Alcohol and aldehyde dehydrogenase polymorphisms and alcoholism

Thomasson, Holly R.; Crabb, David W.; Edenberg, Howard J.; Li, Ting Kai

doi:10.1007/bf01067417

Cited by 382 publications

(497 citation statements)

References 19 publications

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“…The ADH2-2 allele, which encodes the more active b2-subunit, is more prevalent in Asian populations (60 -80%) than Caucasians (0 -10%) (Goedde et al, 1992) and leads to an increased metabolic rate in vitro (9.2 min 71 for b1b1 and 400 min 71 for b2b2 isoenzymes) (Bosron and Li, 1986). Furthermore, the ADH2 polymorphism has been shown to increase the alcohol elimination rate after alcohol consumption (Thomasson et al, 1993) and to influence the metabolism of alcohol in peripheral tissues (Takeshita et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Interaction between alcohol dehydrogenase II gene, alcohol consumption, and risk for breast cancer

et al. 2002

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MaeIII Restriction Fragment Length Polymorphism in exon 3 of the alcohol dehydrogenase II was assessed in serum from 467 randomly selected German women and 278 women with invasive breast cancer to evaluate the interaction between a polymorphism of the alcohol dehydrogenase II gene, alcohol consumption and risk for breast cancer. In both groups, usual consumption of different alcoholic beverages was asked for using semiquantitative food frequency questionnaires. We used multivariable logistic regression to separately estimate the association between alcohol consumption and alcohol dehydrogenase II polymorphism in the population sample and women with breast cancer. The alcohol dehydrogenase II polymorphism was detected in 14 women from the population sample (3.0%) and in 27 women with invasive breast cancer (9.7%). Frequency of alcohol consumption was independent of the genotype in the population sample. In women with breast cancer, there was a significant inverse association between the alcohol dehydrogenase II polymorphism and frequency of alcohol consumption (adjusted case-only odds ratio over increasing frequency of alcohol consumption=0.5; P for interaction=0.02). We observed a gene-environment interaction between the alcohol dehydrogenase II polymorphism, alcohol consumption, and risk for breast cancer. Breast cancer risk associated with alcohol consumption may vary according to the alcohol dehydrogenase II polymorphism, probably due to differences in alcohol metabolism. British Journal of Cancer (2002) (Longnecker, 1994;Smith-Warner et al, 1998;Singletary and Gapstur, 2001;Willett, 2001). Despite growing interest in genetic polymorphisms of the enzymes involved in alcohol metabolism for several diseases associated with alcohol comsumption (Hines et al, 2001;McCarver, 2001; Yamauchi et al, 2001a,b), data regarding the role of these polymorphisms as to the risk for breast cancer are sparse (Freudenheim et al, 1999;Hines et al, 2000). These polymorphisms are good candidates for gene-environment interactions (Millikan et al, 1995), however, because they are likely to influence the most plausible biologic mechanism linking alcohol consumption to risk for breast cancer, i.e. endogenous oestrogens.In humans, alcohol is almost entirely metabolised by oxidative detoxification, mainly dependent on two enzymes, class I alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH). Both enzymes exhibit genetic polymorphisms influencing the rate of conversion from alcohol to acetaldehyde and to acetate (Smith, 1986). The class I ADH isoenzymes are formed by dimeric associations of a, b, and g subunits controlled by three separate gene loci ADH1, ADH2, and ADH3, respectively (Agarwal and Goedde, 1990). Despite recent reports regarding the ADH3 polymorphism and risk for breast cancer (Freudenheim et al, 1999;Hines et al, 2000), nothing is known about the role of the less frequent but metabolically more relevant ADH2 polymorphism and its interaction with alcohol consumption for the risk of breast cancer.The aim of the ...

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Section: Discussionmentioning

confidence: 99%

Interaction between alcohol dehydrogenase II gene, alcohol consumption, and risk for breast cancer

et al. 2002

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“…Its best-known functions are the retinol conversion to retinoic acid and the oxidation of toxic aldehyde metabo¬lites, such as those formed during the alcohol metabolism and certain chemotherapeutic drugs (eg, cyclophosphamide and cisplatin) (Bosron et al, 1988;Thomasson et al, 1991;Visus et al, 2007). In cancer, ALDH+ cells were identified in the breast and the brain (Ginestier et al, 2007;Rasper et al, 2010).…”

Section: Methods Of Identification Of Cancer Stem Cellsmentioning

confidence: 99%

Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma: A Review

Satpute

Hazarey²,

Ahmed³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Research indicates that a small population of cancer cells is highly tumorigenic, endowed with the capacity for self-renewal, and has the ability to differentiate into cells that constitute the bulk of tumors. These cells are considered the ''drivers'' of the tumorigenic process in some tumor types, and have been named cancer stem cells (CSC). Epithelial-mesenchymal transition (EMT) appears to be involved in the process leading to the acquisition of stemness by epithelial tumor cells. Through this process, cells acquire an invasive phenotype that may contribute to tumor recurrence and metastasis. CSC have been identified in human head and neck squamous cell carcinomas (HNSCC) using markers such as CD133 and CD44 expression, and aldehyde dehydrogenase (ALDH) activity. Head and neck cancer stem cells reside primarily in perivascular niches in the invasive fronts where endothelial-cell initiated events contribute to their survival and function. Clinically, CSC enrichment has been shown to be enhanced in recurrent disease, treatment failure and metastasis. CSC represent a novel target of study given their slow growth and innate mechanisms conferring treatment resistance. Further understanding of their unique phenotype may reveal potential molecular targets to improve therapeutic and survival outcomes in patients with HNSCC. Here, we discuss the state-of-the-knowledge on the pathobiology of cancer stem cells, with a focus on the impact of these cells on head and neck tumor progression, metastasis and recurrence due to treatment failure.

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“…These results suggest that ADH variation may affect alcohol use through the mechanism suggested by Thomasson et al (11). They proposed that people with the ADH2*2 or ADH3*1 alleles would metabolise alcohol faster, produce a higher concentration of acetaldehyde, and be more likely to experience either flushing or undefined aversive effects after drinking alcohol.…”

Section: Resultsmentioning

confidence: 62%

Molecular Biology of Alcohol Dependence, a Complex Polygenic Disorder

Whitfield¹,

Nightingale²,

OBrien³

et al. 1998

CCLM

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Alcohol dependence, and the medical conditions which arise from prolonged excessive alcohol use, have no single cause. Like other complex diseases, they result from a combination of social, personal and genetic contributions; but within any society genetic variation has a substantial influence on individual risk. The genes presently known to affect alcohol dependence produce variation in alcohol metabolism; other genes which affect personality or susceptibility to intoxication are likely to be significant but so far reproducible evidence is scanty. Designs which include related subjects have advantages for the study of complex diseases, because any association effects can be placed in the context of overall heritability and because linkage analysis can also be included. Examples of our studies of alcohol metabolism, consumption and dependence are presented.

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Alcohol and aldehyde dehydrogenase polymorphisms and alcoholism

Cited by 382 publications

References 19 publications

Interaction between alcohol dehydrogenase II gene, alcohol consumption, and risk for breast cancer

Interaction between alcohol dehydrogenase II gene, alcohol consumption, and risk for breast cancer

Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma: A Review

Molecular Biology of Alcohol Dependence, a Complex Polygenic Disorder

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