Impacts of microRNA gene polymorphisms on the susceptibility of environmental factors leading to carcinogenesis in oral cancer

Abstract

Background: MicroRNAs (miRNAs) have been regarded as a critical factor in targeting oncogenes or tumor suppressor genes in tumorigenesis. The genetic predisposition of miRNAs-signaling pathways related to the development of oral squamous cell carcinoma (OSCC) remains unresolved. This study examined the associations of polymorphisms with four miRNAs with the susceptibility and clinicopathological characteristics of OSCC.

Methodology/principal findings: A total of 895 male subjects, including 425 controls and 470 male oral cancer patients, were selected. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and real-time PCR were used to analyze miRNA146a, miRNA196, miRNA499 and miRNA149 genetic polymorphisms between the control group and the case group. This study determined that a significant association of miRNA499 with CC genotype, as compared to the subjects with TT genotype, had a higher risk (AOR = 4.52, 95% CI = 1.24-16.48) of OSCC. Moreover, an impact of those four miRNAs gene polymorphism on the susceptibility of betel nut and tobacco consumption leading to oral cancer was also revealed. We found a protective effect between clinical stage development (AOR = 0.58, 95% CI = 0.36-0.94) and the tumor size growth (AOR = 0.47, 95% CI = 0.28-0.79) in younger patients (age<60).

Conclusions: Our results suggest that genetic polymorphism of miRNA499 is associated with oral carcinogenesis, and the interaction of the miRNAs genetic polymorphism and environmental carcinogens is also related to an increased risk of oral cancer in Taiwanese.

Figure 1. Polymerase chain reaction-restriction fragment length polymorphism of miRNA146a (rs2910164), miRNA196 (rs11614913), miRNA499 (rs3746444) gene.

(A) For miRNA146a rs2910164 gene polymorphism, the wild type homozygous alleles (C/C) yielded a 25 and 122-bp products, the heterozygous alleles (C/G) yielded 25-, 122- and 147-bp products, while the mutated type homozygous alleles (G/G) yielded a 147-bp product. (B) For miRNA196 (rs11614913) gene polymorphism, the wild type homozygous alleles (T/T) yielded a 149-bp product, the heterozygous alleles (C/T) yielded 24-, 125- and 149-bp products, while the mutated type homozygous alleles (C/C) yielded a 24- and 125-bp products (C) For miRNA499 (rs3746444) gene polymorphism, the wild type (T/T) yielded 26- and 120-bp products; the heterozygous alleles (C/T) yielded 26-, 120- and 146-bp products, while the mutated type homozygous alleles (C/C) yielded a 146-bp product.