Dataset Information

3'-UTR Polymorphisms in the MiRNA Machinery Genes DROSHA, DICER1, RAN, and XPO5 Are Associated with Colorectal Cancer Risk in a Korean Population.

ABSTRACT: MicroRNAs play an important role in cancer initiation and development. The aim of this study was to investigate whether polymorphisms in miRNA machinery genes are associated with the development of colorectal cancer (CRC). RAN rs14035 CT heterozygotes and T allele carriers (CT + TT) genotypes had lower risk of CRC, while the DICER1 rs3742330, DROSHA rs10719, and XPO5 rs11077 polymorphisms were not associated with CRC in the full study sample. Specifically, male RAN rs14035 CT heterozygotes and XPO5 rs11077 AA genotype (CT/AA) carriers experienced reduced CRC susceptibility (both colon and rectal). Subgroup analysis demonstrated that the combined RAN rs14035 CT + TT genotype was associated with rectal cancer, but not colon cancer. In addition, the DICER1 rs3742330 AG genotype was associated with a significantly increased risk of colon cancer. Stratified analysis revealed the RAN rs14035 combined CT+TT genotype was associated with decreased CRC risk in male patients without diabetes mellitus (DM) and in patients with rectal cancer. In addition, we found the RAN rs14035 CC genotype was related to a decreased risk of CRC with respect to tumor size and metabolism of homocysteine and folate. Furthermore, patients diagnosed with hypertension or DM who carried the DROSHA rs10719 CC genotype showed increased CRC risk, while the XPO5 rs11077 AC+CC genotype led to increased CRC risk in patients with hypertension only. Our results indicate variations in RAN rs14035, DICER1 rs3742330, XPO5 rs11077, and DROSHA rs10719 of Korean patients are significantly associated with their risk of CRC.

SUBMITTER: Cho SH

PROVIDER: S-EPMC4492935 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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3'-UTR Polymorphisms in the MiRNA Machinery Genes DROSHA, DICER1, RAN, and XPO5 Are Associated with Colorectal Cancer Risk in a Korean Population.

Cho Sung Hwan SH Ko Jung Jae JJ Kim Jung Oh JO Jeon Young Joo YJ Yoo Jung Ki JK Oh Jisu J Oh Doyeun D Kim Jong Woo JW Kim Nam Keun NK

PloS one 20150706 7

MicroRNAs play an important role in cancer initiation and development. The aim of this study was to investigate whether polymorphisms in miRNA machinery genes are associated with the development of colorectal cancer (CRC). RAN rs14035 CT heterozygotes and T allele carriers (CT + TT) genotypes had lower risk of CRC, while the DICER1 rs3742330, DROSHA rs10719, and XPO5 rs11077 polymorphisms were not associated with CRC in the full study sample. Specifically, male RAN rs14035 CT heterozygotes and X ...[more]

PMID: 26147304

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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

3'-UTR Polymorphisms in the MiRNA Machinery Genes DROSHA, DICER1, RAN, and XPO5 Are Associated with Colorectal Cancer Risk in a Korean Population.

Publications

3'-UTR Polymorphisms in the MiRNA Machinery Genes DROSHA, DICER1, RAN, and XPO5 Are Associated with Colorectal Cancer Risk in a Korean Population.

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