Investigative Role of Pre-MicroRNAs in Bladder Cancer Patients: A Case–Control Study in North India

Abstract

MicroRNAs (miRNA) are a class of small noncoding RNA molecules that have been implicated in a wide variety of cellular functions through post-transcriptional regulations on target genes. Common genetic variants (single-nucleotide polymorphisms, SNPs) in pre-miRNA genes may alter their expression and/or maturation effecting thousands of target mRNAs, resulting in varied functional consequences. Three common SNPs (hsa-mir-146a G>C rs2910164, hsa-mir-196a2 C>T rs11614913, and hsa-mir-499 T>C rs3746444) in pre-miRNAs were investigated to evaluate their association with urinary bladder cancer risk. The hospital-based case-control study comprised of 212 histologically confirmed patients with urinary bladder cancer and 250 healthy controls who were unrelated, of similar ethnicity, and age and gender matched. Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism methodology. Our results showed that the heterozygous genotype of rs11614913 was higher in cases than controls but the results were marginally significant (p = 0.055; odds ratio, 1.44). Smoking had no impact in modulating the effect of any of the three miRNA SNPs studied. No association was observed with either the tumor stage or grade in patients with bladder cancer. Even though there was no association between the individuals carrying the variant genotypes of the three miRNA studied and bladder cancer risk, marginal significance of heterozygousity in rs11614913 suggested further characterization of miRNA SNPs in a large cohort of varied ethnicity. This could further provide new prospects for understanding the underlying mechanisms between miRNAs and disease etiology.

Meta-analysis confirms that a common G/C variant in the pre-miR-146a gene contributes to cancer susceptibility and that ethnicity, gender and smoking status are risk factors

“…As shown in Figure 2, the G-allele of rs2910164 had a higher representation in cases and controls of Caucasian populations (75.07 and 76.58%, respectively) than in those of Asian populations (50.42 and 47.88%, respectively). The distribution of all the genotypes in the controls was consistent with the HWE in all studies, except for 3 studies (Catucci et al, 2010;George et al, 2011;Mittal et al, 2011). Several studies collected information on possible confounding factors, such as smoking status (Guo et al, 2010;Xu et al, 2010;Zeng et al, 2010) and gender (Xu et al, 2008;Zeng et al, 2010;Akkiz et al, 2011), and the gene-environment interaction effect was ana-, and the gene-environment interaction effect was anaand the gene-environment interaction effect was analyzed in subgroups.…”

“…The study selection process is shown in Figure 1. Finally, 22 articles (Jazdzewski et al, 2008;Xu et al, 2008;Hoffman et al, 2009;Hu et al, 2009;Tian et al, 2009;Catucci et al, 2010;Guo et al, 2010;Liu et al, 2010;Okubo et al, 2010;Pastrello et al, 2010;Srivastava et al, 2010;Xu et al, 2010;Zeng et al, 2010;Garcia et al, 2011;George et al, 2011;Akkiz et al, 2011;Hishida et al, 2011;Mittal et al, 2011;Permuth-Wey et al, 2011;Yue et al, 2011;Zhou et al, 2011;Zhou et al, 2012) with 11,901 cases and 14,200 controls were included in the present meta-analysis. An article by Catucci et al (2010) reported a case-control study of a German population and an Italian population separately, and one by Jazdzewski et al (2008) reported studies on populations of Finland, Poland, and USA separately.…”

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

“…There were fifteen studies of caucasian descent and twenty-four studies of Asian descent. The genotype distributions in the controls of fourteen studies were not conforming to HWE (p<0.05) (Okubo et al, 2010;Akkiz et al, 2011;Ling et al, 2011;Mittal et al, 2011;Zhou et al, 2011;Xiang et al, 2012;Shan et al, 2013;Vinci et al, 2013;Wei et al, 2013;Zou and Zhao, 2013;Bansal et al, 2014;Ma et al, 2014;Omrani et al, 2014;Wang et al, 2014).…”

“…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 ...…”

miR-196a2 polymorphisms and susceptibility to cancer: A meta-analysis involving 24,697 subjects

“…During the reading of the 25 full-text manuscripts, 4 studies were excluded due to incomplete rs11614913 polymorphism distribution data required for OR calculation (10)(11)(12)(13). For the remaining 21 records, baseline characteristics of the patients and control subjects were summarized, the study quality was assessed, HWE in particular was assessed by Chi-square test; two records involving Indian populations published in 2011 were excluded for disagreement with HWE (P<0.05) (14,15), thus leaving 19 articles identified with criteria for inclusion and exclusion (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). All studies were case-control studies.…”