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 ∼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.