Reproductive factors in the risk of bladder cancer and upper urinary tract cancer: The Japan Public Health Center-based Prospective Study.

Abstract

Reproductive factors are hypothesized to play a role in the incidence of bladder cancer (BC) and upper urinary tract cancer (together, urothelial cancer (UC)). However, evidence regarding these associations is limited, particularly in Asian populations. We analyzed data from 55,882 females aged 40-69 years, and performed Cox proportional hazards regression analyses with three types of adjustment, namely age; reproductive factor of interest and covariates in addition to age (conventional model); and other reproductive factors in addition to the multivariable adjusted model (reproductive model). During an average of 20.2 years of follow-up, 194 UC cases (145 BC cases and 49 UUTC cases) were identified. Early age at natural menopause (<44 years, compared to 49-51 years) increased BC risk in the reproductive model (HR=2.09 (95% CI=1.04-4.20)). An association between UC/BC and age at menopause, including both natural and surgical/induced, was significant in the reproductive model [HR=1.74 (95% CI=1.09-2.77), and HR=1.94 (95% CI=1.15-3.28), respectively]. Early age at natural menopause was suggested to increase UC risk in the reproductive model (HR=1.78 (95% CI=0.93-3.42)). Our findings suggest a significant association between age at menopause and incidence of UC/BC among Asian populations. This study aids understanding the role of reproductive factors in UC/BC incidence. In Japanese populations, age at menopause is suggested to be associated with UC/BC incidence, especially regarding early natural menopause.