National Cancer Institute®
Last Modified: October 1, 2002
UI - 11027080
AU - Sanderson M; Williams MA; Weiss NS; Hendrix NW; Chauhan SP
TI - Oral contraceptives and epithelial ovarian cancer. Does dose matter?
SO - J Reprod Med 2000 Sep;45(9):720-6
AD - Department of Epidemiology and Biostatistics, University of South Carolina, Columbia 29208, USA. email@example.com
OBJECTIVE: To determine the risk of ovarian cancer among women who use low-estrogen-dose oral contraceptives. STUDY DESIGN: The study used data on white women under 70 years of age who had been enrolled in a population-based case-control study conducted between 1986 and 1988 in three western Washington counties. Women with ovarian cancer (n = 276) were ascertained through a population-based cancer registry, and controls (n = 391) were selected by random digit dialing. Unconditional logistic regression was used to estimate the risk of ovarian cancer associated with oral contraceptive use. RESULTS: After adjustment for age and parity, women who took oral contraceptives for at least three months were at decreased risk of ovarian cancer (odds ratio [OR] 0.8, 95% confidence interval [CI] 0.5-1.1) relative to women who never used this form of contraception. The reduced risk of ovarian cancer was present among women whose only preparation contained a low (< 50 micrograms ethinyl estradiol or < 80 micrograms mestranol) (OR 0.6, 95% CI 0.3-1.1) and high (OR 0.8, 95% CI 0.5-1.2) estrogen dose. CONCLUSION: While our results are limited in their statistical precision and by the inability of many subjects to recall the brands of oral contraceptives that they took, they suggest that the newer, low-estrogen-dose oral contraceptives confer a benefit regarding ovarian cancer risk similar to that conferred by earlier, high-estrogen-dose formulations.
UI - 11962261
AU - Fleischauer AT; Olson SH; Mignone L; Simonsen N; Caputo TA; Harlap S
TI - Dietary antioxidants, supplements, and risk of epithelial ovarian cancer.
SO - Nutr Cancer 2001;40(2):92-8
AD - Dept. of Epidemiology, CB 7435, School of Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.
Several studies of dietary and serum antioxidant micronutrients (vitamins A, C, and E and beta-carotene) suggest that higher levels may be protective for ovarian cancer. None of these has examined supplements. We used a food frequency questionnaire and additional questions on supplements to study 168 histologically confirmed epithelial ovarian cancer cases, 159 community controls, and 92 hospital-based controls. Antioxidant consumption from diet or supplements was calculated in milligrams or international units per day. In multivariate analyses using only community controls, the highest levels of intake of vitamins C and E from supplements were protective: odds ratio (OR) = 0.40 [95% confidence interval (CI) = 0.21-0.78] and OR = 0.33 (95% CI = 0.18-0.60), respectively. Consumption of antioxidants from diet was unrelated to risk. In analyses combining antioxidant intake from diet and supplements, vitamins C (> 363 mg/day) and E (> 75 mg/day) were associated with reduced risks: OR = 0.45 (95% CI = 0.22-0.91) and OR = 0.44 (95% CI = 0.21-0.94), respectively. Results were similar, with some attenuation toward the null, in analyses combining both control groups. The levels of vitamins C and E associated with the protective effect were well above the current US Recommended Dietary Allowances. These findings support the hypothesis that antioxidant vitamins C and E from supplements are related to a reduced risk of ovarian cancer.
UI - 12172980
AU - Minko T; Paranjpe PV; Qiu B; Lalloo A; Won R; Stein S; Sinko PJ
TI - Enhancing the anticancer efficacy of camptothecin using biotinylated poly(ethylene glycol) conjugates in sensitive and multidrug-resistant human ovarian carcinoma cells.
SO - Cancer Chemother Pharmacol 2002 Aug;50(2):143-50
AD - Center for Biomaterials, 610 Taylor Road, Piscataway, NJ 08854, USA.
