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Association of microRNA biosynthesis genes XPO5 and RAN polymorphisms with cancer susceptibility: Bayesian hierarchical meta-analysis.

ABSTRACT: XPO5/RAN-GTP complex mediates the nuclear transport of pre-miRNAs in the miRNA processing system, its altered expression is indicated to be correlated with cancer risk. Several studies have inspected the association between XPO5 or RAN polymorphisms and the risk of various cancers, but the findings remain controversial. A Bayesian hierarchical meta-analysis was carried out to review and analyze the effect of XPO5 and RAN polymorphisms on cancer risk. The association was estimated by calculating the logarithm of odds ratio (Log OR) and 95% credible interval (95% CrI). The expression quantitative trait loci (eQTL) analysis was used for in silico functional validation of the identified significant susceptibility loci. Consequently, 38 case-control studies (from 27 citations) with 27,459 cancer cases and 25,151controls were included in the meta-analysis of the five most prevalent SNPs (rs11077 A/C, rs2257082 G/A, rs3803012 A/G, rs14035 C/T, rs3809142 C/T). In the XPO5 gene rs11077 SNP, the minor C allele significantly increased the risk of cancer (Log OR = 0.120, 95% CrI = 0.013, 0.241), and a strong association between rs11077 SNP and cancer risk was also found in the dominant model (CC + AC vs. AA: Log OR = 0.132, 95% CrI = 0.009, 0.275). In addition, the minor GG genotype allele of the RAN gene rs3803012 SNP significantly increased the cancer risk (Log OR = 0.707, 95% CrI = 0.059, 1.385). Statistically significant associations between rs3803012 SNP and cancer risk were also observed in the recessive model (GG vs. AG + AA: Log OR = 0.708, 95% CrI = 0.059, 1.359). Furthermore, the eQTL analysis revealed that rs11077 SNP was significantly correlated with XPO5 mRNA expression, which provided additional biological basis for the observed positive association. Our results suggest that XPO5 rs11077 may be a possible functional susceptibility locus for cancer risk.

SUBMITTER: Shao Y

PROVIDER: S-EPMC7052917 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Association of microRNA biosynthesis genes XPO5 and RAN polymorphisms with cancer susceptibility: Bayesian hierarchical meta-analysis.

Shao Yi Y Shen Yi Y Zhao Lei L Guo Xudong X Niu Chen C Liu Fen F

Journal of Cancer 20200203 8

XPO5/RAN-GTP complex mediates the nuclear transport of pre-miRNAs in the miRNA processing system, its altered expression is indicated to be correlated with cancer risk. Several studies have inspected the association between XPO5 or RAN polymorphisms and the risk of various cancers, but the findings remain controversial. A Bayesian hierarchical meta-analysis was carried out to review and analyze the effect of XPO5 and RAN polymorphisms on cancer risk. The association was estimated by calculating ...[more]

PMID: 32127945

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Project description:BackgroundMicroRNA (miRNA) processing machinery gene variant was associated with several diseases. We aimed to explore for the first time the association of machinery gene (DROSHA rs10719A/G; DICER1 rs3742330A/G; RAN rs14035C/T; and XPO5 rs11077T/G) variants with the susceptibility and phenotype of end-stage renal disease (ESRD).MethodA total of 281 participants (98 ESRD patients and 183 healthy volunteers) were enrolled. Real-Time TaqMan allelic discrimination assay was applied for the genotyping of the specified variants. Multiple logistic regression models, univariate, multivariate, and principal component analyses were carried out.ResultsCarrying one DICER1 rs3742330*G allele conferred protection against developing ESRD [heterozygote comparison: OR = 0.30, 95% CI = 0.15-0.62, dominant model: OR = 0.35, 95% CI = 0.17-0.70]. Similarly, for XPO5 rs11077T/G, homozygote and heterozygote carriers of G variant were less likely to develop ESRD [homozygote comparison: adjusted OR = 0.23, 95% CI = 0.11-0.50, and heterozygote comparison: OR = 0.50, 95% CI = 0.22-0.92, and allelic model: OR = 0.46, 95% CI = 0.34-0.70]. RAN rs14035*TT subjects were 5 times more likely to develop ESRD while being heterozygote (CT) have twice the risk [homozygote comparison: 5.18, 95% CI = 2.28-11.8, heterozygote comparison: OR = 2.12, 95% CI = 1.10-409]. Subgroup analysis also detected DICER1 rs3742330*A, XPO5 rs11077*T, and RAN rs14035*T as genetic risk determinants for ESRD development in both sex and age categories. Two genotype combinations of DROSHA/DICER1/XPO5/RAN were associated with increased susceptibility to ESRD [A-A-T-T: OR = 9.49, 95%CI = 2.48-36.31 (P = .001) and G-A-T-T: OR = 5.92, 95%CI = 1.77-19.83 (P = .004), respectively].ConclusionVariants and combined genotypes of DICER1 rs3742330, XPO5 rs11077, and RAN rs14035 might be associated with ESRD development in the study population. Integrating molecular analysis in ESRD risk stratification is warranted.

Dataset Information

Association of microRNA biosynthesis genes XPO5 and RAN polymorphisms with cancer susceptibility: Bayesian hierarchical meta-analysis.

Publications

Association of microRNA biosynthesis genes XPO5 and RAN polymorphisms with cancer susceptibility: Bayesian hierarchical meta-analysis.

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