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Association between ADH1B and ADH1C polymorphisms and the risk of head and neck squamous cell carcinoma

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Tumor Biology

Abstract

Alcohol consumption is one of the major risk factors for head and neck squamous cell carcinoma (HNSCC), and the alcohol dehydrogenase (ADH) family proteins are key enzymes in ethanol metabolism. We examined the associations between single nucleotide polymorphisms (SNPs) of ADH1B and ADH1C and the risk of HNSCC. We analyzed six SNPS of ADH1B, namely −992C > G, −957C > A, +3170A>G, +3377G>T, +3491G>A, and +13543A>G, and five SNPs of ADH1C, namely −1064C>T, −325G>C, +5702A>G, +7462T>C, and +13044A>G, in 260 Korean HNSCC patients and 330 controls, using single base extension and the TaqMan assay. The odds ratios (ORs) and 95 % confidence intervals (95 % CIs) of the CG and GG genotypes of ADH1B −992C>G, the AA genotype of −957C>A, the GG genotype of +3170A>G, the GA genotype of +3491G>A, and +13543A>G were 0.51 (0.32–0.82), 0.63 (0.42–0.94), 1.84 (1.13–2.99), 1.77 (1.15–2.73), 2.34 (1.44–3.79), and 2.21 (1.23–3.95), respectively. The ORs of ADH1C +13044A>G were 1.94 (1.01–3.71) and 1.97 (1.05–3.71) in the dominant and co-dominant models, respectively. The ORs of the GC genotype of ADH1C −325G>C and the AG genotype of +5702A>G were 2.52 (1.51–4.21) and 2.43 (1.36–4.32), respectively. ADH1B +3170A>G and ADH1C +13044A>G were in strong linkage disequilibrium with the other SNPs of ADH1B and ADH1C, respectively. There were gene-environment interactions between ADH1B +3170A>G and ADH1C +13044A>G and alcohol consumption and smoking. ADH1B +3170A>G and ADH1C +13044A>G SNPs are associated with an increased risk of HNSCC, and they could be used as biomarkers for the high-risk group of HNSCC in Koreans.

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References

  1. Tae K, Lee HS, Park BJ, Park CW, Kim KR, Cho HY, et al. Association of DNA repair gene XRCC1 polymorphisms with head and neck cancer in Korean population. Int J Cancer. 2004;222:805–8.

    Article  Google Scholar 

  2. Jeong SW, Tae K, Lee SH, Kim KR, Park CW, Park BL, et al. Cox-2 and IL-10 polymorphisms and association with squamous cell carcinoma of the head and neck in a Korean sample. J Korean Med Sci. 2010;25:1024–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Ji YB, Tae K, Lee YS, Lee SH, Kim KR, Park CW, et al. XPD polymorphisms and risk of squamous cell carcinoma of the head and neck in a Korean sample. Clin Exp Otorhinolaryngol. 2010;3:42–7.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Blot WJ, McLaughlin JK, Winn DM, Austin DF, Greenberg RS, Preston-Martin S, et al. Smoking and drinking in relation to oral and phayngeal cancer. Cancer Res. 1988;48:3282–7.

    CAS  PubMed  Google Scholar 

  5. IARC. Alcoholic consumption and ethyl carbamate. In: IARC monographs on the evaluation of carcinogenic risks to humans. Lyon, France: IARC; 2010, vol. 96.

  6. Obe G, Jonas R, Schmidt S. Metabolism of ethanol in vitro produces a compound which induces sister-chromatid exchanges in human peripheral lymphocytes in vitro: acetaldehyde not ethanol is mutagenetic. Mutat Res. 1986;174:47–51.

    Article  CAS  PubMed  Google Scholar 

  7. Fang JL, Vaca CE. Detection of DNA adducts of acetaldehyde in peripheral white blood cells of alcohol abusers. Carcinogenesis. 1997;18:627–32.

    Article  CAS  PubMed  Google Scholar 

  8. Homann N, Jousimies-Somer H, Jokelainen K, Heine R. Salaspuro M High acetaldehyde levels in saliva after ethanol consumption: methodological aspects and pathogenetic implication. Carcinogenesis. 1997;18:1739–43.