BACKGROUND: Camptothecin (CPT) is an anticancer agent that kills cells by converting DNA topoisomerase I into a DNA-damaging agent. Although CPT and its derivatives are now being used to treat tumors in a variety of clinical protocols, the low water solubility of the drug and its unique pharmacodynamics and reactivity in vivo limit its delivery to cancer cells. To increase the anticancer efficacy of CPT a special drug delivery system is needed. PURPOSE: To synthesize a novel camptothecin-poly(ethylene glycol) conjugate (CPT-PEG) which includes biotin as a moiety to enhance nonspecific and/or targeted uptake via the sodium-dependent multivitamin transporter (SMVT) and to evaluate its anticancer activity and apoptosis induction. METHODS: CPT-PEG and CPT-PEG-biotin conjugates were synthesized and studied in vitro in A2780 sensitive and A2780/AD multidrug-resistant human ovarian carcinoma cells. Cytotoxicity, apoptosis induction, expression of genes encoding BCL-2 and apoptotic protease-activating factor 1 (APAF-1) proteins and caspases 3 and 9 as well as caspase activity were measured.RESULTS. We found that the conjugation of CPT with a simple linear PEG polymer led to a more than 12-fold enhancement of CPT toxicity in both sensitive and multidrug-resistant cells. Biotinylation of the PEG led to a further increase in CPT toxicity (5.2 times in sensitive and 2.1 times in multidrug-resistant cells) compared to the nonbiotinylated CPT-PEG conjugate. As a result, the cytotoxicity of the CPT-PEG-biotin conjugate increased more than 60 times in sensitive and almost 30 times in resistant cells, probably by enhancing nonspecific passive and/or SMVT-mediated uptake. In contrast, the same amounts of PEG and PEG-biotin conjugates without CPT did not induce cell death in either sensitive or resistant cells. Further analysis showed that the biotinylated CPT-PEG conjugate induced apoptosis more significantly than the same equivalent concentrations of free CPT or nonbiotinylated CPT-PEG. The enhancement of proapoptotic activity was achieved by the overexpression of genes encoding the APAF-1, and caspases 3 and 9, increasing caspase activity and simultaneously downregulating the BCL-2 gene. CONCLUSIONS: The results obtained demonstrate that the binding of CPT to PEG/PEG-biotin polymers increases its cytotoxicity, ability to induce apoptosis by the activation of caspase-dependent cell death signaling pathway and simultaneous suppression of antiapoptotic cellular defense. This suggests that the targeting approach utilizing transporters such as SMVT may substantially improve the delivery of CPT and its anticancer activity by enhancing cellular permeability and possibly retention of CPT.
UI - 12240546
AU - Thames HD; Petersen C; Petersen S; Nieder C; Baumann M
TI - Immunohistochemically detected p53 mutations in epithelial tumors and results of treatment with chemotherapy and radiotherapy. A treatment-specific overview of the clinical data.
SO - Strahlenther Onkol 2002 Aug;178(8):411-21
AD - Department of Biomathematics, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
BACKGROUND: The aim was to ascertain whether many hundreds of clinical reports over the last decade are consistent with the prediction of a poorer outcome in cancer patients with p53 abnormalities treated with cytotoxic drugs and radiation. MATERIAL AND METHOD: There are 301 studies on the influence of p53 overexpression published through summer 2000, in which chemotherapy or radiotherapy was used alone or in combination with surgery. From 45 reports meeting stringent selection rules, comparison groups are identified in whom the same measure of outcome was reported for the same treatment applied to the same tumor, with results corrected for important prognostic factors. Metaanalysis techniques are then applied to the comparison groups. Attention was limited to reports using immunohistochemical techniques, to form comparison groups of sufficient size. RESULTS: Four comparison groups were identified by treatment and endpoint: 1) Stage I-III breast cancer (surgery and chemotherapy, disease-free survival, seven studies); 2) stage I-III breast cancer (surgery and chemotherapy, overall survival, six studies); 3) stage II-IV head and neck cancer (radiotherapy and chemotherapy, overall survival, five studies); 4) FIGO I-IV ovarian cancer (surgery and chemotherapy, overall survival, six studies). In the breast (disease-free survival) and ovarian (overall survival) comparison groups, the hazard ratio for a deleterious effect of p53 overexpression was significant or marginally significant, depending on assumed ranges for unreported hazard ratios in non-significant studies. CONCLUSIONS: Despite the many caveats related to metaanalysis applied to retrospective data, high variability of immunohistochemical technique, etc., a nearly significant negative effect of p53 overexpression on outcome of treatment with cytotoxic drugs and radiation emerges in the few studies where heterogeneity can be sufficiently reduced or accounted for.
UI - 12237282
AU - Brose MS; Rebbeck TR; Calzone KA; Stopfer JE; Nathanson KL; Weber BL
TI - Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program.
SO - J Natl Cancer Inst 2002 Sep 18;94(18):1365-72
AD - Department of Medicine and Abramson Family Cancer Research Institute, University of Pennsylvania Cancer Center, Philadelphia 19104, USA.
