Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies.

BACKGROUND: Half the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therapy on ovarian cancer risk. METHODS: Individual participant datasets from 52 epidemiological studies were analysed centrally. The principal analyses involved the prospective studies (with last hormone therapy use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies. Adjusted Poisson regressions yielded relative risks (RRs) versus never-use. FINDINGS: During prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with <5 years of use (RR 1·43, 95% CI 1·31-1·56; p<0·0001). Combining current-or-recent use (any duration, but stopped <5 years before diagnosis) resulted in an RR of 1·37 (95% CI 1·29-1·46; p<0·0001); this risk was similar in European and American prospective studies and for oestrogen-only and oestrogen-progestagen preparations, but differed across the four main tumour types (heterogeneity p<0·0001), being definitely increased only for the two most common types, serous (RR 1·53, 95% CI 1·40-1·66; p<0·0001) and endometrioid (1·42, 1·20-1·67; p<0·0001). Risk declined the longer ago use had ceased, although about 10 years after stopping long-duration hormone therapy use there was still an excess of serous or endometrioid tumours (RR 1·25, 95% CI 1·07-1·46, p=0·005). INTERPRETATION: The increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for 5 years from around age 50 years have about one extra ovarian cancer per 1000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1700 users. FUNDING: Medical Research Council, Cancer Research UK

Reproductive factors for ovarian cancer in southern Chinese women

Objective: To investigate the association between reproductive factors and the risk of ovarian cancer among southern Chinese women. Methods: A hospital-based case-control study was undertaken in Guangzhou, Guangdong Province, between 2006 and 2008. A structured questionnaire was used to obtain information on parity, oral contraceptive use and other reproductive factors in a sample of 500 incident ovarian cancer patients and 500 controls (mean age, 59 years). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression models. Results: High parity was inversely associated with ovarian cancer, with an adjusted OR 0.43 (95% CI, 0.30 to 0.62) for women who had given birth to 3 or more children compared to women who had given no more than one birth. Ever use of oral contraceptives was also protective against ovarian cancer; adjusted OR 0.56 (95% CI, 0.40 to 0.78). No association was found for hormone replacement therapy, menopausal status, hysterectomy and family history of ovarian and/or breast cancer. Conclusion: High parity and oral contraceptive use are associated with a lower risk of ovarian cancer in southern Chinese women

Relative risk of ovarian cancer by tumour histology.

<p>Relative risk¹ (RR¹) is stratified by study, age at diagnosis, parity, menopausal status/hysterectomy, body mass index, duration of oral contraceptive use, and ever use of hormone therapy. Relative risk² (RR²) is stratified by study, age at diagnosis, parity, menopausal status/hysterectomy, height, duration of oral contraceptive use, and ever use of hormone therapy. Case–control studies with hospital controls are excluded. The dotted line represents the overall result for all women with recorded histology. NOS, not otherwise specified; SE, standard error.</p

Relative risk of ovarian cancer in relation to height, weight, and body mass index.

<p>Test for trend: height, <i>p</i><0.001; weight, <i>p</i><0.001; body mass index, <i>p</i><0.001. Studies with hospital controls are excluded.</p>a<p>Relative risk stratified by study, age at diagnosis, parity, menopausal status/hysterectomy, duration of oral contraceptive use, and ever use of menopausal hormone therapy.</p>b<p>Relative risk stratified as for the previous column, with additional stratification by body mass index (for height) and by height (for weight and body mass index).</p

Relative risk of ovarian cancer in relation to height and BMI in various subgroups of women.

<p>Relative risk¹ (RR¹) is stratified by study, age at diagnosis, parity, menopausal status/hysterectomy, body mass index, duration of oral contraceptive use, and ever use of hormone therapy (HT). Relative risk² (RR²) is stratified by study, age at diagnosis, parity, menopausal status/hysterectomy, height, duration of oral contraceptive use, and ever use of hormone therapy. ^† numbers do not always add to the total because of missing values; ^‡ never-user of hormone therapy. Case–control studies with hospital controls are excluded. The dotted line represents the overall result for all women. SE, standard error.</p

Relative risk of ovarian cancer by height.

<p>Relative risk compared to women with height <160 cm and stratified by study, age at diagnosis, parity, menopausal status/hysterectomy, body mass index, duration of oral contraceptive use, and ever use of hormone therapy. Relative risk estimates are plotted against the mean height in each category (<160, 160–164, 165–169, and 170+ cm). Case–control studies with hospital controls are excluded.</p

Ovarian cancer and smoking: individual participant meta-analysis including 28 114 women with ovarian cancer from 51 epidemiological studies

BACKGROUND: Smoking has been linked to mucinous ovarian cancer, but its effects on other ovarian cancer subtypes and on overall ovarian cancer risk are unclear, and the findings from most studies with relevant data are unpublished. To assess these associations, we review the published and unpublished evidence. METHODS: Eligible epidemiological studies were identified by electronic searches, review articles, and discussions with colleagues. Individual participant data for 28 114 women with and 94 942 without ovarian cancer from 51 epidemiological studies were analysed centrally, yielding adjusted relative risks (RRs) of ovarian cancer in smokers compared with never smokers. FINDINGS: After exclusion of studies with hospital controls, in which smoking could have affected recruitment, overall ovarian cancer incidence was only slightly increased in current smokers compared with women who had never smoked (RR 1.06, 95% CI 1.01-1.11, p=0.01). Of 17 641 epithelial cancers with specified histology, 2314 (13%) were mucinous, 2360 (13%) endometrioid, 969 (5%) clear-cell, and 9086 (52%) serous. Smoking-related risks varied substantially across these subtypes (p(heterogeneity)<0.0001). For mucinous cancers, incidence was increased in current versus never smokers (1.79, 95% CI 1.60-2.00, p<0.0001), but the increase was mainly in borderline malignant rather than in fully malignant tumours (2.25, 95% CI 1.91-2.65 vs 1.49, 1.28-1.73; p(heterogeneity)=0.01; almost half the mucinous tumours were only borderline malignant). Both endometrioid (0.81, 95% CI 0.72-0.92, p=0.001) and clear-cell ovarian cancer risks (0.80, 95% CI 0.65-0.97, p=0.03) were reduced in current smokers, and there was no significant association for serous ovarian cancers (0.99, 95% CI 0.93-1.06, p=0.8). These associations did not vary significantly by 13 sociodemographic and personal characteristics of women including their body-mass index, parity, and use of alcohol, oral contraceptives, and menopausal hormone therapy. INTERPRETATION: The excess of mucinous ovarian cancers in smokers, which is mainly of tumours of borderline malignancy, is roughly counterbalanced by the deficit of endometrioid and clear-cell ovarian cancers. The substantial variation in smoking-related risks by tumour subtype is important for understanding ovarian carcinogenesis.