LAUSR

Multiple primary tumors (MPT), especially in the hypopharynx and esophagus, are challenging in patients with head and neck cancer (HNC). 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 patients with HNC between March 1996 and February 2017. Age- and gender-matched controls were also recruited. A total of 164 patients with HNC 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.