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 differences in carcinogen-metabolizing enzyme function, mutagen sensitivity, 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 carcinogenic potential of such exposures. In this review, we explore the available evidence in recent literature regarding the risk association between SCCHN and various xenobiotic-metabolizing enzymes, including cytochrome P450s, glutathione S-transferases, N-acetyltransferases, NAD(P)H:quinone oxidoreductase 1, alcohol dehydrogenase, and aldehyde dehydrogenase.

Involvement of Single-Nucleotide Polymorphisms in Predisposition to Head and Neck Cancer in Saudi Arabia

“…Genetic predisposition to head and neck cancer is a contributing factor to smoking, environmental and occupational exposures, and interaction with oncogenenic viral infections (Siemiatycki et al, 2004;Hashibe et al, 2007;Ho et al, 2007;Chung and Gillison, 2009). In this association study, we investigated the role of 10 polymorphisms in genes involved in cell cycle and DNA repair pathways as risk factors for head and neck cancer occurrence (Fig.…”

“…In addition, human papillomavirus infection has been correlated with some groups of squamous cell carcinoma of the head and neck (HNSCC), particularly in the oropharynx (Chung and Gillison, 2009). Further, genetic variations in genes implicated in cell cycle regulation, DNA repair, apoptosis, and other cellular processes play important roles in the etiology of HNSCC (Ho et al, 2007).…”

Head and Neck Squamous Cell Carcinoma: Prognosis using molecular approach

“…A wide variety of DNA repair systems and xenobiotic metabolizing enzymes (XMEs) have arisen through the evolutionary process to maintain genomic integrity. Ironically, defects in these pathways have been implicated in causing excessive cell death or transformation of cells, resulting in increased risk of HNSCC [5,6]. Polymorphisms in DNA repair genes such as XPA (Xeroderma Pigmentosum Complementation group A) [7,8], XPC (Xeroderma Pigmentosum Complementation group C) [9,10], XPD (Xeroderma Pigmentosum Complementation group D) [11,12], XRCC1 (X-Ray Cross Complementing group 1) [13,14], XRCC3 (X-Ray Cross Complementing group 3) [15,16] and Phase II xenobiotic metabolizing genes such as Glutathione S-transferases (GSTs: M1, T1 and P1) have been reported in the pathophysiology of HNSCC [1,2,17].…”

Sequence Variants of NAT1 and NAT2 and Other Xenometabolic Genes and Risk of Lung and Aerodigestive Tract Cancers in Central Europe

“…The mutagenic chemical carcinogens in tobacco smoke are eliminated from the human body via a series of enzymes that metabolize the carcinogenic compounds. Genetic variation in functionally important regions of xenometabolic genes seem to influence the rate of action of these enzymes (2)(3)(4). An individual's genetic profile of xenometabolic alleles will have a role in determining the rate at which carcinogens are eliminated and therefore the extent of carcinogen exposure.…”

“…An individual's genetic profile of xenometabolic alleles will have a role in determining the rate at which carcinogens are eliminated and therefore the extent of carcinogen exposure. Individuals who have inherited alleles that result in higher degree of carcinogen exposure are expected to have a higher cancer risk relative to those who inherited lower exposure alleles (2)(3)(4)(5)(6).…”