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.
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