BACKGROUND: Increasing numbers of BRCA1 mutation carriers are being identified in cancer risk evaluation programs. However, no estimates of cancer risk specific to a clinic-based population of mutation carriers are available. These data are clinically relevant, because estimates based on families ascertained for linkage studies may overestimate cancer risk in mutation carriers, and population-based series may underestimate it. Wide variation in risk estimates from these disparate ascertainment groups makes counseling in risk evaluation programs difficult. The purpose of this study was to estimate BRCA1-related cancer risks for individuals ascertained in a breast cancer risk evaluation clinic. METHODS: Cumulative observed and age-adjusted cancer risk estimates were determined by analyzing 483 BRCA1 mutation carriers in 147 families identified in two academic breast and ovarian cancer risk evaluation clinics. Cancer risks were computed from the proportion of individuals diagnosed with cancer during a 10-year age interval from among the total number of individuals alive and cancer-free at the beginning of that interval. Age-of-diagnosis comparisons were made using two-sided Student's t tests. RESULTS: By age 70, female breast cancer risk was 72.8% (95% confidence interval [CI] = 67.9% to 77.7%) and ovarian cancer risk was 40.7% (95% CI = 35.7% to 45.6%). The risk for a second primary breast cancer by age 70 was 40.5% (95% CI = 34.1% to 47.0%). We also identified an increased risk of cancer of the colon (twofold), pancreas (threefold), stomach (fourfold), and fallopian tube (120-fold) in BRCA1 mutation carriers as compared with Surveillance, Epidemiology, and End Results (SEER) Program population-based estimates. CONCLUSION: The estimates for breast and ovarian cancer risk in BRCA1 mutation carriers is higher than population-based estimates but lower than estimates based on families ascertained for linkage studies. These cancer risk estimates may most closely approximate those faced by BRCA1 mutation carriers identified in risk evaluation clinics.
UI - 12237285
AU - Hilton JL; Geisler JP; Rathe JA; Hattermann-Zogg MA; DeYoung B; Buller
TI - RE Inactivation of BRCA1 and BRCA2 in ovarian cancer.
SO - J Natl Cancer Inst 2002 Sep 18;94(18):1396-406
AD - Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Holden Comprehensive Cancer Center, Iowa City, IA, USA.
BACKGROUND: Although BRCA1 and BRCA2 play important roles in hereditary ovarian cancers, the extent of their role in sporadic ovarian cancers and their mechanisms of inactivation are not yet well understood. Our goal was to characterize BRCA2 mutations and mRNA expression in a group of ovarian tumors previously evaluated for BRCA1 mutations and mRNA expression. METHODS: The tumors of 92 unrelated women with "ovarian" cancer (i.e., ovarian, peritoneal, or fallopian tube cancer) were screened for BRCA2 null mutations using a protein truncation test. Methylation-specific polymerase chain reaction (PCR) was used to examine the BRCA2 promoter for hypermethylation in tumors that did not express BRCA2 mRNA. All statistical tests were two-sided. RESULTS: Nine tumors had a germline (n = 5) or somatic (n = 4) BRCA2 mutation; each was associated with loss of heterozygosity. All of the somatic (1445delC, E880X, 4286del8, and 5783delT) and one of the germline (5984ins4) mutations were unique to this study. One tumor had somatic mutations in both BRCA1 and BRCA2. Two tumors are, to our knowledge, the first cases of germline BRCA2-associated peritoneal cancer. Twelve additional tumors lacked detectable BRCA2 mRNA, but the BRCA2 promoter was hypermethylated in only one of them, suggesting that other mechanisms effect transcriptional silencing of BRCA2. Tumors lacking BRCA1 mRNA were more likely to lack BRCA2 mRNA than tumors expressing BRCA1 mRNA (P<.001). Overall, 82% (95% confidence interval [CI] = 74% to 90%) of the tumors contained alterations in BRCA1, BRCA2, or both genes. Of 41 informative tumors with some alteration in BRCA2, 36 also had an alteration in BRCA1. The frequency, but not the mechanism, of BRCA1 or BRCA2 dysfunction in ovarian cancer was independent of family history. CONCLUSIONS: Multiple mechanisms cause nearly universal dysfunction of BRCA1 and/or BRCA2 in hereditary and sporadic ovarian carcinoma. Ovarian cancers with BRCA2 dysfunction often have simultaneous BRCA1 dysfunction.
UI - 2348208
AU - Gwinn ML; Lee NC; Rhodes PH; Layde PM; Rubin GL
TI - Pregnancy, breast feeding, and oral contraceptives and the risk of epithelial ovarian cancer.
SO - J Clin Epidemiol 1990;43(6):559-68
AD - Division of Reproductive Health, Centers for Disease Control, Atlanta, GA 30333.
