1256 The Effects of ALDH 2 polymorphisms on pathogenesis and treatment response in malignant melanoma

Background: The incidence of malignant melanoma continues to rise worldwide. While ultraviolet (UV) radiation is a risk factor for melanoma, recent reports have shown link between alcohol consumption and incidence. Alcohol metabolized highly carcinogenic acetaldehyde (AcAH) detoxified by aldehyde dehydrogenase 2 (ALDH2). Therefore, AcAH accumulates when individuals with low ALDH2 activity take alcoholic beverages. We aim determine whether the rs671 polymorphism, which results in hypo-enzymatic activity, impact pathogenesis, prognosis, therapeutic efficacy. Methods: obtained data from three Japanese cohorts: 1) patients histologically diagnosed 2) non-melanoma skin cancer, 3) healthy subjects. determined polymorphism using buccal mucosa samples collected lifestyle information such as intake UV exposure an interview form. Results: analyzed 121 cases. 58 cases were ALDH2*1/*1 (GG, typical homozygote), 52 ALDH2*1/*2 (GA, heterozygote), 11 ALDH2*2/*2 (AA, atypical homozygote). Among them, 60.3% ALDH2*1/*1, 32.7% ALDH2*1/*2, 0% had habitual drinking. 47 treated immune checkpoint inhibitor (ICI) unresectable melanoma. response (complete/partial) rate anti-PD-1 therapy was 61% 90% 50% ALDH2*2/*2. Conclusions: report age, sex, consumption, exposure, frequency ICI. are further analyzing comparing them other cohorts.