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Association of Wilms' tumor 1 gene single-nucleotide polymorphism rs16754 with colorectal cancer.

ABSTRACT: Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide. Our recent study demonstrated that the expression of Wilms' tumor 1 gene (WT1) is associated with surgical outcome in CRC patients. The present study aimed to investigate the genetic association of the single-nucleotide polymorphism rs16754 in the WT1 gene with the occurrence of CRC, using an age-matched case-control study design. In addition, the correlation between genotype and WT1 expression was investigated. Genomic DNA samples from 104 CRC cases, aged 15-65 years, and 208 healthy controls, were genotyped for rs16754 using the TaqMan genotyping method. The genotype distribution conformed to the Hardy-Weinberg equilibrium (P=0.80). The overall minor allele frequency (MAF) of rs16754 (allele A) was 0.33. The MAF among CRC cases was significantly higher compared with that in controls (0.39 vs. 0.31, respectively; P=0.03). The AA genotype was significantly associated with the disease (odds ratio = 2.51, 95% confidence interval: 1.24-5.07, P=0.01). Cases with the AA genotype exhibited a significantly poorer 3-year overall survival (60%), compared with those with the GG or GA genotypes (80%) (log-rank test, P<0.01). Reverse transcription quantitative polymerase chain reaction analysis demonstrated that the expression of WT1 in tumor tissues was higher compared with that in normal tissue; however, there were no significant differences in its expression among different genotypes. Therefore, rs16754 was found to be associated with the occurrence and prognosis of CRC in our subjects.

SUBMITTER: Sangkhathat S

PROVIDER: S-EPMC4665320 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Association of Wilms' tumor 1 gene single-nucleotide polymorphism rs16754 with colorectal cancer.

Sangkhathat Surasak S Maneechay Wanwisa W Chaiyapan Welawee W Kanngern Samornmas S Boonpipattanapong Teeranut T

Molecular and clinical oncology 20150916 6

Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide. Our recent study demonstrated that the expression of Wilms' tumor 1 gene (WT1) is associated with surgical outcome in CRC patients. The present study aimed to investigate the genetic association of the single-nucleotide polymorphism rs16754 in the WT1 gene with the occurrence of CRC, using an age-matched case-control study design. In addition, the correlation between genotype and WT1 ...[more]

PMID: 26807256

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Project description:The Wilms tumor-1 (WT1) protein is an important regulator of malignant hematopoiesis and has been implicated in the pathogenesis of acute myeloid leukemia (AML). Recently special attention has been paid to the relationship of the WT1 single nucleotide polymorphism (SNP) rs16754 with AML risk and outcome, but the conflicting results made it difficult to draw definitive conclusions. In the present study, we systematically reviewed the literature and performed a meta-analysis of existing evidence. We searched Embase, Pubmed, Web of Science, Medline, Cochrane Library, Wanfang, and China National Knowledge Infrastructure databases using predefined search methodology for relevant studies. We pooled odd ratio (OR) with 95% confidence intervals (95% CI) to evaluate the association between SNP rs16754 and AML risk. In addition, we analyzed hazard ratio (HR) with 95% CI for overall survive, relapse-free survival, and disease-free survival. Q-statistic was used to assess the homogeneity and Egger test was used to evaluate publication bias. Eleven studies met the inclusion criteria for analysis. The results of fixed-effect meta-analyses revealed no association between SNP rs16754 and AML risk (AA + GA vs GG: OR = 0.92, 95% CI: 0.71-1.19, P = .518; AA vs GA + GG: OR = 1.23, 95% CI: 0.86-1.76, P = .262; AA vs GG: OR = 1.05, 95% CI: 0.68-1.63, P = .820; AG vs AA: OR = 0.77, 95% CI: 0.53-1.13, P = .186; AG vs GG: OR = 0.89, 95% CI: 0.68-1.16, P = .376). In subgroup analysis by race, age, and disease type, we did not find any significant association. However, the presence of rs16754 GA/GG genotype was associated with improved overall survive (HR = 0.48, 95% CI: 0.26-0.91, P = .024) and relapse-free survival (HR = 0.82, 95% CI: 0.68-1.00, P = .048) compared with the rs16754 AA. In summary, the WT1 SNP rs16754 was not associated with AML risk, but it had a significant impact on clinical outcome in AML patients.

Dataset Information

Association of Wilms' tumor 1 gene single-nucleotide polymorphism rs16754 with colorectal cancer.

Publications

Association of Wilms' tumor 1 gene single-nucleotide polymorphism rs16754 with colorectal cancer.

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