EPIDEMIOLOGY OF CARCINOGEN METABOLISM GENES AND RISK OF SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK

Abstract: The risk association between tobacco and alcohol use with squamous cell carcinoma of the head and neck (SCCHN) is well recognized. However, clearly not all individuals who smoke or drink develop SCCHN. Individual genetic susceptibility differen-ces in carcinogen-metabolizing enzyme function, mutagen sensi-tivity, apoptosis, and chromosomal aberrations either alone or in combination have been theorized to modify the risk of SCCHN. Nearly all carcinogens and procarcinogens require activation by metabolizing enzymes. Similarly, detoxifying enzymes exist and deactivate carcinogens as well as their intermediate by-products. Together these enzymes are termed xenobiotic-metabolizing enzymes; genetic polymorphisms of these enzymes can modify an individual’s response to carcinogens and hence the carcino-genic potential of such exposures. In this review, we explore the available evidence in recent literature regarding the risk associa-tion between SCCHN and various xenobiotic-metabolizing enzymes, including cytochrome P450s, glutathione S-transfer-ases, N-acetyltransferases, NAD(P)H:quinone oxidoreductase 1, alcohol dehydrogenase, and aldehyde dehydrogenase. VC 200