Alcohol Metabolizing Enzymes Gene Polymorphisms and Susceptibility to Multiple Head and Neck Cancers.

Research paper by Huei-Tzu HT Chien, Chi-Kuang CK Young, Tzu-Ping TP Chen, Chun-Ta CT Liao, Hung-Ming HM Wang, Sou-De SD Cheng, Shiang-Fu SF Huang

Indexed on: 09 Mar '19Published on: 08 Mar '19Published in: Cancer prevention research (Philadelphia, Pa.)


Multiple primary tumors (MPTs), especially in the hypopharynx and esophagus, are challenging in head and neck cancer (HNC) patients. Alcohol and alcohol-metabolizing genes were reported to be related to upper digestive tract cancers. Here, we investigated whether the genotypes of alcohol-metabolizing enzymes (ADH1B, ADH1C and ALDH2) affected patients' susceptibility to developing MPTs. We recruited 659 male HNC patients between March 1996 and February 2017. Age and gender-matched controls were also recruited. One hundred sixty-four HNC patients were identified to have second or third malignancies. The single-nucleotide polymorphisms in ADH1B (rs1229984), ADH1C (rs698) and ALDH2 (rs671) were analyzed by TaqMan assays. The prevalence of ALDH2 *2 allele carriers is significantly higher than that of *1*1 homozygotes for oral cavity (p = 0.013) and oropharyngeal cancers (p = 0.012). For ADH1B, the number of *1 allele carriers is significantly higher than that of *2*2 homozygotes for oropharyngeal (p = 0.017) and hypopharyngeal cancers (p < 0.001). ADH1C (rs698) SNPs are not significantly associated with tumor subsites (all p > 0.05). Polymorphisms in ALDH2 (*2 allele carriers) and ADH1B (*1 allele carriers) significantly increase the risk of developing MPTs in the upper digestive tract (p < 0.001, OR [95% confidence interval, CI]: 5.186 [2.444-11.004] and p < 0.05, OR [95% CI]: 2.093 [1.149-3.812], respectively). ALDH2 (rs671) *2 and ADH1B (rs1229984) *1 allele carriers were shown to develop MPTs in the upper digestive tract. Genetic information may be used to identify high-risk patients for the development of MPTs. Copyright ©2019, American Association for Cancer Research.

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