Gene Polymorphisms in Relation to Cancer in Black Women

描述(申请人提供)：越来越多的证据表明，癌症的易感性可能部分由低外显性基因决定，例如参与激素合成和新陈代谢或有毒物质新陈代谢的基因。这些基因中的许多都被发现是多态的，不同的多态有不同的作用。在某些情况下，多态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、用药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学的理解。我们建议通过从参加黑人妇女健康研究(BWHS)的尽可能多的非裔美国女性获取脸颊细胞样本来建立DNA储存库。BWHS是一项始于1995年的前瞻性后续研究。自加入以来，每两年通过邮寄问卷获得生育史、个人习惯和行为、用药情况以及癌症和其他严重疾病的发生情况等数据。最近的一项试验表明，参与者愿意通过邮寄方式提供DNA样本，方法是用漱口水喷出嘴巴，将其排入一个小容器，然后直接邮寄到实验室。DNA产量高，并成功地进行了PCRS。我们建议通过邮寄方式向至少完成一份后续调查问卷的大约57,000名BWHS参与者寻求漱口水样本；估计有36,000名妇女将提供样本。DNA将被提取并存储在参与的实验室中。在05年，将对乳腺癌风险进行嵌套病例对照分析，这些分析与几个涉及雌激素代谢的基因和一个涉及胰岛素样生长因子调节的基因有关。DNA储存库将作为一个资源，单独在BWHS数据中研究与癌症有关的基因效应和基因-环境相互作用，并与其他大型队列研究结合或合并分析。BWHS将提供黑人女性基因-环境相互作用的最大数据来源，并将为任何种族的年轻女性可用的数据做出重大贡献。

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.