Hormone replacement therapy and risk of colon and rectal cancer.

The hypothesis that sex hormones may influence colorectal cancer risk was formulated in the early 1980s, but epidemiological studies on a relationship between colorectal cancer risk and hormone replacement therapy (HRT) have only accumulated over the last few years. To investigate the relationship between HRT and colon and rectal cancer and the role of other covariates that might modify it, we analyzed combined data from two case-control studies conducted in Italy between 1985 and 1996, including 994 women with incident colon cancer, 542 with rectal cancer, and 3110 controls with acute, non-neoplastic, nondigestive, non-hormone-related disorders. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived from unconditional multiple logistic regression equations including terms for age, center/study period, education, family history of colorectal cancer, status and age at menopause, parity, use of oral contraceptives, total energy intake, and body mass index. Ever use of HRT was inversely associated with cancer of the colon (OR = 0.64, 95% CI = 0.46-0.88) and of the rectum (OR = 0.46, 95% CI = 0.29-0.72). Increasing duration of use of HRT was related to decreasing risk for colon and rectal cancers (P for trend < 0.01). No interaction emerged, and the inverse association persisted across separate strata of other risk factors. This study, one of the largest case-control investigations on exogenous female hormones and colorectal cancer thus far, provides further evidence that women who have ever used HRT are at lower risk of colon and rectal cancer. Because colorectal cancer is the second most common neoplasm and cause of death among nonsmoking women in developed countries, these results may have a major public health impact.