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

Menée à Taïwan auprès de 659 hommes atteints d'un cancer de la tête et du cou et auprès de 659 témoins (durée médiane de suivi : 47,13 mois), cette étude analyse la relation entre des polymorphismes de gènes impliqués dans le métabolisme de l'alcool (ADH1B, ADH1C et ALDH2) et le risque de second cancer primitif, puis identifie des génotypes à haut-risque

Résumé en anglais

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.