Open AccessFAS and FASL variations in outcomes of tobacco- and alcohol-related head and neck squamous cell carcinoma patients
Author(s) -
Ericka Francislaine Dias Costa,
Tathiane Regine Penna Lima,
Leisa LopesAguiar,
Guilherme Nogueira,
Marília Berlofa Visacri,
Júlia C.F. Quintanilha,
Eder de Carvalho Pincinato,
Luciane Calonga,
Fernanda Viviane Mariano,
Albina Altemani,
João Maurício Carrasco Altemani,
Patrícia Moriel,
Carlos Takahiro Chone,
Celso Darío Ramos,
Carmen Sílvia Passos Lima
Publication year - 2020
Publication title -
tumor biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 84
eISSN - 1423-0380
pISSN - 1010-4283
DOI - 10.1177/1010428320938494
Subject(s) - head and neck squamous cell carcinoma , medicine , hazard ratio , oncology , fas ligand , genotype , confidence interval , gastroenterology , proportional hazards model , cisplatin , exact test , head and neck cancer , radiation therapy , apoptosis , chemotherapy , biology , programmed cell death , biochemistry , gene
Radiotherapy and cisplatin lead to cell killing in head and neck squamous cell carcinoma patients, but adverse events and response to treatment are not the same in patients with similar clinicopathological aspects. The aim of this prospective study was to evaluate the roles of TP53 c.215G > C, FAS c.-671A > G, FAS c.-1378G > A, FASL c.-844 C > T, CASP3 c.-1191A > G, and CASP3 c.-182-247G > T single nucleotide variants in toxicity, response rate, and survival of cisplatin chemoradiation-treated head and neck squamous cell carcinoma patients. Genomic DNA was analyzed by polymerase chain reaction for genotyping. Differences between groups of patients were analyzed by chi-square test or Fisher’s exact test, multiple logistic regression analysis, and Cox hazards model. One hundred nine patients with head and neck squamous cell carcinoma were enrolled in study. All patients were smokers and/or alcoholics. Patients with FAS c.-671GG genotype, FAS c.-671AG or GG genotype, and FASL c.-844CC genotype had 5.52 (95% confidence interval (CI): 1.42–21.43), 4.03 (95% CI: 1.51–10.79), and 5.77 (95% CI: 1.23–27.04) more chances of presenting chemoradiation-related anemia of grades 2–4, lymphopenia of grade 3 or 4, and ototoxicity of all grades, respectively, than those with the remaining genotypes. FAS c.-671GG genotype was also seen as an independent predictor of shorter event-free survival (hazard ratio (HR): 2.05; P = 0.007) and overall survival (HR: 1.83; P = 0.02) in our head and neck squamous cell carcinoma patients. These findings present, for the first time, preliminary evidence that inherited abnormalities in apoptosis pathway, related to FAS c.-671A > G and FASL c.-844 C > T single nucleotide variants, can alter toxicity and survival of tobacco- and alcohol-related head and neck squamous cell carcinoma patients homogeneously treated with cisplatin chemoradiation.