Reproductive factors and gall-bladder cancer, and the effect of common genetic variants on these associations: a case–control study in India. (22nd September 2021)

• Record Type: Journal Article
• Authors: Mhatre, Sharayu; Lacey, Ben; Sherliker, Paul; Chatterjee, Nilanjan; Rajaraman, Preetha; Goel, Mahesh; Patkar, Shraddha; Ostwal, Vikas; Patil, Prachi; Shrikhande, Shailesh V; Chitkara, Garvit; Badwe, Rajendra; Lewington, Sarah; Dikshit, Rajesh
• Is Part Of: International journal of epidemiology. Volume 51:Number 3(2022)
• Page Start: 789
• Page End: 798
• Publication Date: 2021-09-22
• Subjects: Gall-bladder cancer -- pregnancy -- breastfeeding -- menarche -- menopause -- case–control; Epidemiology -- Periodicals; 614.4
• DOI: 10.1093/ije/dyab197
• Languages: English
• ISSNs: 0300-5771

Abstract

Abstract: 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.