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BackgroundIn 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.MethodsWe 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.ResultsParity 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.ConclusionsWe observed higher GBC risk with higher parity and shorter reproductive lifespan, suggesting an important role for reproductive and hormonal factors.

Original publication

DOI

10.1093/ije/dyab197

Type

Journal article

Journal

International journal of epidemiology

Publication Date

06/2022

Volume

51

Pages

789 - 798

Addresses

Section of Molecular Epidemiology and Population Genetics, Centre for Cancer Epidemiology, Tata Memorial Centre, Kharghar, Navi Mumbai, India.

Keywords

Humans, Gallbladder Neoplasms, Reproductive History, Risk Factors, Case-Control Studies, Parity, Pregnancy, Menopause, Menarche, Female