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

Abstract

BackgroundOral 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.Methodology/Principal findingsWe 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.ConclusionsIn 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.

Impact of Aurora Kinase A Polymorphism and Epithelial Growth Factor Receptor Mutations on the Clinicopathological Characteristics of Lung Adenocarcinoma

“…For instance, AURKA contributes to higher tumor grades in estrogen receptor-positive primary breast cancers [ 34 ]. Moreover, the coexistence of betel nut chewing and AURKA SNPs is associated with the development of oral squamous cell carcinoma [ 16 ]. Regarding the relationship between AURKA and EGFR, a previous study revealed higher AURKA activity in patients with LADC resistance to tyrosine kinase inhibitors that target EGFR mutations [ 19 ].…”

“…Four AURKA SNPs, namely rs1047972 (C/T), rs2273535 (T/A), rs6024836 (A/G), and rs2064863 (T/G), were selected due to their considerable effects on other malignancies [ 16 , 17 , 18 ]. Regarding genotyping, DNA was first extracted from the leukocytes of venous blood samples from each participant using the QIAamp DNA kits (Qiagen, Valencia, Valencia, CA, USA) according to the manufacturer’s instructions.…”

“…Aurora kinase A (AURKA) is a protein that regulates centromere and cell mitosis, affecting the progression of several neoplasms [ 15 , 16 , 17 , 18 ]. AURKA SNPs reduce the risk of large tumors in patients with hepatocellular carcinoma [ 18 ] and are protective factors against urothelial cell carcinoma [ 17 ].…”

Molecular Markers of Anticancer Drug Resistance in Head and Neck Squamous Cell Carcinoma: A Literature Review

“…Furthermore, the upregulation of AurkA leads to abnormal centrosome numbers and the induction of aneuploidy [ 62 , 63 , 64 ]. This overexpression is associated with HNSCC and promotes cell proliferation, tumor progression, and metastasis [ 65 ]. Previous reports showed that the EGFR and AurkA protein levels were elevated in tumor tissue, which represents a risk group with a poor disease-free survival [ 66 ].…”

Impact of the Receptor for Advanced Glycation End Products Genetic Polymorphisms on the Progression in Uterine Cervical Cancer

“…Genetic polymorphisms are probably related to the development and occurrence of certain diseases, such as cancer. Genetic variants may affect the promoter activity and gene expression 16 - 19 . SNPs have a modifying function on genetic expression and are related to an increased risk of ovarian and breast tumorigenesis 20 .…”