Lifetime body weight and premenopausal breast cancer

描述（由申请人提供）：出生体重和一生中不同时间点的体重被认为会影响绝经前乳腺癌的风险。高出生体重与绝经前乳腺癌的风险增加有关。更奇怪的是，儿童和成年早期的超重和肥胖一直与绝经前乳腺癌风险降低有关。这些关联的机制尚未阐明。体重和身体质量在生命的不同阶段如何在其对乳腺癌风险的影响中相互关联尚未得到充分探讨。一方面出生体重与另一方面儿童和青少年早期体重与绝经前乳腺癌风险之间的相反关系令人困惑。然而，评估乳腺癌的风险与这些人体测量因素在一生中是复杂的，因为不仅可能出生体重，儿童体重，在青春期和成年早期的体重相关，这些人体测量因素也可以影响其他变量，如初潮年龄，身高，这可能与以后的体重和乳腺癌的风险。此外，生物学途径之间的关联人体测量因素在一生中和绝经前乳腺癌的风险还没有得到很好的理解。在动物实验中，瘦素受体缺陷的肥胖啮齿动物不会患乳腺肿瘤。我们建议调查绝经前乳腺癌的风险与出生体重，5岁和10岁的相对体重，18岁时的体重指数（BMI）和成年早期更新的BMI，通过两年一次的随访，从1989年到2005年在护士健康研究II（NHS II）。我们进一步建议评估瘦素血浆水平和遗传多态性的瘦素基因和瘦素受体基因的巢式病例对照的方式。我们建议检查是否乳腺密度检测在乳房X光检查中可能是一个时间依赖性的混杂因素或影响修饰符之间的关联体重和绝经前乳腺癌。这将是第一项采用生命过程方法将体重与乳腺癌发病率联系起来的研究。它也是高效的，因为它借鉴了已经为NHS II收集的问卷数据，血液样本和乳房X光照片。

DESCRIPTION (provided by applicant): Birth weight and body weight at various points during lifetime have being suggested to influence the risk of premenopausal breast cancer. A high birth weight has been associated with an increased risk of premenopausal breast cancer. More curiously, overweight and obesity during childhood and early adulthood have consistently been linked to a decreased risk of premenopausal breast cancer. The mechanisms underlying these associations have not been elucidated. How body weight and body mass at different stages in life may interrelate in their impact on breast cancer risk has not been sufficiently explored. The opposite direction of the association of birth weight on one hand and of childhood and early adolescent body mass on the other hand with premenopausal breast cancer risk is perplexing. However, evaluating breast cancer risk in relation to these anthropometric factors during lifetime is complicated because not only may birth weight, childhood weight, and body mass during adolescence and early adulthood be related, these anthropometric factors can also influence other variables, such as age at menarche, height, which may be related to both later body mass and the risk of breast cancer. Furthermore, biological pathways underlying the association between anthropometric factors during lifetime and premenopausal breast cancer risk are not well understood. In animal experiments, obese rodents with a defect in the leptin receptor did not develop mammary tumors. We propose to investigate premenopausal breast cancer risk in relation to birth weight, relative weight at age 5 and 10, body mass index (BMI) at age 18 and updated BMI in early adulthood through biannual follow-up from 1989 through 2005 in the Nurses' Health Study II (NHS II). We further propose to evaluate leptin plasma levels and genetic polymorphisms of the leptin gene and the leptin receptor gene in a nested case-control fashion. We propose to examine whether breast density as detected in a mammogram may be an time-dependent confounder or an effect modifier of the association between body mass and premenopausal breast cancer. This will be the first study taking a life-course approach in linking body mass with breast cancer incidence. It is also highly efficient since it borrows from questionnaire data, blood samples, and mammograms already collected for the NHS II.