VITAMIN D RECEPTOR GENE POLYMORPHISM AND BREAST CANCER

实验证据和生态相关性研究支持 假设维生素D可以降低患乳腺癌的风险。然而，这部小说 假说在很大程度上没有在人类群体中得到检验。一个正在进行的 西班牙裔乳腺癌的人群病例对照研究， 非裔美国人和白人妇女将评估与 日光照射和膳食维生素D摄入量。正在进行的分子 其中一项对这种应用的调查表明， 维生素D受体(VDR)基因的多态性与 乳腺癌风险。因此，我们建议扩大正在审理的案件范围： 对照研究，以扩大我们对与 维生素D。除了正在收集的采访数据外，我们建议 获取研究参与者子集的血液样本，并扩展 将案件和控制情况确定为10个月。符合条件的个案将 包括年龄在35-79岁并被诊断为浸润性乳腺癌的女性 1997年5月至1999年2月期间。病例将通过 大旧金山湾区的癌症登记；控制将 通过随机数字拨号从普通人群中选择。 专业面试者将收集面试数据，测量皮肤 并通过家访获取血液样本。血样 估计将有640份样本和风险因素数据可用 案例(245名西班牙裔、225名白人和170名非裔美国人)和960名 对照组(365名西班牙裔，340名白人和255名非裔美国人)。我们会 评估(1)与VDR的两个标记物(PolyA和FokI)的相关性 西班牙裔和白人的基因；(2)与BsmI/PolyA的关联 非裔美国人的单倍型；以及(3)可能的修饰作用 维生素D受体基因与日光照射和饮食的关系 维生素D摄入量。我们还会储存DNA，巴菲大衣和血浆 未来的分子流行病学研究。以基础设施为基础 在正在进行的研究中，我们有机会建立一个有价值的 更彻底地评估维生素之间关系的资源 D和乳腺癌风险；用于进行未来的分子流行病学 作为新的生物标志物和基因的研究将在未来被确定； 并研究多种族的基因与环境的相互作用 人口。由于维生素D的暴露可能是可改变的， 拟议的研究可能会对新的方法产生重要影响 预防乳腺癌。

Experimental evidence and ecologic correlation studies support the hypothesis that vitamin D may reduce breast cancer risk. Yet this novel hypothesis is largely untested in human populations. An on-going population-based case-control study of breast cancer in Hispanic, African-American, and White Women will assess the associations with sunlight exposure and dietary vitamin D intake. On-going molecular research by one of the investigations of this applications suggests that polymorphisms of the vitamin D receptor (VDR) gene are related to the breast cancer risk. We therefore propose to expand the on-going case- control study in order to broaden our examination of the relation with vitamin D. In addition to the interview data being collected, we propose to obtain blood samples for a subset of study participants and to extend the case and control ascertainment by 10 months. Eligible cases will include women aged 35-79 and diagnosed with invasive breast cancer between May 1997 and February 1999. Cases will be identified through the cancer registries in the Greater San Francisco Bay area; controls will be selected from the general population through random-digit dialing. Professional interviewers will collect interview data, measure skin pigmentation, and obtain blood specimens through home visits. Blood specimens and risk factor data will be available for an estimated 640 cases (245 Hispanics, 225 Whites, and 170 African-Americans) and 960 controls (365 Hispanics, 340 Whites, and 255 African-Americans). We will assess (1) the association with two markers (poly-A and FOKI) of the VDR gene in Hispanics and Whites; (2) the association with the BsmI/poly-A haplotype in African-Americans; and (3) the possible modifying effect of VDR genotype on the association with sunlight exposure and dietary vitamin D intake. We will also bank DNA, buffy coat, and plasma for future molecular epidemiologic studies. Building upon the infrastructure of the on-going study, we have the opportunity to establish a valuable resource for more thoroughly assessing the relationship between vitamin D and breast cancer risk; for conducting future molecular epidemiologic research as new biomarkers and genes will be identified in the future; and for investigating gene-environment interactions in a multi-ethnic population. Since vitamin D exposure is potentially modifiable, the proposed research may have important implications for new approaches to breast cancer prevention.