Tubal ligation and risk of ovarian cancer subtypes: A pooled analysis of case-control studies

Background: Tubal ligation is a protective factor for ovarian cancer, but it is unknown whether this protection extends to all invasive histological subtypes or borderline tumors. We undertook an international collaborative study to examine the association between tubal ligation and ovarian cancer subtypes. Methods: We pooled primary data from 13 population-based case-control studies, including 10 157 patients with ovarian cancer (7942 invasive; 2215 borderline) and 13 904 control women. Invasive cases were analysed by histological type, grade and stage, and borderline cases were analysed by histological type. Pooled odds ratios were estimated using conditional logistic regression to match on site, race/ethnicity and age categories, and to adjust for age, oral contraceptive use duration and number of full-term births. Results: Tubal ligation was associated with significantly reduced risks of invasive serous (OR, 0.81; 95% CI, 0.74-0.89; P<0.001),endometrioid (OR, 0.48; 95% CI, 0.40-0.59; P<0.001), clear cell (OR, 0.52; 95% CI, 0.40-0.67; P<0.001) and mucinous (OR, 0.68; 95% CI, 0.52-0.89; P1/4 0.005) cancers. The magnitude of risk reduction was significantly greater for invasive endometrioid (P<0.0001) and clear cell (P1/4 0.0018) than for serous cancer. No significant associations were found with borderline serous or mucinous tumours. Conclusions: We found that the protective effects of tubal ligation on ovarian cancer risk were subtype-specific. These findings provide insights into distinct aetiologies of ovarian cancer subtypes and mechanisms underlying the protective effects of tubal ligation.