绝经后女性的体重指数、血清性激素与乳腺癌风险

Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women.

作者信息

Key T J, Appleby P N, Reeves G K, Roddam A, Dorgan J F, Longcope C, Stanczyk F Z, Stephenson H E, Falk R T, Miller R, Schatzkin A, Allen D S, Fentiman I S, Key T J, Wang D Y, Dowsett M, Thomas H V, Hankinson S E, Toniolo P, Akhmedkhanov A, Koenig K, Shore R E, Zeleniuch-Jacquotte A, Berrino F, Muti P, Micheli A, Krogh V, Sieri S, Pala V, Venturelli E, Secreto G, Barrett-Connor E, Laughlin G A, Kabuto M, Akiba S, Stevens R G, Neriishi K, Land C E, Cauley J A, Kuller L H, Cummings S R, Helzlsouer K J, Alberg A J, Bush T L, Comstock G W, Gordon G B, Miller S R, Longcope C

机构信息

Cancer Research U.K. Epidemiology Unit, University of Oxford, Gibson Bldg., Radcliffe Infirmary, Oxford OX2 6HE, UK.

出版信息

J Natl Cancer Inst. 2003 Aug 20;95(16):1218-26. doi: 10.1093/jnci/djg022.

DOI:10.1093/jnci/djg022

PMID:12928347

Abstract

BACKGROUND

Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations.

METHODS

We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case-control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two-sided.

RESULTS

Breast cancer risk increased with increasing BMI (P(trend) =.002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m2 increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-sex hormone-binding globulin-bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk.

CONCLUSION

The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol.

摘要

背景

肥胖与绝经后女性患乳腺癌风险增加相关。我们研究了这种关联是否可由体重指数（BMI）与血清性激素浓度之间的关系来解释。

方法

我们分析了八项绝经后女性前瞻性研究的个体数据。624例病例受试者和1669例对照受试者有BMI和诊断前雌二醇水平的数据；其他性激素的数据可获得的受试者较少。通过对病例对照数据集进行条件逻辑回归估计与BMI增加相关的乳腺癌的相对风险（RRs）及其95%置信区间（CIs），在每项研究中按年龄和招募日期进行匹配，并对产次进行调整。所有统计检验均为双侧检验。

结果

乳腺癌风险随BMI增加而增加（P趋势=0.002），通过调整血清雌激素浓度，RR的这种增加显著降低。调整游离雌二醇后，与BMI增加5kg/m²相关的乳腺癌RR从（95%CI=1.05至1.34）降至1.02（95%CI=0.89至1.17）。调整其他雌激素（总雌二醇、非性激素结合球蛋白结合雌二醇、雌酮和硫酸雌酮）后，增加的风险也显著降低，调整性激素结合球蛋白后风险适度降低，而调整雄激素（雄烯二酮、脱氢表雄酮、硫酸脱氢表雄酮和睾酮）对额外风险影响很小。