Influence ofCASP9c.-1339A>G andCASP3c.-1191A>G variants in outcome of patients with head and neck squamous cell carcinoma

Author(s)

Carvalho, Bruna Fernandes ^[1] ; Costa, Ericka Francislaine Dias ^[1] ; Lopes-Aguiar, Leisa ^[1] ; Liutti, Vitor Teixeira ^[2] ; Leal, Frederico ^[2] ; Vasconcelos, Vivian Castro Antunes ^[2] ; Rinck-Junior, Jose Augusto ^[2] ; Lourenco, Gustavo Jacob ^[1] ; Lima, Carmen Silvia Passos ^{[2, 1]}

Affiliation

^[1] Univ Estadual Campinas, Fac Med Sci, Lab Canc Genet, Campinas - Brazil

^[2] Univ Estadual Campinas, Fac Med Sci, Dept Internal Med, Campinas - Brazil

• Document type: Journal article
• Source: JOURNAL OF ORAL PATHOLOGY & MEDICINE; v. 49, n. 10 SEP 2020.
• Web of Science Citations: 0

Abstract

Background Abnormalities in the intrinsic apoptosis pathway, associated with single nucleotide variants (SNVs) in caspase (CASP) genes, alter head and neck squamous cell carcinoma (HNSCC) proliferation and progression. This prospective study aimed to evaluate whetherCASP9c.-1339A>G andCASP3 c.-1191A>G SNVs influence the outcome of patients with HNSCC. Two hundred sixty-two HNSCC patients were enrolled in the study. Methods DNA and RNA of peripheral blood samples were analyzed using real-time polymerase chain reaction (PCR) for genotyping and quantitative PCR method for gene expression, respectively. Differences inCASP3expressions were analyzed using the Mann-Whitney test. Event-free survival (EFS) and overall survival (OS) were calculated using the Kaplan-Meier curves, log-rank test, and Cox analyses. Results CASP3c.-1191AG or GG genotype was associated with higherCASP3expression when compared with AA genotype (0.50 arbitrary units (AUs) +/- 0.29 standard deviation (SD) vs 0.28 AUs +/- 0.12 SD;P = .02). Patients withCASP9c.-1339GG genotype had 1.54 more chance of presenting disease progression or relapse than patients withCASP9c.-1339AA or AG genotype. Patients withCASP9c.-1339GG andCASP3c.-1191GG combined genotype had 2.64 more chance of presenting progression or relapse of the disease and 2.84 more chance of evolving to death than those with the remaining combined genotypes. Conclusions Our findings provide, for the first time, preliminary evidence that inherited abnormalities in the intrinsic apoptosis pathway, related toCASP9c.-1339A>G andCASP3c.-1191A>G SNVs, act as predictors of HNSCC patients' survival. (AU)

• FAPESP's process: 12/01807-2 - Pharmacogenetics of cisplatin in head and neck squamous cell carcinoma
• Grantee: Carmen Silvia Passos Lima
• Support Opportunities: Regular Research Grants