Circulating 2-hydroxy- and 16alpha-hydroxy estrone levels and risk of breast cancer among postmenopausal women.
Circulating 2-hydroxy- and 16alpha-hydroxy estrone levels and risk of breast cancer among postmenopausal women.
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DOI：
10.1158/1055-9965.epi-08-0262
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发表时间：
2008-08
期刊：
影响因子：
--
通讯作者：
Hankinson SE
中科院分区：
文献类型：
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作者：
Eliassen AH;Missmer SA;Tworoger SS;Hankinson SE
循环雌激素与绝经后妇女患乳腺癌的风险有关。鉴于雌激素代谢物具有潜在的促有丝分裂和遗传毒性，雌激素代谢物的血浆水平可能与乳腺癌风险相关。我们在护士健康研究中进行了一项前瞻性、巢式病例对照研究。1989-1990年对340例绝经后妇女和677例对照者进行了2-羟基雌酮和16α-羟基雌酮的测定。多变量相对危险度（RR）和95%置信区间（CI）通过条件Logistic回归计算，调整乳腺癌的危险因素。2-OH雌酮和16α-OH雌酮浓度均与总体乳腺癌风险无显著相关性（2-OH雌酮的上四分位数与下四分位数RR=1.19，95% CI（0.80-1.79），p趋势=0.40; 16α-OH雌酮的RR=1.04，95% CI（0.71-1.53），p趋势=0.81）。两种代谢产物（2：16α-OH雌酮）之间的比值与总体风险相似（1.30，95% CI（0.87-1.95），p趋势=0.35）。虽然在ER+/PR+肿瘤女性中未检测到相关性，但在ER-/PR-肿瘤女性中观察到2-OH雌酮和2：16α-OH雌酮比率的显著正相关性（2-OH雌酮RR=3.65 95% CI（1.23-10.81），p趋势=0.01，p异质性=0.02; 2：16α-OH雌酮RR=3.70，95% CI（1.24-11.09），p趋势=0.004，p异质性=0.005）。这些数据不支持与2-OH雌酮和2：16α-OH雌酮比例的假设负相关，也不支持与16α-OH雌酮的假设正相关。ER-/PR-肿瘤患者中2-OH雌酮和2：16 OH雌酮比例的显著正相关性需要在未来的研究中重复。
Circulating estrogens are associated with breast cancer risk in postmenopausal women. Given that estrogen metabolites are potentially both mitogenic and genotoxic, it is possible that plasma levels of estrogen metabolites are related to breast cancer risk. We conducted a prospective, nested case-control study within the Nurses' Health Study. Blood samples, collected in 1989-1990, were assayed for 2-OH estrone and 16α-OH estrone among 340 cases and 677 matched controls not taking postmenopausal hormones. Multivariate relative risks (RR) and 95% confidence intervals (CI) were calculated by conditional logistic regression, adjusting for breast cancer risk factors. Neither 2-OH estrone nor 16α-OH estrone concentrations were significantly associated with breast cancer risk overall (top vs. bottom quartile RR=1.19, 95% CI (0.80-1.79), p-trend=0.40 for 2-OH estrone and RR=1.04, 95% CI (0.71-1.53), p-trend=0.81 for 16α-OH estrone). The ratio between the two metabolites (2:16α-OH estrone) was similarly unrelated to risk overall (1.30, 95% CI (0.87-1.95), p-trend=0.35). While no associations were detected among women with ER+/PR+ tumors, significant positive associations were observed for 2-OH estrone and the 2:16α-OH estrone ratio among women with ER-/PR- tumors (2-OH estrone RR=3.65 95% CI (1.23-10.81), p-trend=0.01, p-heterogeneity=0.02; 2:16α-OH estrone RR=3.70, 95% CI (1.24-11.09), p-trend=0.004, p-heterogeneity=0.005). These data do not support the hypothesized inverse associations with 2-OH estrone and the 2:16α-OH estrone ratio nor the hypothesized positive association with 16α-OH estrone. The significant positive associations with 2-OH estrone and the 2:16 OH estrone ratio among women with ER-/PR- tumors needs to be replicated in future studies.