Circulating sex hormone levels and colorectal cancer risk in Japanese postmenopausal women: The JPHC nested case–control study

Previous epidemiological studies evaluated endogenous sex hormone levels and colorectal cancer (CRC) risk have yielded inconsistent results. Also, it is unknown if consumption of dietary isoflavones may influence the endogenous sex hormones and CRC relationships. We conducted a nested case–control study within the JPHC Study Cohort II wherein 11,644 women provided blood samples at the 5-year follow-up survey. We selected two matched controls for each case from the cohort (185 CRC cases and 361 controls). Multivariable conditional logistic regression was used to estimate odds ratios (ORs), 95% confidence intervals (CIs) for the association between circulating sex hormone levels and CRC risk. Comparing extreme tertiles, circulating testosterone levels were positively associated with CRC risk (OR = 2.10, 95% CI = 1.11–3.99, p for trend = 0.03). Levels of estradiol, SHBG, and progesterone were not associated with CRC risk. In a subgroup analysis by dietary isoflavone intake, SHBG levels were positively associated with CRC risk among those with low total isoflavone intake (p for trend = 0.03), with a statistically nonsignificant inverse association among those with high total isoflavone intake (p for trend = 0.22; p for interaction = 0.002). Endogenous levels of testosterone were positively associated with CRC among postmenopausal women. The association of endogenous SHBG with CRC development may be altered by the level of dietary isoflavone intake.