Laryngeal and oropharyngeal cancer, and alcohol dehydrogenase 3 and glutathione S-transferase M1 polymorphisms

Coutelle, C.; Ward, Patrick; Fleury, Benoît; QUATTROCCHI, P.; Chambrin, H.; Iron, Albert; Couzigou, Patrice; Cassaigne, André

doi:10.1007/s004390050365

Cited by 111 publications

(89 citation statements)

References 40 publications

(45 reference statements)

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“…Another study in France of 21 alcoholic oropharyngeal cancer cases compared to 37 alcoholic controls suggested overall higher OC risk was associated with the ADH 3 1-1 genotype, but this finding was not statistically significant and an alcohol interaction test could not be performed because both cases and controls were heavy alcohol drinkers. 42 Our study in Greece did not exclude subjects with liver damage and in this respect is similar to the Puerto Rico study. Evidence of an ADH 3 SNP interaction with alcohol consumption and OC risk similar to that observed in our study has recently been found in a study of 351 OC cases and 541 controls from western Washington State in the U.S. (S.M.…”

Section: Discussionmentioning

confidence: 59%

Interaction between a single nucleotide polymorphism in the alcohol dehydrogenase 3 gene, alcohol consumption and oral cancer risk

Zavras

Laskaris

et al. 2001

Intl Journal of Cancer

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We investigated effects on oral cancer (OC) risk of an interaction between a single nucleotide polymorphism (SNP) in the alcohol dehydrogenase 3 (ADH 3 ) gene and alcohol consumption levels using a hospital-based study of 93 cases and 99 controls conducted in Athens, Greece. This SNP affects ethanol metabolism in vitro and appeared to interact with alcohol consumption in a previous OC study. We also evaluated a SNP in CYP2E1, another gene involved in ethanol metabolism, reported to be associated with OC risk in a European population. Data on genotypes and risk factors obtained from interviews were analyzed using multivariate logistic regression, accounting for potential confounders. No overall (marginal) association was found between OC risk and ADH 3 genotypes. An interaction between ADH 3 genotypes and alcohol consumption levels, however, was suggested. In non-drinkers, the ADH 3 1-1 genotype has higher risk than ADH 3 1-2 or ADH 3 2-2 genotypes, but for subjects consuming alcohol, lower risk was observed for ADH 3 Many epidemiological studies conducted around the world have documented the strong association between increased risk of oral cancer (OC) and heavy alcohol consumption. [1][2][3][4][5] The mechanism by which alcohol causes OC, however, remains unclear. Questions exist about the importance of consumption patterns, alcohol concentration and other components of different beverages and possible carcinogenic metabolites vs. tissue permeability effects in the mode of action. 6,7 Recent reports strongly implicate the metabolite of ethanol, acetaldehyde, as the main carcinogen in OC. Acetaldehyde has been found to cause mutations, form DNA adducts and inhibit DNA repair. 8 -11 Acetaldehyde levels are regulated primarily by 2 enzymatic systems: alcohol dehydrogenase (ADH) that oxidizes ethanol to acetaldehyde and acetaldehyde dehydrogenase that converts acetaldehyde to acetate. Oxidation of ethanol occurs primarily in the liver, but also in the gastrointestinal tract and oral cavity. [12][13][14][15][16] Seven human genes coding for ADH have been identified to date and 3 of these (ADH1, ADH2 and ADH3) are located in a cluster on chromosome 4. 17,18 Single nucleotide polymorphisms (SNPs) that exhibit different enzymatic properties have been reported for some of these ADH genes. 17,19 -22 For example, it has been shown that cells with the ADH 3 1-1 genotype exhibit a V max for ethanol oxidation that is 2.5-fold higher than that that of the ADH 3 2-2 genotype. 19 Ethanol is also metabolized, to a lesser extent, by CYP2E1 19 and genetic polymorphisms have also been identified for this gene. 23 Because alcohol consumption is a major risk factor for OC, this SNP in ADH 3 is a prime candidate for mediating differences among individuals in OC susceptibility. Evidence of this SNPs interaction with alcohol consumption in OC risk was reported in a case control study conducted in Puerto Rico. 6 By contrast, in a study recently reported using a French population, 24 no association was found with the ADH 3 SNP but an a...

