Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Cancer Prev Res (Phila). 2011 Sep;4(9):1449-56. doi: 10.1158/1940-6207.CAPR-11-0125. Epub 2011 Jun 16.
Body mass index (BMI) is inversely related to the risk of premenopausal breast cancer, but the underlying biological mechanisms of this association are poorly understood. Leptin, a peptide hormone produced primarily by adipocytes, is a potential mediator of the BMI association because BMI and total body fat are positively associated with circulating leptin levels and leptin and its receptor are overexpressed in breast tumors. We conducted a prospective case-control study nested within the Nurses' Health Study II cohort examining the association between plasma leptin levels in premenopausal women and breast cancer risk. Leptin was measured in blood samples collected between 1996 and 1999. The analysis included 330 incident breast cancer cases diagnosed after blood collection and 636 matched controls. Logistic regression models, controlling for breast cancer risk factors, were used to calculate ORs and 95% CIs. After adjustment for BMI at age 18, weight change since age 18 to blood draw, and other breast cancer risk factors, plasma leptin levels were inversely associated with breast cancer risk (OR for top vs. bottom quartile = 0.55; 95% CI = 0.31-0.99; P(trend) = 0.04). Adjustment for BMI at blood draw attenuated the association (OR = 0.69; 95% CI = 0.38-1.23; P(trend) = 0.26). Our results suggest that leptin may be inversely associated with breast cancer risk, but it is unclear whether any part of this association is independent of BMI.
体重指数（BMI）与绝经前乳腺癌的风险呈负相关，但这种关联的潜在生物学机制尚不清楚。瘦素是一种主要由脂肪细胞产生的肽激素，是 BMI 关联的潜在介质，因为 BMI 和全身脂肪与循环瘦素水平呈正相关，并且瘦素及其受体在乳腺癌肿瘤中过度表达。我们进行了一项前瞻性病例对照研究，该研究嵌套在护士健康研究 II 队列中，研究了绝经前妇女血浆瘦素水平与乳腺癌风险之间的关系。在 1996 年至 1999 年之间采集的血液样本中测量了瘦素。该分析包括 330 例在采血后诊断出的乳腺癌病例和 636 例匹配的对照。使用 logistic 回归模型，控制乳腺癌危险因素，计算了 OR 和 95％CI。在调整了 18 岁时的 BMI、18 岁以来的体重变化以及其他乳腺癌危险因素后，血浆瘦素水平与乳腺癌风险呈负相关（最高与最低四分位数的 OR = 0.55；95％CI = 0.31-0.99；P（趋势）= 0.04）。调整采血时的 BMI 会减弱这种关联（OR = 0.69；95％CI = 0.38-1.23；P（趋势）= 0.26）。我们的结果表明，瘦素可能与乳腺癌风险呈负相关，但尚不清楚这种关联的任何部分是否独立于 BMI。