To quantify the effects of cumulative months of pregnancy, breast feeding, and oral contraceptive use on the risk of developing epithelial ovarian cancer, the authors used data collected for the Cancer and Steroid Hormone Study--a multicenter, population-based, case-control study. Detailed reproductive histories were obtained from 436 women aged 20-54 with epithelial ovarian cancer newly diagnosed between December random from the same geographic areas. Estimated relative risks of epithelial ovarian cancer were 0.6 (95% confidence interval (CI) 0.5-0.8) for women who had ever been pregnant, 0.6 (95% CI 0.5-0.8) for women who had ever breast fed, and 0.5 (95% CI 0.5-0.7) for women who had ever used oral contraceptives. Logistic regression analysis revealed a strong trend in decreasing risk of epithelial ovarian cancer with increasing cumulative months of pregnancy; this effect was less pronounced in women aged 50-54 than in younger women. In contrast, a marked reduction in risk was associated with ever having breast fed or used oral contraceptives, while the decrease in risk from additional months of either of these exposures was less than that for pregnancy.
UI - 1868732
AU - Stanford JL
TI - Oral contraceptives and neoplasia of the ovary.
SO - Contraception 1991 Jun;43(6):543-56
AD - Fred Hutchinson Cancer Research Center, Program in Epidemiology (MP-474) Seattle, Washington 98104.
Epidemiologic literature on oral contraceptives in relation to primary ovarian cancer is reviewed. Compared to women who have never used oral contraceptives, women who have ever taken oral contraceptives have about a 30% reduction in risk for epithelial ovarian cancer, and five or more years of use is associated with a 50% reduction in risk. The protective effect of oral contraceptives persists for ten or more years after use is discontinued, and becomes apparent several years after beginning use. Effects of oral contraceptives are similar for malignant and borderline malignant epithelial ovarian cancer. Reduced risks among oral contraceptive users have been observed for all major histologic subtypes of epithelial ovarian cancer, and for women from developed and developing countries. Risk estimates for epithelial ovarian cancer in relation to oral contraceptive use stratified by age at diagnosis or parity are not uniform across studies. No consistent protective effect is apparent for non-epithelial ovarian tumors or benign ovarian tumors, including teratomas and cystadenomas, although limited data are available on the relationship between oral contraceptives and these neoplasms. Several areas for future research are described.
UI - 1874572
AU - Franceschi S; Parazzini F; Negri E; Booth M; La Vecchia C; Beral V;
TI - Tzonou A; Trichopoulos D Pooled analysis of 3 European case-control studies of epithelial ovarian cancer: III. Oral contraceptive use.
SO - Int J Cancer 1991 Aug 19;49(1):61-5
AD - Epidemiology Unit, Aviano Cancer Center, Italy.
The relationship between use of oral contraceptives (OCs) and other contraceptive methods and the risk of ovarian cancer was examined in a combined analysis of 3 hospital-based case-control studies conducted in Italy, the United Kingdom, and Greece, for a total of 971 ovarian cancer cases and 2,258 controls under age 65. Compared with never-users, the combined multivariate relative risk (RR) for ever-users was 0.6 (95% confidence interval, CI = 0.4-0.8) and the estimates were consistent in the 3 datasets. The protection was also similar across strata of age and parity. Considering various measures of OC use, available in the Italian and British datasets only, the protection conveyed on ovarian cancer risk increased with the duration of use and persisted in the medium-long period: the RR in women reporting their last OC use greater than or equal to 15 years prior to diagnosis was 0.5 (95% CI = 0.2-1.0). The risks in ever-users were appreciably lower in those women who reported their first OC use before 25 years of age (RR = 0.3 for first use before age 25, 0.8 for first use at age 25-34 and 0.7 at 35 years or after). Such findings emerged similarly from Italian and British data. This combined analysis, besides offering further quantitative estimates of the protective effects of OCs on ovarian cancer risk in European populations, provides useful insights into the time pattern of the relationship between OC use and ovarian carcinogenesis, suggesting that the protection persists for 15 years or more after cessation of use and may be larger for use at younger age.
UI - 1877597
AU - Irwin KL; Weiss NS; Lee NC; Peterson HB
TI - Tubal sterilization, hysterectomy, and the subsequent occurrence of epithelial ovarian cancer.
SO - Am J Epidemiol 1991 Aug 15;134(4):362-9
AD - Centers for Disease Control, Atlanta, GA.
