Alcohol Dehydrogenase Polymorphisms Influence Alcohol‐Elimination Rates in a Male Jewish Population

Neumark, Yehuda; Friedlander, Yechiel; Durst, Ronen; Leitersdorf, Eran; Jaffe, Dena H.; Ramchandani, Vijay A.; O’Connor, Sean; Carr, Lucinda G.; Li, T K

doi:10.1097/01.alc.0000108667.79219.4d

Cited by 135 publications

(109 citation statements)

References 21 publications

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“…Extensive exposure to highly toxic, mutagenic and carcinogenic acetaldehyde may be a powerful explanation. 8,9 An investigation carried out among Jewish male has documented that carriers of the ADH1B Arg/Arg genotype have an appreciably lower alcohol removal rate, 35 indicating that ethanol lingers in the body during the slow alcohol oxidation process. Studies performed in Japan have further expressed that male alcoholics with the ADH1B Arg homozygote have greater remaining concentrations of ethanol and acetaldehyde in the saliva and blood when compared with those of other genotypes.…”

Section: Discussionmentioning

confidence: 99%

Genetic modulation of ADH1B and ALDH2 polymorphisms with regard to alcohol and tobacco consumption for younger aged esophageal squamous cell carcinoma diagnosis

Lee¹,

Wu²,

Wu³

et al. 2009

Intl Journal of Cancer

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Genetic variants in alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) genes modulate acetaldehyde removal upon alcohol ingestion. Although these genetic vulnerabilities have been linked to higher esophageal squamous cell carcinoma (ESCC) risks, it is unclear whether they also determine the time of malignancy presentation. The purpose of this investigation was to unravel genotoxic effects of the two alcohol-metabolizing genes with regard to alcohol and tobacco consumption on the age at ESCC diagnosis and tumor dissemination. ADH1B/ALDH2 genotyping was performed on lymphocyte DNA specimens taken from 406 consecutively registered incident patients with pathology-proven ESCC. To fully utilize individual genetic and survival information, survival analyses and gene-longevity applied approaches were introduced. Among heavy drinkers, the ADH1B Arg/Arg (55 years) and ALDH2 Glu/Lys genotypes (54 years) were found to confer a 15 and 16 years earlier carcinoma diagnosed age than His/His and Glu/Glu nondrinkers (both 70 years), respectively. For drinkers, 1-year age advancement was, separately, associated with a 0.977 and 0.953-fold stepwise reduced likelihood of being ADH1B Arg homozygote and ALDH2 Lys variant. Noticeably elevated hazard-ratio (HR) for drinkers of ADH1B slow-form genotype and ALDH2 inactive-form allele were identified in smokers (HR 5 2.3-2.6), but no in nonsmokers. In smokers, appreciably higher cumulative cancer onset risks were correspondingly recognized from the age of 45 and 49 upward among any 1 Lys allele and Arg/Arg 1 Glu/Glu combined-ADH1B/ALDH2-genotype drinkers than nondrinkers. In conclusion, consumption of tobacco and alcohol, coupled with genetic susceptibilities associated with acetaldehyde elimination, as modulated by ADH1B and ALDH2 genotypes, determines a substantial magnitude of tumorigenetic effect on earlier age ESCC diagnosis. ' 2009 UICC Key words: age factor; alcohol drinking; alcohol dehydrogenase; aldehyde dehydrogenase; areca; esophageal neoplasms; smoking Carcinoma stemming from the esophagus ranks as the eighth most common cancer in the world and is one of the deadliest and, yet, most neglected forms of cancer.1 Given the insidious nature of this neoplasm, it has been found that more than 50% of the eventual patients already have unresectable and/or metastatic conditions at the time of tumor presentation.2 Although recent advances in the diagnosis, staging and treatment of esophageal cancer have brought about noteworthy improvement toward some manner of survival, 75% of the patients still die within 1 year of diagnosis, and currently just 5-14% of such patients survive at least 5 years.2,3 Due, in part, to the high case fatality rate, younger esophageal carcinoma onset has been linked to a shorter life expectancy. This leads to a number of challenging health-related issues for the respective family, as well as to substantial work productivity losses for the country.Alcohol intake is a well-recognized determinant for squamous cell carcinoma (SCC) of the esopha...

