Reproductive factors and gall-bladder cancer, and the effect of common genetic variants on these associations: A case-control study in India

Sharayu Mhatre, Ben Lacey, Paul Sherliker, Nilanjan Chatterjee, Preetha Rajaraman, Mahesh Goel, Shraddha Patkar, Vikas Ostwal, Prachi Patil, Shailesh V. Shrikhande, Garvit Chitkara, Rajendra Badwe, Sarah Lewington, Rajesh Dikshit

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)789-798
Number of pages10
JournalInternational journal of epidemiology
Volume51
Issue number3
DOIs
StatePublished - Jun 1 2022

Keywords

  • Gall-bladder cancer
  • breastfeeding
  • case-control
  • menarche
  • menopause
  • pregnancy

ASJC Scopus subject areas

  • Epidemiology

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