Several hypotheses predict that tubal sterilization and hysterectomy may influence a woman's risk of developing ovarian cancer. To examine the relation between these surgeries and epithelial ovarian cancer, the authors analyzed data from the Cancer and Steroid Hormone Study, a case-control study of women aged 20-54 years. Eight population-based cancer registries in the United States identified women with newly diagnosed epithelial ovarian cancer during 1980-1982 (n = 494). A comparison sample of female residents of these eight areas (n = 4,238) was identified through random digit dialing. Women who had had tubal sterilization (relative risk (RR) = 0.69, 95% confidence interval (Cl) 0.50-0.95), a hysterectomy only (RR = 0.55, 95% Cl 0.38-0.81), or a hysterectomy with unilateral oophorectomy (RR = 0.60, 95% Cl 0.31-1.17) had lower risks of ovarian cancer than did women who had never had any sterilization surgery. However, the negative associations with tubal sterilization and hysterectomy only appeared to wane after two decades. These findings may be partly explained by the screening for occult ovarian pathology that often accompanies pelvic surgery: Women whose ovaries screen as "negative" may be temporarily at low risk of being diagnosed with ovarian cancer. However, because the decreased risks persisted for so long, it is conceivable that hormonal, mechanical, or circulatory sequelae of these sterilization procedures may act to lower ovarian cancer risk.
UI - 1897499
AU - Harlow BL; Cramer DW; Geller J; Willett WC; Bell DA; Welch WR
TI - The influence of lactose consumption on the association of oral contraceptive use and ovarian cancer risk.
SO - Am J Epidemiol 1991 Sep 1;134(5):445-53
AD - Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
The authors investigated the joint effects of diet and oral contraceptive use on ovarian cancer risk in 194 white women aged 65 years or less with epithelial ovarian cancer and 193 age- and residence-matched controls in Boston between 1984 and 1987 by using in-person interviews and self-administered food frequency questionnaires. Use of oral contraceptives for 3 months or more was associated with a modest protective effect for ovarian cancer (odds ratio (OR) = 0.7, 95 percent confidence interval (CI) 0.5-1.1). In women who consumed 11 g or less per day of lactose, use of oral contraceptives for 3 months or more was associated with a nonsignificant increased risk (OR = 1.6, 95 percent CI 0.8-3.2). In women who consumed more than 11 g per day of lactose, use of oral contraceptives for 3 months or more was associated with a substantially decreased risk of ovarian cancer (OR = 0.3, 95 percent CI 0.1-0.7). Within this group, the strongest association occurred with more than 4 years of total oral contraceptive use (OR = 0.2, 95 percent CI 0.1-0.6) and in those who had more than 2 years of oral contraceptive use after age 30 years (OR = 0.1, 95 percent CI 0.03-0.4). These results suggest that, with respect to ovarian cancer, lactose users may be the most likely to benefit from oral contraceptive use and that the benefit may be strongest when oral contraceptive use occurs after age 30 years.
UI - 1800425
AU - Parazzini F; Restelli C; La Vecchia C; Negri E; Chiari S; Maggi R;
TI - Mangioni C Risk factors for epithelial ovarian tumours of borderline malignancy.
SO - Int J Epidemiol 1991 Dec;20(4):871-7
AD - Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
A case-control study was conducted on 91 cases with histologically-confirmed borderline ovarian tumours and 237 control subjects in hospital for acute non-gynaecological, hormonal or neoplastic disease. Women reporting three or more births, compared to nulliparae, had a relative risk (RR) estimate of 0.6, but this finding was not statistically significant (95% confidence interval (CI): 0.2-1.4). The risk of borderline tumours increased, although not significantly, with later age at first birth: compared to women reporting first birth at age 24 or before, the RRs were 1.3 and 1.7 in those reporting respectively their first birth at age 25-29 and 30 years or more. No significant relationship emerged between borderline ovarian cancer and age at menarche, menopausal status and lifelong menstrual pattern. Cases tended to report a later age at menopause than controls, but the trend in risk was not statistically significant. Nine cases (9.9%) and 68 controls (24.9%) reported oral contraceptive use: compared with never users the multivariate RR for ever users was 0.3, and the risk dropped with duration of use to 0.2 in users for two years or more (chi 2 (1) trend = 12.70, p less than 0.001). This study provides epidemiological evidence of a pathogenetic continuum between borderline and invasive ovarian tumours.
UI - 1544753
AU - Chen Y; Wu PC; Lang JH; Ge WJ; Hartge P; Brinton LA
TI - Risk factors for epithelial ovarian cancer in Beijing, China.
SO - Int J Epidemiol 1992 Feb;21(1):23-9
AD - Department of Obstetrics and Gynaecology, Peking Union Medical College, Beijing, China.
A study in Beijing, China of 112 pathologically confirmed epithelial ovarian cancer cases and 224 age-matched community controls enabled evaluation of risk in relation to reproductive, medical, familial, and selected lifestyle factors. An inverse relationship was observed between the number of full-term pregnancies and ovarian cancer risk. Compared to nulliparous women, subjects with one, two, or three full-term pregnancies were at 50%, 70%, or 90% reduced risks, respectively (P for trend less than 0.01). A positive correlation was found between the number of ovulatory years and risk, with a 2.6-fold increased risk for women with 30 or more compared to less than 10 ovulatory years (P for trend less than 0.01). Infertility, as estimated in various ways, was also found to be an important risk factor. When parity was taken into account, age at first pregnancy was not related to ovarian cancer risk. No protective effect was associated with mumps virus infection. In contrast, risk increased significantly as serum mumps virus antibody titres increased (P for trend less than 0.01). An elevated risk was found in women with a history of long-term (greater than 3 months) application of talc-containing dusting powder to the lower abdomen and perineum (Relative risk 3.9, 95% confidence interval: 0.9-10.63). These findings suggest that Chinese women have risk factors similar to those of occidental women.
