Reproductive factors and gallbladder/bile duct cancer: a population-based cohort study in Japan

Reproductive/menstrual factors may be involved in the etiology of gallbladder cancer (GBC) and bile duct cancer (BDC). However, the results from previous epidemiological studies have been inconsistent. We investigated the association of reproductive/menstrual factors with the risk for GBC and BDC in a population-based prospective cohort study in Japan. Data on reproductive/menstrual factors were collected through a self-administered questionnaire at baseline. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazard model. A total of 55 786 women enrolled between 1990 and 1994 were included in the analysis, and 115 GBC and 113 BDC cases were identified, with 944 861 person-years follow-up until 2010. For GBC, irregular and longer cycles were moderately associated with an increased risk [HR=2.12 (95% CI: 1.30-3.47) and HR=1.76 (95% CI: 1.08-2.89), respectively]. This effect tended to be greater in premenopausal than in postmenopausal women. Furthermore, older age at first pregnancy tended to be associated with an increased risk [HR=1.84 (95% CI: 1.03-3.29), P-trend=0.036], whereas increased duration of fertility tended to be associated with a decreased risk [HR=0.59 (95% CI: 0.35-1.01), P-trend=0.055] of GBC. No clear association with BDC was observed. This finding suggests that women with irregular or longer cycles may have an increased risk for GBC and female hormones may play an important role in the etiology of GBC.