low malignant potential in white women. Collaborative Ovarian Cancer Group.

Epithelial ovarian neoplasms of low malignant potential, also called borderline ovarian tumors, have various features of malignancy, but they do not invade the ovarian stroma. Women with these tumors usually are younger when diagnosed and have better prognoses than do women with invasive tumors. There have been few epidemiologic studies of borderline tumors, and it is unclear whether there are etiologic differences between the two types of tumor behavior. Combined data from nine case-control studies, conducted from 1974 to 1986 and representing 327 white women with tumors of low malignant potential and 4,144 white controls, were used to evaluate the relation between these tumors and personal characteristics related to invasive ovarian cancer. The risk profile for tumors of low malignant potential was found to be similar to that for invasive tumors, with two exceptions: Compared with that of invasive tumors, risk of borderline tumors was less clearly reduced among women who had used oral contraceptives and more clearly elevated among women with a history of infertility.

Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies. IV. The pathogenesis of epithelial ovarian cancer. Collaborative Ovarian Cancer Group.

Two hypotheses have been proposed to explain the reduced risk of epithelial ovarian cancer associated with pregnancy and oral contraceptive use. The first states that some sequelae of ovulation increase the likelihood of malignancy and that pregnancies and oral contraceptives protect by suppressing ovulation. The second hypothesis states that circulating levels of pituitary gonadotropins increase the risk of malignancy and that pregnancies and oral contraceptives protect by suppressing secretion of these hormones. The authors evaluate the two hypotheses in light of combined data from 12 United States case-control studies of epithelial ovarian cancer in white women conducted from 1956 to 1986. While a number of observations support both hypotheses, there are exceptions. Differential risk reduction associated with pregnancy and oral contraceptive use (pregnancy being the more effective in young women and the less effective in older women) conflicts with the first "ovulation" hypothesis, while reduced risk associated with breast feeding and absence of altered risk associated with estrogen replacement therapy conflicts with the second "gonadotropin" hypothesis. Several findings would not have been predicted by either hypothesis, e.g., only weak trends relate cancer risk to age at menarche, and, among older women, no clear trends relate risk to age at menopause. Odds ratio attenuation due to errors in reporting personal characteristics may be responsible for some of these inconsistencies. Multidisciplinary research is needed to clarify the etiologic roles of ovulation and gonadotropin stimulation, both of which may enhance carcinogenesis in the ovarian epithelium.

Characteristics relating to ovarian cancer risk: collaborative analysis of 12 U.S. case-control studies. VI. Nonepithelial cancers among adults. Collaborative Ovarian Cancer Group.

Nonepithelial ovarian cancers are rare, and little is known about their etiology. Of particular interest are the effects of oral contraceptive use and pregnancy, both of which are associated with large decreases in risk for epithelial ovarian cancer. We examined the risk factors for nonepithelial ovarian tumors by combining data from four case-control studies conducted in the United States. We compared personal characteristics of 38 germ cell cases and 45 stromal cases, respectively, with 1,142 and 2,617 general population controls. All subjects were over age 18 years. For germ cell tumors, there was a weak negative association with parity but no consistent pattern of decreasing risk with increasing parity. In contrast, relative to nulligravid women, gravid nulliparous women were at increased risk of developing a germ cell cancer [odds ratio (OR) = 4.8, 95% confidence interval (CI) = 1.2-18.6]. The use of oral contraceptives was also associated with elevated risk (OR = 2.0, 95% CI = 0.77-5.1); however, no clear trends in risk were observed. For stromal tumors, oral contraceptive use was associated with decreased risk (OR = 0.37, 95% CI = 0.16-0.83), whereas pregnancy was associated with a small elevation in risk. A trend of increasing risk with increasing age at first term pregnancy was observed, with an odds ratio of 3.6 (95% CI = 1.0-12.5) for a first birth after age 29 years. Risk factors for nonepithelial ovarian cancers do not appear to parallel each other or those for epithelial ovarian cancer.

Risks of cancer among members of families in the Gilda Radner Familial Ovarian Cancer Registry.

BACKGROUND: Increasing scientific and public interest in hereditary cancer syndromes has created a need for estimates of lifetime cancer risks among members of families with such syndromes. METHODS: Data from the Gilda Radner Familial Ovarian Cancer Registry were used to evaluate risk for cancers of the breast, cervix, uterus, colorectum, and prostate in members of 143 families containing three or more reported cases of ovarian cancer among first- or second-degree relatives. These risks were compared with those that were expected based on general population rates obtained from the Connecticut Tumor Registry. RESULTS: Overall, family members' risk of cancer at any nonovarian site was 1.5 times that of the general population (P < 0.001). Among female members, risk for cancer of the breast was 2.5 times that of the general population. Risk for cancer of the uterus was 5 times that of the general population and increased with increasing number of first-degree relatives with ovarian cancer. Among male family members having three or more first-degree relatives with ovarian cancer, prostate cancer risk was 4.5 times that of the general population. No excess risks were observed for cancer of the colorectum. CONCLUSIONS: These data support previous reports of coaggregation of cancer of the breast, uterus and ovary, and suggest coaggregation between cancer of the ovary and prostate. Differences in cancer risk profiles observed in these families with multiple ovarian cancer and in carriers of the gene BRCA1 suggest that hereditary ovarian cancer is genetically heterogeneous.