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Section: Discussionmentioning

confidence: 99%

Genetic modulation of ADH1B and ALDH2 polymorphisms with regard to alcohol and tobacco consumption for younger aged esophageal squamous cell carcinoma diagnosis

Lee¹,

Wu²,

Wu³

et al. 2009

Intl Journal of Cancer

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“…In a more recent study which applied a more refined method for measuring the rate of alcohol degradation, results showed a significant difference in degradation rate according to the ADH1B genotype. 34 In further support of an in vivo effect of the ADH1B genotype is that individuals with the most active enzymes are consistently reported to experience more unpleasant symptoms such as flushing when drinking alcohol compared to individuals with the less active enzymatic forms. [35][36][37][38] Our study had several strengths.…”

Section: Discussionmentioning

confidence: 99%

Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes

et al. 2007

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Alcohol drinking habits and alcoholism are partly genetically determined. Alcohol is degraded primarily by alcohol dehydrogenase (ADH) wherein genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. It is biologically plausible that these variations may be associated with alcohol drinking habits and alcoholism. By genotyping 9080 white men and women from the general population, we found that men and women with ADH1B slow vs fast alcohol degradation drank more alcohol and had a higher risk of everyday drinking, heavy drinking, excessive drinking and of alcoholism. For example, the weekly alcohol intake was 9.8 drinks (95% confidence interval (CI): 9.1-11) among men with the ADH1B Á 1/1 genotype compared to 7.5 drinks (95% CI: 6.4-8.7) among men with the ADH1B Á 1/2 genotype, and the odds ratio (OR) for heavy drinking was 3.1 (95% CI: 1.7-5.7) among men with the ADH1B Á 1/1 genotype compared to men with the ADH1B Á 1/2 genotype. Furthermore, individuals with ADH1C slow vs fast alcohol degradation had a higher risk of heavy and excessive drinking. For example, the OR for heavy drinking was 1.4 (95% CI: 1.1-1.8) among men with the ADH1C Á 1/2 genotype and 1.4 (95% CI: 1.0-1.9) among men with the ADH1B Á 2/2 genotype, compared with men with the ADH1C Á 1/1 genotype. Results for ADH1B and ADH1C genotypes among men and women were similar. Finally, because slow ADH1B alcohol degradation is found in more than 90% of the white population compared to less than 10% of East Asians, the population attributable risk of heavy drinking and alcoholism by ADH1B Á 1/1 genotype was 67 and 62% among the white population compared with 9 and 24% among the East Asian population.

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“…However, since ADH1B genotype and alcohol intake are not independent in our study population, the modifying effect of the ADH1B genotype on breast cancer risk associated with alcohol consumption is overestimated in the case-only analysis, partly due to residual confounding by differences in alcohol consumption caused by the genotype (Albert et al, 2001). Indeed, indications for an association between ADH1B genotype and alcohol consumption, alcoholism or ADH1B genotype, alcohol and breast cancer C Lilla et al adverse reactions such as flushing were observed in previous studies (Whitfield et al, 1998;Borras et al, 2000;Loew et al, 2003;Neumark et al, 2004). There is still controversy in the literature regarding the effect of ADH1B genotype on alcohol pharmacokinetics in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…There is still controversy in the literature regarding the effect of ADH1B genotype on alcohol pharmacokinetics in vivo. Most studies failed to detect differences in blood alcohol or acetaldehyde levels by ADH1B genotype (Yamamoto et al, 1993;Mizoi et al, 1994;Whitfield et al, 2001); only one recent study reported a significantly higher alcohol elimination rate in carriers of the ADH1B*2 allele (Neumark et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Alcohol dehydrogenase 1B (ADH1B) genotype, alcohol consumption and breast cancer risk by age 50 years in a German case–control study

et al. 2005

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Alcohol Dehydrogenase Polymorphisms Influence Alcohol‐Elimination Rates in a Male Jewish Population

Cited by 135 publications

References 21 publications

Genetic modulation of ADH1B and ALDH2 polymorphisms with regard to alcohol and tobacco consumption for younger aged esophageal squamous cell carcinoma diagnosis

Genetic modulation of ADH1B and ALDH2 polymorphisms with regard to alcohol and tobacco consumption for younger aged esophageal squamous cell carcinoma diagnosis

Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes

Alcohol dehydrogenase 1B (ADH1B) genotype, alcohol consumption and breast cancer risk by age 50 years in a German case–control study

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