Gene Polymorphisms in Relation to Cancer in Black Women

描述（由申请人提供）：越来越多的证据表明，对癌症的易感性可能部分由低外显率基因决定，例如参与激素合成和代谢或有毒物质代谢的基因。许多这些基因已被发现是多态的，有不同的作用取决于多态性。在某些情况下，多态性的频率因种族和民族而异。基因-环境相互作用的研究将遗传信息与生殖因素、行为、药物使用和其他暴露的标准流行病学数据相结合，有可能极大地促进我们目前对人类癌症病因的理解。我们建议通过获取尽可能多的参加黑人妇女健康研究（BWHS）的非裔美国妇女的脸颊细胞样本来建立一个DNA库，BWHS是1995年开始的一项前瞻性随访研究。自入职以来，每两年通过邮寄问卷的方式获得有关生殖史、个人习惯和行为、药物使用、癌症和其他严重疾病发生的数据。最近的一项试验表明，参与者愿意通过邮寄的方式提供DNA样本，方法是用漱口水漱口，将其排出到一个小容器中，然后直接邮寄到实验室。DNA产率高，进行了成功的pcr。我们建议向约57,000名已完成至少一份跟进问卷的BWHS参与者邮寄漱口水样本；估计将有3.6万名女性提供样本。DNA将被提取并储存在参与实验的实验室。在2005年，将进行巢式病例对照分析，研究乳腺癌风险与几个参与雌激素代谢的基因和一个参与胰岛素样生长因子调节的基因的关系。DNA库将作为基因效应和基因-环境相互作用研究的资源，用于单独的BWHS数据以及与其他大型队列研究的联合或合并分析。BWHS将提供有关黑人女性基因与环境相互作用的最大数据来源，并将对任何种族的年轻女性的可用数据做出重大贡献。

DESCRIPTION (provided by applicant): Increasing evidence suggests that susceptibility to cancer may be determined in part by low-penetrance genes, such as genes involved in the synthesis and metabolism of hormones or the metabolism of toxic substances. Many of these genes have been found to be polymorphic, with different actions depending on the polymorphism. In some cases, the frequencies of polymorphisms differ by race and ethnicity. Studies of gene-environment interactions which combine genetic information with standard epidemiologic data on reproductive factors, behaviors, medication use, and other exposures have the potential to greatly advance our current understanding of the etiology of human cancer. We propose to establish a DNA repository by obtaining cheek cell samples from as many as possible of the African-American women enrolled in the Black Women's Health Study (BWHS), a prospective follow-up study begun in 1995. Every two years since entry, mail questionnaires have been used to obtain data on reproductive history, personal habits and behaviors, medication use, and the occurrence of cancer and other serious illness. A recent pilot demonstrated the willingness of participants to provide a DNA sample by mail by swishing the mouth with mouthwash, expelling it into a small container, and mailing it directly to a laboratory. The DNA yields were high, and successful PCRs were carried out. We propose to seek mouthwash samples by mail from the approximately 57,000 BWHS participants who have completed at least one follow-up questionnaire; an estimated 36,000 women will provide samples. DNA will be extracted and stored at the participating laboratory. During year 05, nested case-control analyses will be carried out of breast cancer risk in relation to several genes involved in estrogen metabolism and a gene involved in the regulation of insulin-like growth factor. The DNA repository will serve as a resource for studies of gene effects and gene-environment interactions in relation to cancer in BWHS data alone and in combined or pooled analyses with other large cohort studies. The BWHS will provide the largest source of data on gene-environment interactions in black women, and will contribute substantially to the data available on young women of any race.