    Article  CAS  PubMed  Google Scholar 

  9. Harada S, Misawa S, Agarwal DP, Goedde HW. Liver alcohol dehydrogenase and aldehyde dehydrogenase in the Japanese: isoenzyme variation and its possible role in alcohol intoxication. Am J Hum Genet. 1980;32:8–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Edenberg HJ. The genetics of alcohol metabolism-role of alcohol dehydrogenase and aldehyde dehydrogenase variants. Alcohol Res Health. 2007;30:5–13.

    PubMed  PubMed Central  Google Scholar 

  11. Ji YB, Tae K, Ahn TH, Lee SH, Kim KR, Park CW, et al. ADH1B and ALDH2 polymorphisms and their associations with increased risk of squamous cell carcinoma of the head and neck in the Korean population. Oral Oncol. 2011;47:583–7.

    Article  CAS  PubMed  Google Scholar 

  12. Yokoyama A, Muramatsu T, Omori T, Yokoyama T, Matsushita S, Higuchi S, et al. Alcohol and aldehyde dehydrogenase gene polymorphisms and oropharyngolaryngeal, esophageal and stomach cancers in Japanese alcoholics. Carcinogenesis. 2001;22:433–9.

    Article  CAS  PubMed  Google Scholar 

  13. Hiraki A, Matsuo K, Wakai K, Suzuki T, Hasegawa Y, Tajima K. Gene–gene and gene–environment interactions between alcohol drinking habit and polymorphisms in alcohol-metabolizing enzyme genes and the risk of head and neck cancer in Japan. Cancer Sci. 2007;98:1087–91.

    Article  CAS  PubMed  Google Scholar 

  14. Guo H, Zhang G, Mai R. Alcohol dehydrogenase-1B Arg47His polymorphism and upper aerodigestive tract cancer risk: a meta-analysis including 24,252 subjects. Alcohol Clin Exp Res. 2012;36:272–8.

    Article  CAS  PubMed  Google Scholar 

  15. Chang JS, Straif K, Guha N. The role of alcohol dehydrogenase genes in head and neck cancers: a systematic review and meta-analysis of ADH1B and ADH1C. Mutagenesis. 2012;27:275–86.

    Article  CAS  PubMed  Google Scholar 

  16. Hashibe M, Boffetta P, Zaridze D, Shangina O, Szeszenia-Dabrowska N, Mates D, et al. Evidence for an important role of alcohol- and aldehyde-metabolizing genes in cancers of the upper aerodigestive tract. Cancer Epidemiol Biomarkers Prev. 2006;15:696–703.

    Article  CAS  PubMed  Google Scholar 

  17. Zhang L, Jiang Y, Wu Q, Li Q, Chen D, Xu L, et al. Gene-environment interaction on the risk of esophageal cancer among Asian poppulations with the G48A polymorphism in the alcohol dehydrogenase-2 gene: a meta-analysis. Tumor Biol. 2014;35:4705–17.

    Article  CAS  Google Scholar 

  18. Dura P, Berkers T, van Veen EM, Salomon J, te Morsche RH, Kristinsson JO, et al. Polymorphisms in alcohol-metabolizing enzymes and esophageal carcinoma susceptibility: a Dutch Caucasian case-control study. J Hum Genet. 2013;58(11):742–8.

    Article  CAS  PubMed  Google Scholar 

  19. Risch A, Ramroth H, Raedts V, Rajaee-Behbahani N, Schmezer P, Bartsch H, et al. Laryngeal cancer risk in Caucasians is associated with alcohol and tobacco consumption but not modified by genetic polymorphisms in class I alcohol dehydrogenases ADH1B and ADH1C, and glutathione-S-transferases GSTM1 and GSTT1. Pharmacogenetics. 2003;13:225–30.

    Article  CAS  PubMed  Google Scholar 

  20. Harty LC, Caporaso NE, Hayes RB, Winn DM, Bravo-Otero E, Blot WJ, et al. Alcohol dehydrogenase 3 genotype and risk of oral cavity and pharyngeal cancers. J Natl Cancer Inst. 1997;89:1698–705.

