Dataset Information

Association Between Genetic Polymorphisms in the Promoter Regions of Let-7 and Risk of Papillary Thyroid Carcinoma: A Case-Control Study.

ABSTRACT: The aim of this study was to investigate the association between 2 polymorphisms (ie, rs10877887 and rs13293512) in the promoter regions of let-7 and the risk of papillary thyroid carcinoma (PTC).A case-control study of 618 PTC patients and 562 controls was conducted. The rs10877887 polymorphism was genotyped by using polymerase chain reaction-restriction fragment length polymorphism and the rs13293512 polymorphism was genotyped by using a TaqMan Genotyping Assay. The results were confirmed by DNA sequencing.The rs10877887 polymorphism had reduced risks of PTC in heterozygous comparison, dominant model, and overdominant model (TC vs TT: adjusted odds ratio [OR] = 0.73, 95% confidence interval [95% CI] = 0.58-0.94, P = 0.01; TC/CC vs TT: adjusted OR = 0.79, 95% CI = 0.63-1.00, P = 0.047; TC vs TT/CC: adjusted OR = 0.73, 95% CI = 0.57-0.92, P = 0.007, respectively). Stratified analyses showed that PTC patients carrying the rs10877887 CC genotype were more likely to have multiple tumors (adjusted OR = 1.71, 95% CI = 1.03-2.86, P = 0.04), and PTC patients carrying the rs13293512 TC + CC or CC were more likely to develop N0 status (TC/CC vs TT: adjusted OR = 0.64, 95% CI = 0.43-0.94, P = 0.02; CC vs

Tc/tt

adjusted OR = 0.50, 95% CI = 0.33-0.77, P = 0.001, respectively).Our study suggests that the rs10877887 polymorphism may be associated with the risk of PTC and the rs13293512 polymorphism may correlate to lymph node metastasis in PTC.

SUBMITTER: Wang Y

PROVIDER: S-EPMC4985417 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Association Between Genetic Polymorphisms in the Promoter Regions of Let-7 and Risk of Papillary Thyroid Carcinoma: A Case-Control Study.

Wang Yichao Y Wei Tao T Xiong Junjie J Chen Peng P Wang Xunli X Zhang Lin L Gao Linbo L Zhu Jingqiang J

Medicine 20151001 43

The aim of this study was to investigate the association between 2 polymorphisms (ie, rs10877887 and rs13293512) in the promoter regions of let-7 and the risk of papillary thyroid carcinoma (PTC).A case-control study of 618 PTC patients and 562 controls was conducted. The rs10877887 polymorphism was genotyped by using polymerase chain reaction-restriction fragment length polymorphism and the rs13293512 polymorphism was genotyped by using a TaqMan Genotyping Assay. The results were confirmed by D ...[more]

PMID: 26512603

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Project description:Tumor suppressor p53 directly regulated the abundance of the miR-34b/c. The interaction might contribute to certain cancer. We hypothesized that rs4938723 in the promoter region of pri-miR-34b/c and TP-53 Arg72Pro may be related to the risk of papillary thyroid carcinoma (PTC). A total of 784 patients with PTC and 1006 healthy controls were recruited to participate in this study. The variants were discriminated using a polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). Additionally, the relative expression levels of miR-34b/c and TP-53 in 44 paired samples were revealed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). A significantly increased risk of PTC was observed in the miR-34b/c rs4938723 CT, CC, and CT/CC genotypes compared with the TT genotype (CT vs TT: adjusted odds ratio [OR] = 1.51, 95%confidence interval [CI] = 1.23-1.85; CC vs TT: adjusted OR = 1.89, 95%CI = 1.39-2.63; CT/CC vs TT: adjusted OR = 1.59, 95%CI = 1.30-1.92, respectively). Significantly increased PTC susceptibility was also associated with the TP-53 Arg72Pro CC and CG/CC genotypes compared with the GG genotype (CC vs GG: adjusted OR = 2.04, 95%CI = 1.54-2.70; CG/CC vs GG: adjusted OR = 1.35, 95%CI = 1.11-1.67, respectively). Stratification analysis revealed that patients carrying the TP-53 Arg72Pro C allele and CC genotype had a significantly increased risk for developing N1 (C vs. G: OR = 1.27, 95%CI = 1.03-1.56; CC vs. GG: OR = 1.62, 95%CI = 1.07-2.46, respectively). Combined analysis showed that the genotypes of rs4938723 CT/CC + TP-53CG/CC increased the risk of PTC compared with rs4938723TT + TP-53GG (OR = 2.25, 95%CI = 1.67-3.03). Additionally, level of miR-34b was significantly upregulated in PTC patients.These findings indicate that the miR-34b/c rs4938723 and TP-53 Arg72Pro polymorphisms may contribute to the susceptibility of PTC.

Project description:ObjectivesPapillary thyroid cancer (PTC) is the most common subtype of thyroid cancer, which accounts for 80-90% of all thyroid cancer cases. Though the pathological mechanism hasn't been fully understood, it is reported that both environmental and genetic factor may contribute to the PTC susceptibility. MicroRNAs (miRNAs) are small non-coding RNA molecules which function as the suppressors to participate in a variety of biological processes. Accumulating evidence suggests that polymorphisms of miRNAs were associated with the tumorigenesis of various cancers, including PTC. In this article, we focus on the association between four common microRNA polymorphisms (miR-146a, miR-608, miR-933, and miR-149) and PTC risk in a Han Chinese population.MethodsIn this case-control study, we recruited 1,398 participants in total, including 369 PTC patients, 278 patients with thyroid benign nodules (BN) and 751 normal controls. The miRNAs polymorphisms were genotyped and analyzed by using MALDI-TOF mass spectrometry. The odd ratios and their 95% confidence interval (95% CI) were calculated to evaluate the association between miRNAs polymorphisms and PTC risk. Furthermore, a meta-analysis based on previous studies was conducted to comprehensively assess the diagnostic performance of miR-146a in the PTC diagnosis.ResultsThe miR-146a polymorphisms were shown to be significantly correlated with elevated risk of PTC under the heterozygous, homozygous, dominant and allelic models by comparing the genotype distribution between PTC cases and healthy controls, as well as between PTC cases and BN cases. However, the result of meta-analysis showed no significant association between miR-146a polymorphisms and PTC risk.ConclusionsOur study indicated that the miR-146a polymorphism was significantly associated with PTC risk. In contrast, meta-analysis revealed no evidence of association between miR-146a variants and PTC risk. Further studies are required to elucidate the role of miR-146a in the etiology of PTC.

Dataset Information

Association Between Genetic Polymorphisms in the Promoter Regions of Let-7 and Risk of Papillary Thyroid Carcinoma: A Case-Control Study.

Tc/tt

Publications

Association Between Genetic Polymorphisms in the Promoter Regions of Let-7 and Risk of Papillary Thyroid Carcinoma: A Case-Control Study.

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