Tag single nucleotide polymorphisms of alcohol-metabolizing enzymes modify the risk of upper aerodigestive tract cancers: HapMap database analysis

Authors

  • C.-S. Chung,

    1. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
    2. Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
    3. Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
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  • Y.-C. Lee,

    1. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
    2. Division of Biostatistics, Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan
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  • J.-M. Liou,

    1. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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  • C.-P. Wang,

    1. Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan
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  • J.-Y. Ko,

    1. Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan
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  • J.-M. Lee,

    1. Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
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  • M.-S. Wu,

    Corresponding author
    1. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
    • Address correspondence to: Professor Ming-Shiang Wu, MD, PhD, and Professor Hsiu-Po Wang, MD, Department of Internal Medicine, College of Medicine, National Taiwan University, 7, Chung-Shan South Road, Taipei 100, Taiwan. Email: mingshiang@ntu.edu.tw; wanghp@ntu.edu.tw

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  • H.-P. Wang

    Corresponding author
    1. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
    • Address correspondence to: Professor Ming-Shiang Wu, MD, PhD, and Professor Hsiu-Po Wang, MD, Department of Internal Medicine, College of Medicine, National Taiwan University, 7, Chung-Shan South Road, Taipei 100, Taiwan. Email: mingshiang@ntu.edu.tw; wanghp@ntu.edu.tw

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  • Authors' contribution: Design of the study: Chen-Shuan Chung, Yi-Chia Lee, Ming-Shiang Wu, Hsiu-Po Wang; Provision of the study materials: Yi-Chia Lee, Jyh-Ming Liou, Chen-Ping Wang, Jenq-Yuh Ko, Jang-Ming Lee, Hsiu-Po Wang; Analysis and interpretation of data: Chen-Shuan Chung, Yi-Chia Lee, Ming-Shiang Wu; Drafting of the manuscript: Chen-Shuan Chung, Yi-Chia Lee, Ming-Shiang Wu; Final approval of the article: All authors.

Summary

Although alcohol is associated with higher upper aerodigestive tract (UADT) cancer risk, only a small fraction of alcoholics develop cancers. There is a lack of evidence proving the association of tag single nucleotide polymorphisms of alcohol-metabolizing enzymes with cancer risk. The aim of this study was to determine the association of these genetic polymorphisms with UADT cancer risk in a Chinese population. It was a hospital-based case–control candidate gene study. The databases of the International HapMap Project were searched for haplotype tag single nucleotide polymorphisms of the genes alcohol dehydrogenase (ADH)1B, ADH1C, and aldehyde dehydrogenase (ALDH)2. The genotyping was performed by the Sequenom MassARRAY system. Totally, 120 head and neck squamous cell carcinoma, 138 esophageal squamous cell carcinoma patients, and 276 age- and gender-matched subjects were enrolled between June 2008 and June 2010.Minor alleles of ADH1B (rs1229984) and ALDH2(rs671) were not only associated with the risk of UADT cancers (odds ratio [OR] [95% confidence interval, CI]: 3.53 [2.14–5.80] and 2.59 [1.79–3.75], respectively) but also potentiated the carcinogenic effects of alcohol (OR [95% CI]: 53.44 [25.21–113.29] and 70.08 [33.65–145.95], respectively). Similar effects were observed for head/neck and esophageal cancer subgroups. Multivariate logistic regression analysis identified four significant risk factors, including habitual use of cigarettes, alcohol, betel quid, and lower body mass index (P < 0.001). The haplotypes GAGC (OR 1.61, 95% CI 1.08–2.40, P = 0.018) and CCAATG (OR 1.69, 95% CI 1.24–2.30, P < 0.001) on chromosomes 4 and 12, respectively, were associated with higher cancer risk. These findings suggested that risk allele or haplotype carriers who consume alcohol and other carcinogens should be advised to undergo endoscopy screening. The information can be used to determine the degree of susceptibility of each subject and can be combined with other environmental factors, like carcinogen consumption, in the screening analysis.

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