Alcohol dehydrogenase 1B emerged prominent in the carcinogenesis of oro- and hypopharyngeal cancers in Genome-Wide Study in areca-quid endemic area

Head and neck squamous cell carcinomas (HNSqCC) are related with cigarette, alcohol and areca quid (AQ). In the era of precision preventive medicine, susceptible genetic markers for HNSqCCs were investigated by genome-wide association manner. A case-control design and 659 male HNSqCC patients between Mar 1996 and Dec 2016 were recruited with 2400 normal controls. Single nucleotide polymorphisms (SNPs) array (Affymetrix Axion Genome-Wide TWB 2.0 Array Plate) was utilized to investigate patients’ susceptible genetic loci to develop HNSqCCs. Analyzing the allele frequencies of the 664,994 autosomal SNPs from 659 HNSqCCs cases, seven SNPs scattered loci in chr. 5, 7, 9, 11, and 19 reached the threshold of genome-wide significance (Pc < 1.0669 × 10-7). When narrowing into oropharyngeal cancer (n=331), two clustered regions in chr 4 and chr 6 were significantly different from normal population. Imputation successfully identified the missense alteration of SNP region as in ADH1B (https://genome.ucsc.edu, hg38). The top correlated locus is rs1229984 (p = 1x10-11). Further adjusting the exposures of smoking, alcohol drinking and AQ chewing, a region in chr. 12 was identified as independent region for the susceptibility of oropharyngeal cancer and was related with alcohol metabolism. ADH1B rs1229984 AA genotype had better OS compared with AG and GG genotypes (p = 0.042) in oropharyngeal cancer. GG genotype in rs1229984 significantly was occurred younger than other genotypes (p = 0.001 and p < 0.001) in oropharyngeal cancer who drank alcohol.