Combined effect of genetic polymorphisms of AURKA and environmental factors on oral cancer development in Taiwan

• Published in: PLOS ONE Vol. 12; no. 2; p. e0171583
• Main Authors: Chou, Chia-Hsuan, Chou, Ying-Erh, Chuang, Chun-Yi, Yang, Shun-Fa, Lin, Chiao-Wen
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science (PLoS) 02.02.2017; Public Library of Science
• Subjects: Alcohol use; Analysis; Areca; Areca - adverse effects; Aurora Kinase A; Aurora Kinase A - genetics; Biology and Life Sciences; Breast cancer; Cancer; Carcinoma, Squamous Cell; Carcinoma, Squamous Cell - etiology; Carcinoma, Squamous Cell - genetics; Case-Control Studies; Chewing; Confidence intervals; Disease susceptibility; Ecological risk assessment; Environmental aspects; Environmental factors; Environmental risk; Gene Frequency; Gene Frequency - genetics; Genetic polymorphisms; Genetic Predisposition to Disease; Genetic Predisposition to Disease - genetics; Haplotypes; Health risk assessment; Health risks; Humans; Male; Mastication; Medical research; Medicine; Medicine and Health Sciences; Middle Aged; Mouth cancer; Mouth Neoplasms; Mouth Neoplasms - etiology; Mouth Neoplasms - genetics; Mutation; Oral cancer; Oral squamous cell carcinoma; Patients; Polymerase chain reaction; Polymorphism; Polymorphism, Single Nucleotide; Polymorphism, Single Nucleotide - genetics; Protein-serine/threonine kinase; Q; R; Real-Time Polymerase Chain Reaction; Research Article; Risk analysis; Risk Factors; Risk management; Science; Single-nucleotide polymorphism; Smoking; Smoking - adverse effects; Squamous cell carcinoma; Taiwan; Taiwan - epidemiology; Threonine; Tumorigenesis; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0171583

Oral squamous cell carcinoma (OSCC) is the sixth and fourth most common cause of cancer death in men worldwide and in Taiwan, respectively. AURKA, which encodes a centrosome-related serine/threonine kinase, is frequently amplified and overexpressed in many human cancers, particularly advanced OSCC. We conducted a hospital-based case-control study to estimate AURKA single-nucleotide polymorphisms (SNPs) and environmental risk factors to determine OSCC susceptibility and clinicopathological characteristics. We enrolled a total of 876 OSCC patients and 1200 controls. Four SNPs of AURKA, namely rs1047972, rs2273535, rs2064863, and rs6024836, were analyzed using real-time polymerase chain reaction (PCR). Among the 1420 smokers, the AURKA polymorphism carriers with the betel nut chewing habit had a higher risk of oral cancer than AURKA wild-type (WT) carriers without the betel nut chewing habit. Patients with the AURKA rs2064863 gene had a 1.365-fold higher risk of stage III or IV OSCC (95% confidence interval [CI] 1.029-1.811) than those with the rs2064863 WT gene. Furthermore, carriers of the AURKA rs1047972/rs2273535/rs2064863 C-A-T haplotype had a 1.736-fold (95% CI 1.110-2.715) higher risk of OSCC than controls (C-T-T, the most common haplotype). Among patients with the betel quid chewing habit, carriers of other haplotypes (C-T-T, C-A-G, T-A-T, T-A-G, T-T-T, and C-T-G) had a 12.857-fold (95% CI 10.731-15.404) increased risk, and carriers of the C-A-T haplotype had the highest risk (AOR: 31.120; 95% CI 13.864-69.850) of OSCC, compared with those without the betel quid chewing who harbored other haplotypes. In conclusion, betel nut chewing combined with the AURKA C-A-T haplotypes lead to a high risk of OSCC. These findings reveal a novel genetic-environmental predisposition for oral tumorigenesis.