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The long term goal of the proposed research is to identify a subgroup of women who are at a higher risk of breast cancer due to defective metabolism of environmental carcinogens. N-acetyltransferase (NAT2) is a hepatic enzyme which metabolizes carcinogens such as aromatic amines, which are constituents of tobacco smoke. The present study aims: 1) to explore the association between polymorphisms of NAT2 gene and breast cancer; and, 2) to examine the effect of cigarette smoking on breast cancer with respect to NAT2 genotypic status (slow and rapid acetylators) among a population-based sample of women participating in the ongoing Long Island Breast Cancer Study Project (LIBCSP). The parent LIBCSP study is expected to recruit and collect data from about 1600 newly diagnosed breast cancer cases and 1600 controls and is already funded for the laboratory analyses of environmental carcinogens including organochlorine pesticides, PAH-DNA and estrogen metabolites on a random sample of 800 participants (400 invasive cases and 400 controls). These 800 women are the target study population of this study. The present proposal seeks funds to conduct NAT2 polymorphism assays on 600 women (funds for the other 200 women were previously obtained from another source). Slow and rapid acetylator genotypic status will be assessed by identifying three variant alleles (which identify 95 % of variants) by PCR-amplification of genomic DNA and digestion by restriction enzymes. Lifetime exposure to both active and passive smoking is already being assessed for all participants as part of the parent study. Association of breast cancer with NAT2 genotypes and effect of cigarette smoking on breast cancer with respect to NAT2 genotypic status will be assessed by fitting unconditional logistic regression models adjusted for potential confounding variables. Statistical interaction between NAT2 genotype and cigarette smoking in breast cancer as well as subgroup analysis with respect to menopausal status, stage and histology of the tumor will also be explored. This study will be able to identify if cigarette smoking is associated with breast cancer risk in a subgroup of women who are predisposed due to inability to detoxify aromatic genes by the NAT2 gene.

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