UI - 1559340
AU - Petitti DB; Porterfield D
TI - Worldwide variations in the lifetime probability of reproductive cancer in women: implications of best-case, worst-case, and likely-case assumptions about the effect of oral contraceptive use.
SO - Contraception 1992 Feb;45(2):93-104
AD - Department of Family and Community Medicine, University of California, San Francisco School of Medicine 94143.
Cancer incidence in countries representative of three patterns of reproductive cancer and age-specific mortality was used to estimate the effect of oral contraceptive use on the lifetime probability of reproductive cancer under three sets of assumptions about the effects of oral contraceptives. Under the set of assumptions considered likely, oral contraceptives were estimated to reduce or increase only slightly the lifetime probability of any reproductive cancer in each setting. Under worst-case assumptions, oral contraceptives were estimated to increase the lifetime probability of reproductive cancer only modestly in settings with low cancer rates and in settings with high rates of breast, ovarian, and endometrial cancer, but it might have a large impact on lifetime probability of reproductive cancer in settings with high cervical cancer rates. Under best-case assumptions, oral contraceptives were estimated to decrease the lifetime probability of reproductive cancer in each setting; this reduction was estimated to be greatest in settings where endometrial and ovarian cancer incidence are high.
UI - 1622631
AU - Spicer DV; Pike MC
TI - The prevention of breast cancer through reduced ovarian steroid exposure.
SO - Acta Oncol 1992;31(2):167-74
AD - University of Southern California School of Medicine, Department of Preventive Medicine, Los Angeles 90033-9987.
Analysis of epidemiologic data on cancers of the breast, ovary and endometrium; the effects of endogenous hormones on cell proliferation; and current carcinogenesis concepts, suggest that hormonal contraceptives can be developed that will reduce lifetime risk of all 3 cancers. The 'unopposed-estrogen hypothesis' accounts for endometrial cancer risk factors. Ovarian cancer risk is closely related to the total frequency of ovulation. The risk of breast cancer can be explained by an 'estrogen-plus-progestogen hypothesis'. On the basis of this analysis an hormonal contraceptive regimen has been developed consisting of a gonadotropin-releasing hormone agonist (GnRHA) plus continuous low-dose add-back estrogen and a short course of progestogen every fourth month. The total dose of add-back estrogen is estimated to be approximately 38% that in present-day low-dose combination-type oral contraceptives (COCs). The total dose of progestogen is approximately 15% that in COCs. This regimen prevents ovulation and should thus reduce ovarian cancer risk. It also reduces the exposure of the endometrium to unopposed estrogen, and the exposure of the breast to estrogen-plus-progestogen. It is estimated that use of such a regimen for 10 years will only reduce lifetime risk of endometrial cancer by one-sixth, but lifetime risk of ovarian cancer is estimated to be reduced by two-thirds, and lifetime risk of breast cancer is estimated to be reduced by one-half.
UI - 1294683
AU - Badawy YA; Bayoumi DM
TI - An epidemiologic study of ovarian cancer. Part 11: Oral contraceptive use and menstrual events.
SO - J Egypt Public Health Assoc 1992;67(5-6):579-91
AD - Department of Community Medicine, Faculty of Medicine, University of Alexandria, Egypt.
This work was conducted to investigate the potential risk factors which may contribute to the development of ovarian cancer. A retrospective analysis was adopted where 52 ovarian cancer cases and an equal number of a control group were obtained from the Western region of Saudi Arabia. This case-control study confirms that oral contraceptive use protects against the onset of ovarian cancer and that the decrease in the risk of the development of this disease is also directly related to the duration of use. Additionally, the study revealed a positive association between both age at menopause and hot flashes and the relative risk of ovarian cancer. On the contrary, age at menarche and premenstrual tension have been shown in this study to have no role as a risk factor in the development of ovarian cancer.
UI - 7304575
AU - Hildreth NG; Kelsey JL; LiVolsi VA; Fischer DB; Holford TR; Mostow ED;
TI - Schwartz PE; White C An epidemiologic study of epithelial carcinoma of the ovary.
