Association of female reproductive and hormonal factors with gallbladder cancer risk in Asia: A pooled analysis of the Asia Cohort Consortium

Int J Cancer. 2024 Jul 15;155(2):240-250. doi: 10.1002/ijc.34916. Epub 2024 Mar 13.

Abstract

The female predominance of gallbladder cancer (GBC) has led to a hypothesis regarding the hormone-related aetiology of GBC. We aimed to investigate the association between female reproductive factors and GBC risk, considering birth cohorts of Asian women. We conducted a pooled analysis of 331,323 women from 12 cohorts across 4 countries (China, Japan, Korea, and Singapore) in the Asia Cohort Consortium. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) to assess the association between reproductive factors (age at menarche, parity, age at first delivery, breastfeeding, and age at menopause) and GBC risk. We observed that a later age at menarche was associated with an increased risk of GBC (HR 1.4, 95% CI 1.16-1.70 for 17 years and older vs. 13-14 years), especially among the cohort born in 1940 and later (HR 2.5, 95% CI 1.50-4.35). Among the cohort born before 1940, women with a later age at first delivery showed an increased risk of GBC (HR 1.56, 95% CI 1.08-2.24 for 31 years of age and older vs. 20 years of age and younger). Other reproductive factors did not show a clear association with GBC risk. Later ages at menarche and at first delivery were associated with a higher risk of GBC, and these associations varied by birth cohort.

Keywords: birth cohort; delivery; menarche; menopause; pooled analysis.

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Asia / epidemiology
  • Cohort Studies
  • Female
  • Gallbladder Neoplasms* / epidemiology
  • Gallbladder Neoplasms* / etiology
  • Humans
  • Menarche*
  • Menopause
  • Middle Aged
  • Parity
  • Proportional Hazards Models
  • Reproductive History
  • Risk Factors