Single-nucleotide polymorphism at alcohol dehydrogenase 1B: A susceptible gene marker in oro-/hypopharyngeal cancers from genome-wide association study.

INTRODUCTION: In the era of precision preventive medicine, susceptible genetic markers for oro-/hypopharyngeal squamous cell carcinoma (OPSCC) have been investigated for genome-wide associations. MATERIALS AND METHODS: A case-control study including 659 male head and neck squamous cell carcinoma (HNSCC) patients, including 331 oropharyngeal cancer, treated between March 1996 and December 2016 and 2400 normal controls was performed. A single-nucleotide polymorphism (SNP) array was used to determine genetic loci that increase susceptibility to OPSCC. RESULTS: We analyzed the allele frequencies of 664,994 autosomal SNPs in 659 HNSCC cases; 7 SNPs scattered in loci of chromosomes 5, 7, 9, 11, and 19 were significant in genome-wide association analysis (Pc < 1.0669 × 10-7 ). In OPSCCs (n = 331), two clustered regions in chromosomes 4 and 6 were significantly different from the controls. We successfully identified a missense alteration of the SNP region in alcohol dehydrogenase 1B (ADH1B) (https://genome.ucsc.edu; hg38); the top correlated locus was rs1229984 (p = 1 × 10-11 ). Adjusted for environmental exposure, including smoking, alcohol, and areca quid, a region in chromosome 12, related to alcohol metabolism, was found to independently increase the susceptibility to OPSCC. The ADH1B rs1229984 AA genotype had better overall survival compared to the AG and GG genotypes (p = 0.042) in OPSCC. The GG genotype in rs1229984 was significantly associated with a younger age of onset than other genotypes (p = 0.001 and <0.001, respectively) in OPSCC patients who consumed alcohol. CONCLUSION: ADH1B was an important genetic locus that significantly correlated with the development of OPSCCs and patient survival.

Polygenic Panels Predicting the Susceptibility of Multiple Upper Aerodigestive Tract Cancer in Oral Cancer Patients.

Head and neck cancer was closely related with habitual use of cigarette and alcohol. Those cancer patients are susceptible to develop multiple primary tumors (MPTs). In this study, we utilized the single nucleotide polymorphisms (SNPs) array (Affymetrix Axion Genome-Wide TWB 2.0 Array Plate) to investigate patients' risks of developing multiple primary cancers. We recruited 712 male head and neck cancer patients between Mar 1996 and Feb 2017. Two hundred and eighty-six patients (40.2%) had MPTs and 426 (59.8%) had single cancer. Four hundred and twelve normal controls were also recruited. A list of seventeen factors was extracted and ten factors were demonstrated to increase the risks of multiple primary cancers (alcohol drinking, rs118169127, rs149089400, rs76367287, rs61401220, rs141057871, rs7129229, older age, rs3760265, rs9554264; all were p value < 0.05). Polygenic scoring model was built and the area under curve to predict the risk developing MPTs is 0.906. Alcohol drinking, among the seventeen factors, was the most important risk factor to develop MPT in upper aerodigestive tract (OR: 7.071, 95% C.I.: 2.134-23.434). For those with high score in polygenic model, routine screening of upper digestive tract including laryngoscope and esophagoscope is suggested to detect new primaries early.