Reproductive Factors and Gall-Bladder Cancer, and the Effect of Common Genetic Variants on These Associations: a Case-Control Study in India.

Background In India, as elsewhere, the incidence of gall-bladder cancer (GBC) is substantially higher in women than in men. Yet, the relevance of reproductive factors to GBC remains poorly understood. Methods We used logistic regression adjusted for age, education and area to examine associations between reproductive factors and GBC risk, using 790 cases of histologically confirmed GBC and group-matched 1726 visitor controls. We tested the interaction of these associations by genetic variants known to increase the risk of GBC. Results Parity was strongly positively associated with GBC risk: each additional pregnancy was associated with an similar to 25% higher risk {odds ratio [OR] 1.26 [95% confidence interval (95% CI) 1.17-1.37]}. After controlling for parity, GBC risk was weakly positively associated with later age of menarche [postmenopausal women, OR 1.11 (95% CI 1.00-1.22) per year], earlier menopause [OR 1.03 (95% CI 1.00-1.06) per year] and shorter reproductive lifespan [OR 1.04 (95% CI 1.01-1.07) per year], but there was little evidence of an association with breastfeeding duration or years since last pregnancy. Risk alleles of single-nucleotide polymorphisms in the ABCB4 and ABCB1 genetic regions had a multiplicative effect on the association with parity, but did not interact with other reproductive factors. Conclusions We observed higher GBC risk with higher parity and shorter reproductive lifespan, suggesting an important role for reproductive and hormonal factors.