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Section: Discussionmentioning

confidence: 59%

Interaction between a single nucleotide polymorphism in the alcohol dehydrogenase 3 gene, alcohol consumption and oral cancer risk

Zavras

Laskaris

et al. 2001

Intl Journal of Cancer

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“…There may also be an association between the homozygous ADH3*1 genotype and risk of oral cancer (Coutelle et al 1997;Harty et al 1997); however, this gene is not reported to be active in the oral mucosa (Dong et al 1996). Epidemiological evidence points to an increased risk of rectal cancer in heavy drinkers.…”

Section: Alcohol Dehydrogenasementioning

confidence: 99%

Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology

et al. 2004

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Alcohol dehydrogenase (ADH) and mitochondrial aldehyde dehydrogenase (ALDH2) are responsible for metabolizing the bulk of ethanol consumed as part of the diet and their activities contribute to the rate of ethanol elimination from the blood. They are expressed at highest levels in liver, but at lower levels in many tissues. This pathway probably evolved as a detoxification mechanism for environmental alcohols. However, with the consumption of large amounts of ethanol, the oxidation of ethanol can become a major energy source and, particularly in the liver, interferes with the metabolism of other nutrients. Polymorphic variants of the genes for these enzymes encode enzymes with altered kinetic properties. The pathophysiological effects of these variants may be mediated by accumulation of acetaldehyde; high-activity ADH variants are predicted to increase the rate of acetaldehyde generation, while the low-activity ALDH2 variant is associated with an inability to metabolize this compound. The effects of acetaldehyde may be expressed either in the cells generating it, or by delivery of acetaldehyde to various tissues by the bloodstream or even saliva. Inheritance of the high-activity ADH β2, encoded by the ADH2*2 gene, and the inactive ALDH2*2 gene product have been conclusively associated with reduced risk of alcoholism. This association is influenced by gene–environment interactions, such as religion and national origin. The variants have also been studied for association with alcoholic liver disease, cancer, fetal alcohol syndrome, CVD, gout, asthma and clearance of xenobiotics. The strongest correlations found to date have been those between the ALDH2*2 allele and cancers of the oro-pharynx and oesophagus. It will be important to replicate other interesting associations between these variants and other cancers and heart disease, and to determine the biochemical mechanisms underlying the associations.

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“…58 Elevated odds (OR 5.3, 95% CI, 1.0-28.8) of oral cancer in association with the ADH1C*1-1 genotype were observed only among heavy alcohol users (57 drinks per week) in Puerto Rico 59 and among alcoholics in Germany 60 and France. 55,61 However, contradictory conclusions were reported in studies conducted in the U.S. 62,63 and Greece, 64 in which the ''slow metabolizing'' ADH1C*2-2 genotype was associated with increased risk for HNSCC among heavy drinkers. Other studies reported no associations between ADH genotype and risk of HNSCC.…”

Section: Alcohol Consumption and Metabolismmentioning

confidence: 99%

Current topics in the epidemiology of oral cavity and oropharyngeal cancers

2007

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Oral cancer incidence rates rose dramatically during the twentieth century in the United States and Europe, especially among individuals under the age of 60 years. Although influenced by age, sex, and country of origin, incidence trends were most strongly affected by elevated risk among individuals born after approximately 1915. This cohort effect was indicative of strong behavioral influences on oral cancer risk. In this article, associations between oral cancer risk and established behavioral risk factors including alcohol and tobacco use are reviewed. Additionally, possible associations between oral cancer risk and oral hygiene, diet, nutritional status, and sexual behavior as well as the influence of genetic factors on oral cancer risk are considered. Special emphasis is placed on evaluating possible risk differences in individuals above and below the age of 45 and in users and nonusers of alcohol and tobacco. Oral squamous cell carcinomas arise from several anatomic sites within the oral cavity and oropharynx, but most commonly from the oral, mobile tongue.1 In the 1980s, 2 cancer centers in the United States (U.S.) reported an increase in the proportion of incident oral tongue cancers diagnosed in men younger 40 years.2,3 Although absolute numbers had increased, these reports provided no real evidence of rising incidence. Shortly thereafter, however, a significant 2-fold increase in oral tongue cancer mortality rates between 1950 and 1982 was reported in the U.S. for men younger than 30 years. 4 This finding was corroborated by a study in Scotland. 5 Further analysis of the Scottish data revealed that the increase in incidence was not restricted to those younger than 40 but extended to all age groups less than 65 years of age born after 1920-a strong ''cohort effect.'' The cohort effect was indicated by a strong effect of year of birth on oral cancer incidence rates. A flurry of research on global changes in oral cancer incidence was stimulated by these reports.

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Laryngeal and oropharyngeal cancer, and alcohol dehydrogenase 3 and glutathione S-transferase M1 polymorphisms

Cited by 111 publications

References 40 publications

Interaction between a single nucleotide polymorphism in the alcohol dehydrogenase 3 gene, alcohol consumption and oral cancer risk

Interaction between a single nucleotide polymorphism in the alcohol dehydrogenase 3 gene, alcohol consumption and oral cancer risk

Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology

Current topics in the epidemiology of oral cavity and oropharyngeal cancers

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