SO - Am J Epidemiol 1981 Sep;114(3):398-405
A case-control study to identify risk factors for epithelial ovarian cancer was undertaken among women in the age group 45-74 years who had been admitted to seven hospitals in Connecticut between July, 1977, and March, 1979. Characteristics that were found to increase the risk of epithelial ovarian cancer included being white, never having been pregnant, having a late age at menopause, having a family history of cancer of the ovary or endometrium, and having a long estimated number of years of ovulation. Prior use of post-menopausal estrogens did not alter the risk for epithelial ovarian cancer, but there was some indication that oral contraceptives protect against ovarian cancer. Women with ovarian cancer were somewhat more likely to have had a history of an underactive thyroid and were somewhat less likely to have had a history of an overactive thyroid than controls, although these trends were not statistically significant.
UI - 7045417
AU - Rosenberg L; Shapiro S; Slone D; Kaufman DW; Helmrich SP; Miettinen OS;
TI - Stolley PD; Rosenshein NB; Schottenfeld D; Engle RL Jr Epithelial ovarian cancer and combination oral contraceptives.
SO - JAMA 1982 Jun 18;247(23):3210-2
The risk of epithelial ovarian cancer in relation to the use of combination oral contraceptives was evaluated in a case-control study of women younger than 60 years. Combination oral contraceptives were used by 35 (26%) of 136 cases and 187 (35%) of 539 controls. The relative risk estimate for combination oral contraceptive use was 0.6 (95% confidence interval, 0.4 to 0.9). The reduction in risk appeared to persist for as long as ten years after use had ceased and to be greater for longer durations of use, but these results were not statistically significant. The findings were not explained by parity or by other identified potential confounding factors. The results suggest that the use of combination oral contraceptives protects against epithelial ovarian cancer.
UI - 7121514
AU - Cramer DW; Hutchison GB; Welch WR; Scully RE; Knapp RC
TI - Factors affecting the association of oral contraceptives and ovarian cancer.
SO - N Engl J Med 1982 Oct 21;307(17):1047-51
We investigated the relation between epithelial ovarian cancer and the use of oral contraceptives in a case-control study of 144 white women under the age of 60 who had ovarian cancer and 139 white women under 60 who were selected from the general population. We observed a decreased risk for ovarian cancer associated with the use of oral contraceptives in subjects 40 through 59 years of age at the time of the study. The relative risk, adjusted for parity, was 0.11, with 95 per cent confidence limits of 0.04 to 0.33. In contrast to the findings in older women, a decreased risk for ovarian cancer associated with oral-contraceptive use was not found in women under 40. In this group, the adjusted relative risk associated with any use of oral contraceptives was 1.98, with 95 per cent confidence limits of 0.74 to 5.27. The lowest risk for ovarian cancer associated with the use of oral contraceptives was observed in older parous subjects and in women who had discontinued use more than 10 years previously.
UI - 6762965
AU - Bettochi S; Restaino A; Lucisano F; Orlando E; Ferreri R; Ierardi GM;
TI - Selvaggi L Epidemiological factors and prophylaxis of ovarian tumors.
SO - Eur J Gynaecol Oncol 1982;3(3):192-205
UI - 6681935
AU - Risch HA; Weiss NS; Lyon JL; Daling JR; Liff JM
TI - Events of reproductive life and the incidence of epithelial ovarian cancer.
SO - Am J Epidemiol 1983 Feb;117(2):128-39
Women resident in six counties of Washington and Utah for whom diagnoses of epithelial ovarian cancer were made during 1975-1979 were interviewed concerning their menstrual, reproductive and medical histories. For comparison, interviews were also obtained from a random sample of women living in the same countries. Logistic regression methods were used, and histories of childbearing, miscarriages, lactation, and (in Washington) usage of oral contraceptives were found to be associated with decreased risk of ovarian cancer; the estimated relative risks were, respectively, 0.88 per pregnancy (i.e., 0.88(2) for two pregnancies, etc.) (p = 0.016), 0.82 per miscarriage (p = 0.049), 0.79 per year of lactation (p = 0.034), and 0.89 per year of oral contraception (p = 0.009). In addition, it was observed that the magnitudes of the diminished risks from these exposures substantially exceeded those which would have been expected solely on the basis of their inhibition of ovulation (X2(5) = 21.5, p = 0.0006). On the other hand, the lack of association found between the occurrence of ovarian cancer and either total dose or total time of exposure to noncontraceptive estrogens, or with a history of usage of thyroid medications, suggests that periods of reduced pituitary gonadotrophin secretion fail to reduce risk of ovarian cancer. Thus, although pregnancy, lactation and oral contraception appear to offer some protection against the development of epithelial ovarian cancer, the reasons remain obscure.
