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.

Lack of Association between Hsa-Mir-499 rs3746444 Polymorphism and Cancer Risk: Meta-analysis Findings

“…One study was excluded as it was not associated with hsa-mir-499 rs3746444 A>G (Kupcinskas et al, 2012). After further excluding two abstracts (Hu et al, 2009;Hwang et al, 2010), thirty-nine case-control studies involving 14,136 cases and 16,937 controls were selected for meta-analysis (Hu et al, 2009;Tian et al, 2009;Catucci et al, 2010;Liu et al, 2010;Okubo et al, 2010;Srivastava et al, 2010;Akkiz et al, 2011;George et al, 2011;Ling et al, 2011;Mittal et al, 2011;Vinci et al, 2011;Zhou et al, 2011;Alshatwi et al, 2012;Chu et al, 2012;Kim et al, 2012;Min et al, 2012;Xiang et al, 2012;Zhou et al, 2012;Ahn et al, 2013;Lv et al, 2013;Shan et al, 2013;Song et al, 2013;Umar et al, 2013;Vinci et al, 2013;Wei et al, 2013;Wu et al, 2013;Zou and Zhao, 2013;Bansal et al, 2014;Chu et al, 2014;Du et al, 2014;Gutierrez-Camino et al, 2014;Hasani et al, 2014;Hou et al, 2014;Hu et al, 2014;Ma et al, 2014;Omrani et al, 2014;Pu et ...…”

A Genetic Variant in MiR-146a Modifies Digestive System Cancer Risk: a Meta-analysis

“…In accordance with the inclusion criteria, 21 eligible studies including 20 published (Xu et al, 2008;Zeng et al, 2010;Okubo et al, 2010;Srivastava et al, 2010;Guo et al, 2010;Akkız et al, 2011;Zhang et al, 2011;Ahn et al, 2012;Chu et al, 2012;Hezova et al, 2012;Mihalache et al, 2012;Xiang et al, 2012;Zhou et al, 2012;Zhou et al, 2012;Min et al, 2012;Kim et al, 2012;Chae et al, 2013;Hu et al, 2013;Lv et al, 2013;Ma et al, 2013;Pavlakis et al, 2013;Wei et al, 2013) and 1 unpublished were collected in this work, with 9,558 cases and 10,614 controls. Two study identified by manually searching reference list of retrieved studies were included (Chu et al, 2012;Kim et al, 2012).…”

“…Two study identified by manually searching reference list of retrieved studies were included (Chu et al, 2012;Kim et al, 2012). The Figure 1.…”

“…In recent years, a lot of studies including case-control studies and meta-analyses have been conducted to determine the association between genetic variants in the precursor or mature miRNA sequence of miR-146a and multiple kinds of digestive system cancers at various sites, such as oral cancer (Chu et al, 2012), esophagus cancer (Guo et al, 2010;Wei et al, 2013), pancreatic cancer (Pavlakis et al, 2013), colorectal cancer (Hezova et al, 2012;Min et al, 2012;Lv et al, 2013;Ma et al, 2013), cholangicarcinoma (Mihalache et al, 2012), gallbladder cancer (Srivastava et al, 2010), gastric cancer (Okubo et al, 2010;Zeng et al, 2010;Ahn et al, 2012;Zhou et al, 2012), and liver cancer (Xu et al, 2008;Akkız et al, 2011;Zhang et al, 2011;Kim et al, 2012;Xiang et al, 2012;Zhou et al, 2012), etc. However, the results are conflicting and inconclusive.…”

Impact of microRNA dynamics on cancer hallmarks: An oral cancer scenario

“…76 Furthermore, there was a significant association between SNPs of these four miRNA genes and an increased risk of OSCC associated with betel nut chewers and smokers. 77 As the genes encoding miRNAs are frequently located in fragile sites, it is plausible that loss or gain of chromosomal material could alter miRNA expression. 78 For instance, the expression of miR-100 and miR-125b, two miRNAs mapping to chromosome 11q, is significantly decreased in OSCC owing to the loss of chromosome material.…”