Hashibe, M. et al. Evidence for an important role of alcohol- and aldehyde metabolizing genes in cancers of the upper aerodigestive tract. Cancer Epidemiol. Biomarkers Prev. 15, 696-703

Department of Preventive Medicine, Palacký University of Olomouc, Olmütz, Olomoucký, Czech Republic
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 04/2006; 15(4):696-703. DOI: 10.1158/1055-9965.EPI-05-0710
Source: PubMed


Incidence and mortality rates of upper aerodigestive tract cancers in Central Europe are among the highest in the world and have increased substantially in recent years. This increase is likely to be due to patterns of alcohol and tobacco consumption. Genetic susceptibility to upper aerodigestive tract cancer in relation to such exposures is an important aspect that should be investigated among populations in this region.
A multicenter case-control study comprising 811 upper aerodigestive tract cancer cases and 1,083 controls was conducted in: Bucharest (Romania), Lodz (Poland), Moscow (Russia), Banska Bystrika (Slovakia), and Olomouc and Prague (Czech Republic). We analyzed six SNPs in three genes related to ethanol metabolism: alcohol dehydrogenase 1B and 1C (ADH1B, ADH1C) and aldehyde dehydrogenase 2 (ALDH2).
The ADH1B histidine allele at codon 48 was associated with a decreased risk of upper aerodigestive tract cancer; odds ratios (OR) were 0.36 [95% confidence interval (95% CI), 0.17-0.77] for medium/heavy drinkers and 0.57 (95% CI, 0.36-0.91) for never/light drinkers. Moderately increased risks were observed for the ADH1C (350)Val allele (OR, 1.19; 95% CI, 0.98-1.55) and ADH1C (272)Gln allele (OR, 1.24; 95% CI, 0.98-1.55). Medium/heavy drinkers who were heterozygous or homozygous at ALDH2 nucleotide position 248 were at a significantly increased risk of upper aerodigestive tract cancer (OR, 1.76; 95% CI, 1.13-2.75; OR, 5.79; 95% CI, 1.49-22.5, respectively), with a significant dose response for carrying variant alleles (P = 0.0007). Similar results were observed for the ALDH2 +82A>G and ALDH2 -261C>T polymorphisms. When results were analyzed by subsite, strong main effects were observed for squamous cell carcinoma of the esophagus for all six variants. Among the 30% of the population who were carriers of at least one ALDH2 variant, the attributable fraction among carriers (AF(c)) was 24.2% (5.7-38.3%) for all upper aerodigestive tract cancers, increasing to 58.7% (41.2-71.0%) for esophageal cancer. Among carriers who drank alcohol at least thrice to four times a week, the AF(c) for having at least one ALDH2 variant was 49% (21.3-66.8%) for all upper aerodigestive tract cancers, increasing to 68.9% (42.9-83.1%) for esophageal cancer.
Polymorphisms in the ADH1B and ALDH2 genes are associated with upper aerodigestive tract cancer in Central European populations and interact substantially with alcohol consumption.

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    • "Multigenic nature and environmental agents made heterogeneous and complex epidemiology of disease [3]. Different genetic polymorphisms are reported in enzymes involved in the metabolization of alcohol and tobacco greatly increases the risk of Squamous Cell Carcinoma of Head and Neck cancer (SCCHN) [4,5]. Morbidity and prognosis differ from patient to patient depending on causative agents, anatomical site and the stage of disease. "
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    Theoretical Biology and Medical Modelling 06/2013; 10(1). DOI:10.1186/1742-4682-10-38 · 0.95 Impact Factor
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    • "The Journal of Biomedical Research, 2013, 27 both genetic and environmental risk factors contribute to its etiology. Epidemiological studies have demonstrated that tobacco use and alcohol consumption are the most known risk factors for HNC [3] [4] . Furthermore, infection with high-risk types of human papilloma viruses (HPVs) has also been recognized as an increasingly important risk factor for HNC, especially for oropharyngeal squamous cell carcinoma [5] [6] . "
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    ABSTRACT: Although tobacco and alcohol consumption are two common risk factors of head and neck cancer (HNC), other specific etiologic causes, such as viral infection and genetic susceptibility factors, remain to be understood. Human DNA is often damaged by numerous endogenous and exogenous mutagens or carcinogens, and genetic variants in interaction with environmental exposure to these agents may explain interindividual differences in HNC risk. Single nucleotide polymorphisms (SNPs) in genes involved in the DNA damage-repair response are reported to be risk factors for various cancer types, including HNC. Here, we reviewed epidemiological studies that have assessed the associations between HNC risk and SNPs in DNA repair genes involved in base-excision repair, nucleotide-excision repair, mismatch repair, double-strand break repair and direct reversion repair pathways. We found, however, that only a few SNPs in DNA repair genes were found to be associated with significantly increased or decreased risk of HNC, and, in most cases, the effects were moderate, depending upon locus-locus interactions among the risk SNPs in the pathways. We believe that, in the presence of exposure, additional pathway-based analyses of DNA repair genes derived from genome-wide association studies (GWASs) in HNC are needed.
    05/2013; 27(3):179-192. DOI:10.7555/JBR.27.20130034
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    • "For a Mendelian Randomization approach, genetic variants of ALDH2 with a strong influence on alcohol consumption might be more promising and have been successfully applied to study the impact of alcohol consumption on hypertension [39] and esophageal cancer [40]. On the other hand, the principal applicability of ADH gene variants has been demonstrated by recent studies showing that a slow-metabolizing genotype increases the risk of cancers of the upper aerodigestive tract [41], [42]. However, a large fraction of these cancers is believed to be attributable to alcohol consumption [43], making them a promising target to investigate genetically determined differences in ethanol metabolism. "
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