The role of meat, meat mutagens, heme iron, and xenobiotic metabolizing genes in neoplasia

Introduction. Meat consumption is increasing globally, and although red and processed meat have been positively associated with neoplasia at various sites, including colon, rectum, and breast, the mechanisms underlying these associations are not well understood. Several meat-related exposures, including heterocyclic amines (HCAs), polycyclic aromatic hydrocarbons (PAHs), heme iron, and nitrate/nitrite, could independently impact carcinogenesis, but epidemiologic research on these exposures is limited.;Methods. This dissertation utilizes detailed meat questionnaires and unique databases to estimate exposure to potentially carcinogenic meat-related exposures and comprises three studies. Study I (Chapter 2) is a cross-sectional analysis of meat, meat cooking methods and doneness levels, HCAs, PAHs, heme iron, and nitrate/nitrite and colorectal adenoma among asymptomatic women in a colonoscopy screening study. Study II (Chapter 3) addresses the interaction between HCAs, PAHs, and nitrate/nitrite and xenobiotic metabolizing enzyme (XME) genes on risk of advanced colorectal adenoma in a nested case-control study. Study III (Chapter 4) prospectively investigates meat and meat-related exposures and breast cancer.;Results. Study I: Red meat, pan-fried meat, and the HCA 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) were positively associated with colorectal adenoma. Using a new heme iron database, there was a suggestive elevated risk of colorectal adenoma with high intake of heme iron. Study II: Variants in several XME genes ( CYP1A1, CYP1B1, CYP3A4, and NQO1) involved in the activation and detoxification of meat-related exposures may modify the association between these exposures and advanced colorectal adenoma. Study III: Red meat, MeIQx, and dietary iron were positively associated with breast cancer and there was a suggestive positive association for heme iron.;Conclusions. In these investigations, both red meat and the HCA MeIQx were positively associated with colorectal adenoma and breast cancer. For advanced colorectal adenoma, there were also suggestive interactions between meat-related exposures and several XME genes. By comprehensively assessing meat intake and utilizing new databases, heme iron was identified as a potential risk factor for both outcomes. Additional investigation into meat-related exposures is necessary to better understand the role of meat in carcinogenesis.