Genetic polymorphisms as non-modifiable susceptibility factors to laryngeal cancer

Author:

Escalante Paula1,Barría Tamara2,Cancino Miguel2,Rahal Maritza2,Cerpa Leslie1,Sandoval Christopher1,Molina-Mellico Sebastian1,Suárez Marcelo1,Martínez Matias1,Cáceres Dante Daniel34,Quiñones Luis Abel1,Varela Nelson Miguel1ORCID

Affiliation:

1. Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Department of Basic-Clinical Oncology, Faculty of Medicine, University of Chile, Santiago, Chile & Latin American Network for the Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF-CYTED), Madrid, Spain

2. Otorhinolaryngology Service, Barros Luco Hospital, Santiago, Chile

3. School of Public Health, Faculty of Medicine, University of Chile, Santiago, Chile

4. Health Science Faculty, Tarapacá University, Iquique, Chile

Abstract

Abstract Laryngeal squamous cell carcinoma (LSCC) is a highly disabling disease to the patient, affecting speech, swallowing and respiratory skills. Smoking and alcohol abuse are principal risk factors linked to this disease. Genetic factors can be involved in carcinogenesis by controlling the cell cycle, cell survival, angiogenesis, and invasiveness. Single nucleotide polymorphisms (SNPs) involving specific genes could modulate the risk of LSCC related to known carcinogens by modifying cellular responses, but not all genetic associations are known. In a case–control study, we assess the associations between cyclooxygenase-2 (COX2), epidermal growth factor (EGF), EGF receptor (EGFR), and tumor suppressor P53 SNPs on the risk of LSCC development in the Chilean population. A total of 85 LSCC patients and 95 healthy volunteers were recruited. SNPs genotype were analyzed from genomic DNA by Polymerase Chain Reaction (PCR)-Restriction Fragment Length Polymorphism (RFLP) and associations were estimated by odds ratios (ORs) using unconditional logistic regressions. A significant association between COX2 and TP53 SNP and LSCC risk was found, with an OR = 3.27 for COX2 c.-1329A>G (rs689466) SNP, and an OR = 1.94 for TP53 c.215C>G, Pro72Arg (rs1042522) SNP. These findings suggest that COX2 c.-1329A>G and TP53 c.215C>G (Pro72Arg) SNPs may be risk factors for LSCC. Through this research, we identify two low penetrance genetic variants that may be evaluated as novel biomarkers for this disease, in South American Mestizo populations.

Publisher

Portland Press Ltd.

Subject

Cell Biology,Molecular Biology,Biochemistry,Biophysics

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