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Comprehensive review of genetic association studies and meta-analyses on miRNA polymorphisms and cancer risk.

ABSTRACT: MicroRNAs (miRNAs) are small RNA molecules that regulate the expression of corresponding messenger RNAs (mRNAs). Variations in the level of expression of distinct miRNAs have been observed in the genesis, progression and prognosis of multiple human malignancies. The present study was aimed to investigate the association between four highly studied miRNA polymorphisms (mir-146a rs2910164, mir-196a2 rs11614913, mir-149 rs2292832 and mir-499 rs3746444) and cancer risk by using a two-sided meta-analytic approach.An updated meta-analysis based on 53 independent case-control studies consisting of 27573 cancer cases and 34791 controls was performed. Odds ratio (OR) and 95% confidence interval (95% CI) were used to investigate the strength of the association.Overall, the pooled analysis showed that mir-196a2 rs11614913 was associated with a decreased cancer risk (OR = 0.846, P = 0.004, TT vs. CC) while other miRNA SNPs showed no association with overall cancer risk. Subgroup analyses based on type of cancer and ethnicity were also performed, and results indicated that there was a strong association between miR-146a rs2910164 and overall cancer risk in Caucasian population under recessive model (OR = 1.274, 95%CI = 1.096-1.481, P = 0.002). Stratified analysis by cancer type also associated mir-196a2 rs11614913 with lung and colorectal cancer at allelic and genotypic level.The present meta-analysis suggests an important role of mir-196a2 rs11614913 polymorphism with overall cancer risk especially in Asian population. Further studies with large sample size are needed to evaluate and confirm this association.

SUBMITTER: Srivastava K

PROVIDER: S-EPMC3511416 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Comprehensive review of genetic association studies and meta-analyses on miRNA polymorphisms and cancer risk.

Srivastava Kshitij K Srivastava Anvesha A

PloS one 20121130 11

<h4>Background</h4>MicroRNAs (miRNAs) are small RNA molecules that regulate the expression of corresponding messenger RNAs (mRNAs). Variations in the level of expression of distinct miRNAs have been observed in the genesis, progression and prognosis of multiple human malignancies. The present study was aimed to investigate the association between four highly studied miRNA polymorphisms (mir-146a rs2910164, mir-196a2 rs11614913, mir-149 rs2292832 and mir-499 rs3746444) and cancer risk by using a ...[more]

PMID: 23226435

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Project description:BackgroundAlthough genetic studies have reported a number of loci associated with cutaneous melanoma (CM) risk, a comprehensive synopsis of genetic association studies published in the field and systematic meta-analysis for all eligible polymorphisms have not been reported.MethodsWe systematically annotated data from all genetic association studies published in the CM field (n = 145), including data from genome-wide association studies (GWAS), and performed random-effects meta-analyses across all eligible polymorphisms on the basis of four or more independent case-control datasets in the main analyses. Supplementary analyses of three available datasets derived from GWAS and GWAS-replication studies were also done. Nominally statistically significant associations between polymorphisms and CM were graded for the strength of epidemiological evidence on the basis of the Human Genome Epidemiology Network Venice criteria. All statistical tests were two-sided.ResultsForty-two polymorphisms across 18 independent loci evaluated in four or more datasets including candidate gene studies and available GWAS data were subjected to meta-analysis. Eight loci were identified in the main meta-analyses as being associated with a risk of CM (P < .05) of which four loci showed a genome-wide statistically significant association (P < 1 × 10(-7)), including 16q24.3 (MC1R), 20q11.22 (MYH7B/PIGU/ASIP), 11q14.3 (TYR), and 5p13.2 (SLC45A2). Grading of the cumulative evidence by the Venice criteria suggested strong epidemiological credibility for all four loci with genome-wide statistical significance and one additional gene at 9p23 (TYRP1). In the supplementary meta-analyses, a locus at 9p21.3 (CDKN2A/MTAP) reached genome-wide statistical significance with CM and had strong epidemiological credibility.ConclusionsTo the best of our knowledge, this is the first comprehensive field synopsis and systematic meta-analysis to identify genes associated with an increased susceptibility to CM.

Project description:ObjectivesReported associations of the cannabinoid receptor 1 (CNR1) single nucleotide polymorphisms (SNPs) with alcohol dependence (AD) have been inconsistent, prompting a meta-analysis to obtain more precise estimates.MethodsA Boolean search of 4 databases (PubMed, Scopus, Google Scholar, and Mednar) sought articles that evaluated the association between CNR1 polymorphisms and risk of AD. We selected the articles with sufficient genotype frequency data to enable calculation of odds ratios (ORs) and 95% confidence intervals (CIs). Using the Population Intervention Comparators Outcome elements, AD patients (P) were compared by genotype data between AD-participants (I) and non-AD-participants (C) in order to determine the risk of AD (O) attributed to the CNR1 SNPs. Analyzing 4 SNPs (rs1049353, rs1535255, rs2023239, and rs806379) using standard genetic models, we examined associations where multiple comparisons were Holm-Bonferroni corrected. The pooled ORs were assessed for aggregate statistical power and robustness (sensitivity analysis). Subgroups were Caucasians and African-Americans.ResultsFrom 32 comparisons, 14 were significant indicating increased risk, from which 5 outcomes (P-value for association [Pa] = .003 to <.001) survived the Holm-Bonferroni-correction, which were deemed robust. In the rs1535255 outcomes, the codominant effect (OR = 1.43, 95% CIs = 1.24-1.65, Pa < .001) had greater statistical power than the dominant effect (OR = 1.30, 95% CI = 1.08-1.57, Pa = .006). In contrast, the rs2023239 codominant outcome was underpowered. Significance of both rs806379 Caucasian outcomes (ORs = 1.20-1.43, 95% CIs = 1.07-1.57, Pa = .003) contrasted with the null effects in African-Americans (ORs = 0.98-1.08, 95% CIs = 0.70-1.53).ConclusionsThree CNR1 SNPs (rs1535255, rs2023239, and rs806379) were implicated in their associations with development of AD: based on aggregate statistical power, rs1535255 presented greater evidence for associations than rs2023239; rs806379 implicated the Caucasian subgroup. Multiple statistical and meta-analytical features (consistency, robustness, and high significance) underpinned the strengths of these outcomes. Our findings could render the CNR1 polymorphisms useful in the clinical genetics of AD.

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Comprehensive review of genetic association studies and meta-analyses on miRNA polymorphisms and cancer risk.

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Comprehensive review of genetic association studies and meta-analyses on miRNA polymorphisms and cancer risk.

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