    Article  CAS  PubMed  Google Scholar 

  21. Visapää JP, Götte K, Benesova M, Li J, Homann N, Conradt C, et al. Increased cancer risk in heavy drinkers with the alcohol dehydrogenase 1C*1 allele, possibly due to salivary acetaldehyde. Gut. 2004;53:871–6.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Muto M, Takahashi M, Ohtsu A, Ebihara S, Yoshida S, Esumi H. Risk of multiple squamous cell carcinomas both in the esophagus and the head and neck region. Carcinogenesis. 2005;26:1008–12.

    Article  CAS  PubMed  Google Scholar 

  23. Wang D, Ritchie JM, Smith EM, Zhang Z, Turek LP, Haugen TH. Alcohol dehydrogenase 3 and risk of squamous cell carcinomas of the head and neck. Cancer Epidemiol Biomarkers Prev. 2005;14:626–32.

    Article  CAS  PubMed  Google Scholar 

  24. Cadoni G, Boccia S, Petrelli L, Di Giannantonio P, Arzani D, Giorgio A, et al. A review of genetic epidemiology of head and neck cancer related to polymorphisms in metabolic genes, cell cycle control and alcohol metabolism. Acta Otorhinolaryngol Ital. 2012;32:1–11.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Hiyama T, Yoshihara M, Tanaka S, Chayama K. Genetic polymorphisms and head and neck cancer risk (Review). Int J Oncol. 2008;32:945–73.

    CAS  PubMed  Google Scholar 

  26. Sturgis EM, Dahlstrom KR, Guan Y, Eicher SA, Strom SS, Spitz MR, et al. Alcohol dehydrogenase 3 genotype is not associated with risk of squamous cell carcinoma of the oral cavity and pharynx. Cancer Epidemiol Biomarkers Prev. 2001;10:273–5.

    CAS  PubMed  Google Scholar 

  27. Osier MV, Pakstis AJ, Soodyall H, Comas D, Goldman D, Odunsi A, et al. A global perspective on genetic variation at the ADH genes reveals unusual patterns of linkage disequilibrium and diversity. Am J Hum Genet. 2002;71:84–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Brennan P, Lewis S, Hashibe M, Bell DA, Boffetta P, Bouchardy C, et al. Pooled analysis of alcohol dehydrogenase genotypes and head and neck cancer: a HuGE review. Am J Epidemiol. 2004;159:1–16.

    Article  PubMed  Google Scholar 

  29. Lee HC, Lee HS, Jung SH, Yi SY, Jung HK, Yoon JH, et al. Association between polymorphisms of ethanol-metabolizing enzymes and susceptibility to alcoholic cirrhosis in a Korean male population. J Korean Med Sci. 2001;16:745–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Jung SH, Lee HC, Yoon JH, Lee HS, Kim CY. The association between genetic polymorphisms of ethanol-metabolizing enzymes and susceptibility to alcoholic liver cirrhosis. Korean J Hepatol. 1998;4:1–11.

    Google Scholar 

  31. Höög JO, Hedén LO, Larsson K, Jörnvall H, von Bahr-Lindström H. The gamma 1 and gamma 2 subunits of human liver alcohol dehydrogenase. cDNA structures, two amino acid replacements, and compatibility with changes in the enzymatic properties. Eur J Biochem. 1986;159:215–8.

    Article  PubMed  Google Scholar 

  32. Packer BR, Yeager M, Burdett L, Welch R, Beerman M, Qi L, et al. SNP500Cancer: a public resource for sequence validation, assay development, and frequency analysis for genetic variation in candidate genes. Nucleic Acids Res. 2006;1(34):D617–21.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 133-792, South Korea

    Yong Bae Ji, Seung Hwan Lee, Kyung Rae Kim, Chul Won Park, Chang Myeon Song & Kyung Tae

  2. Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul, South Korea

    Byung Lae Park & Hyoung Doo Shin

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  1. Yong Bae Ji
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Ji, Y.B., Lee, S.H., Kim, K.R. et al. Association between ADH1B and ADH1C polymorphisms and the risk of head and neck squamous cell carcinoma. Tumor Biol. 36, 4387–4396 (2015). https://doi.org/10.1007/s13277-015-3078-y

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  • DOI: https://doi.org/10.1007/s13277-015-3078-y

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