UI - 3591776
AU - Franks AL; Lee NC; Kendrick JS; Rubin GL; Layde PM
TI - Cigarette smoking and the risk of epithelial ovarian cancer.
SO - Am J Epidemiol 1987 Jul;126(1):112-7
Cigarette smoking may affect each of the currently proposed mechanisms of ovarian carcinogenesis. Whether cigarette smoking has any effect on the development of ovarian cancer has not been adequately evaluated. To study this issue, the authors examined data from the Cancer and Steroid Hormone Study, a multicenter, case-control study of gynecologic cancers conducted between December 1, 1980, and December 31, 1982, in eight geographic areas of the United States. This analysis utilized data on 494 women with newly diagnosed epithelial ovarian cancer and 4,238 population-based control women 20-54 years of age. There was no association of epithelial ovarian cancer with dose of cigarette smoking, age smoking started, time since smoking started, or time since smoking last occurred. Simultaneous adjustment for age, parity, history of oral contraceptive use, and other potentially confounding factors did not alter these results.
UI - 3605266
AU - Stockwell HG; Lyman GH
TI - Cigarette smoking and the risk of female reproductive cancer.
SO - Am J Obstet Gynecol 1987 Jul;157(1):35-40
An epidemiologic study was conducted to evaluate the relationship between cigarette smoking and the risk of breast, endometrial, and ovarian cancers. Results indicated a clear reduction of risk for endometrial cancer among women aged 50 years and older who smoke cigarettes. Risks were significantly reduced among moderate smokers (odds ratio = 0.6), heavy smokers (odds ratio = 0.4), and former smokers (odds ratio = 0.6). No association was observed among women under age 50 years. When the relationship between cigarette smoking and breast cancer was investigated, no statistically significant association between cigarette smoking and the risk of breast cancer was observed except among women greater than 50 years who were light smokers only. There was also a nonstatistically significant increase in risk among younger women smoking more than two packs of cigarettes a day (odds ratio = 2.0), but overall there was no evidence of any relationship. Similarly, no association between ovarian cancer and cigarette smoking was apparent, although there was a nonsignificant increase in risk among women under age 50 years who smoked 40 or more cigarettes a day or were exsmokers.
UI - 6539067
AU - Nasca PC; Greenwald P; Chorost S; Richart R; Caputo T
TI - An epidemiologic case-control study of ovarian cancer and reproductive factors.
SO - Am J Epidemiol 1984 May;119(5):705-13
A population-based case-control study was conducted with 403 white, ovarian cancer patients, 20-79 years of age, who were diagnosed from study also included 806 controls who were matched to the cases by age, race, and county of residence. The contraceptive and reproductive patterns observed in this study suggest that infertility plays an important role in determining the relationship between reduced parity and gravidity and increased ovarian cancer risk. Ovarian cancer patients were less likely than controls to have ever used nonpermanent birth control methods (relative risk = 0.63, 95% confidence interval = 0.45-0.89), and they tended to practice contraception less often. A direct graded-response relationship was observed between ovarian cancer risk and the number of contraceptive-free years of marriage (chi 2 Linear trend = 5.911, p = 0.02). An inverse graded-response relationship was observed between gravidity and risk. This relationship persisted even after contraception was taken into account (chi 2 Linear trend = 13.002, p = 0.0003). Ovarian cancer risk was not found to be associated with an excess in reported fetal loss.
UI - 6488215
AU - Koch M; Starreveld AA; Hill GB; Jenkins H
TI - The effect of tubal ligation on the incidence of epithelial cancer of the ovary.
SO - Cancer Detect Prev 1984;7(4):241-5
A retrospective review of 666 women who underwent tubal ligation between 1930 and 1969 in Alberta, Canada, was undertaken to assess the effect of tubal ligation on the incidence of ovarian cancer. Tubal ligation did not affect the risk of ulterior ovarian cancer except in women who underwent tubal ligation between the ages of 20 and 29. These women showed a slight but statistically significant (p = 0.03) increase in observed versus expected cases of ovarian cancer.
UI - 6209226
AU - Nischan P; Ebeling K
TI - Oral contraceptives containing chlormadinone acetate and cancer incidence at selected sites in the German Democratic Republic--a correlation analysis.
SO - Int J Cancer 1984 Nov 15;34(5):671-4
The use of oral contraceptives containing chlormadinone acetate in 1972 by women of 13 districts (out of 15) of the GDR has been related to the incidence of cancer of breast, corpus uteri, and ovary during the period 1961 to 1980. Cancer incidence was represented by cohort parameters showing the risk of the cohorts in relation to each other. No statistically significant association between the two events was noted. Although not significant, our data are consistent with an elevated relative risk for breast cancer of 1.3 and a decreased risk for ovarian cancer of 0.5.