In this case-control study nested in a large cohort of postmenopausal women, we undertook a comprehensive evaluation of common and putative functional variants in the genes encoding estrogen and progesterone receptors (ESR1, ESR2, PGR) and enzymes responsible for critical steps in the conversion of progesterone or androgens to estrogens (CYP19A1 and CYP17A1) and in the formation of active estrogens (HSD17B1, HSD17B2, HSD17B4) in relation to colorectal cancer risk. The gene discussed is ESR1; the disease is colorectal cancer.