Haiman C A, Hankinson S E, Spiegelman D, Colditz G A, Willett W C, Speizer F E, Kelsey K T, Hunter D J
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Cancer Res. 1999 Mar 1;59(5):1015-20.
The A2 allele of CYP17 has been associated with polycystic ovarian syndrome, elevated levels of certain steroid hormones in premenopausal women, and increased breast cancer risk. We prospectively assessed the association between the A2 allele of CYP17 and breast cancer risk in a case-control study nested within the Nurses' Health Study cohort. We also evaluated associations between this CYP17 genotype and plasma steroid hormone levels among postmenopausal controls not using hormone replacement to assess the biological significance of this genetic variant. Women with the A2 allele were not at an increased risk of incident breast cancer [OR (odds ratio), 0.85; 95% CI (confidence interval), 0.65-1.12] or advanced breast cancer (OR, 0.84; 95% CI, 0.54-1.32). We did observe evidence that the inverse association of late age at menarche with breast cancer may be modified by the CYP17 A2 allele. The protective effect of later age at menarche was only observed among women without the A2 allele (A1/A1 genotype: for age at menarche > or =13 versus <13; OR, 0.57; 95% CI, 0.36-0.90; A1/A2 and A2/A2 genotypes: OR, 1.05; 95% CI, 0.76-1.45; P for interaction = 0.07). Among controls, we found women with the A2/A2 genotype to have elevated levels of estrone (+14.3%, P = 0.01), estradiol (+13.8%, P = 0.08), testosterone (+8.6%, P = 0.34), androstenedione (+17.1%, P = 0.06), dehydroepiandrosterone (+14.4%, P = 0.02), and dehydroepiandrosterone sulfate (+7.2%, P = 0.26) compared with women with the A1/A1 genotype. These data suggest that the A2 allele of CYP17 modifies endogenous hormone levels, but is not a strong independent risk factor for breast cancer.
细胞色素P450 17α-羟化酶（CYP17）的A2等位基因与多囊卵巢综合征、绝经前女性某些甾体激素水平升高以及乳腺癌风险增加有关。在护士健康研究队列中的一项病例对照研究中，我们前瞻性地评估了CYP17的A2等位基因与乳腺癌风险之间的关联。我们还评估了这种CYP17基因型与未使用激素替代疗法的绝经后对照者血浆甾体激素水平之间的关联，以评估这种基因变异的生物学意义。携带A2等位基因的女性患乳腺癌的风险并未增加[比值比（OR）为0.85；95%置信区间（CI）为0.65 - 1.12]，患晚期乳腺癌的风险也未增加（OR为0.84；95%CI为0.54 - 1.32）。我们确实观察到有证据表明，初潮年龄较晚与乳腺癌之间的负相关可能会被CYP17 A2等位基因改变。初潮年龄较晚的保护作用仅在没有A2等位基因的女性中观察到（A1/A1基因型：初潮年龄≥13岁与＜13岁相比；OR为0.57；95%CI为0.36 - 0.90；A1/A2和A2/A2基因型：OR为1.05；95%CI为0.76 - 1.45；交互作用P值为0.07）。在对照者中，我们发现与A1/A1基因型的女性相比，A2/A2基因型的女性雌酮水平升高（+14.3%，P = 0.01）、雌二醇水平升高（+13.8%，P = 0.08）、睾酮水平升高（+8.6%，P = 0.34）、雄烯二酮水平升高（+17.1%，P = 0.06）、脱氢表雄酮水平升高（+14.4%，P = 0.02）以及硫酸脱氢表雄酮水平升高（+7.2%，P = 0.26）。这些数据表明，CYP17的A2等位基因会改变内源性激素水平，但并非乳腺癌的强独立危险因素。
