A polymorphism in CYP17 and endometrial cancer risk

Among women, the A2 allele of CPP17 has been associated with elevated level s of endogenous steroid hormones; however, it does not seem to be a strong independent risk factor for breast cancer. We assessed the association betw een the A2 allele of CYP17 and invasive endometrial cancer risk in a case-c ontrol study nested within the Nurses' Health Study cohort tenses: n = 184; controls: II = 554), We also evaluated whether endometrial cancer risk ass ociated with CYP17 genotype was modified by established endometrial cancer risk factors, In addition, we further examined the relationship Between CYP 17 genotype and endogenous plasma steroid hormone levels among postmenopaus al controls not using hormone replacement therapy (HRT), Women with the A2 allele of CYP17 were at decreased risk of endometrial cancer (A1/A1 genotyp e (reference); A1/A2 genotype: odds ratio, 0.89; 95% confidence interval, 0 .62-1.27; A2/A2 genotype: odds ratio, 0.43; 95% confidence interval, 0.23-0 .80; P trend, 0.02). We also observed the inverse association between the A 2 allele and endometrial cancer risk to I,e stronger among women with a fir st-degree family history of endometrial and/or colorectal cancer (P for int eraction, 0.05). Among 165 controls, we did not observe women with the A2 a llele to have significantly elevated levels of any steroid hormone fraction . When these women were combined and analyzed with those women on whom we h ad previously examined the relationship between CYP17 genotype and circulat ing hormone levels (total II = 469), only modest associations were observed for the A2/A2 genotype and steroid hormone fractions estrone (ser sus A1/A 1 genotype: +10.9%; P = 0.05) and estradiol (+8.5%; P = 0.17), These data s uggest that the A2 allele of CYP17 decreases endometrial cancer risk, but h as only weak effects on endogenous estrogen levels among postmenopausal wom en.