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Association between SOD2 V16A variant and urological cancer risk.

ABSTRACT: BACKGROUND:The correlation between superoxide dismutase 2 (SOD2) V16A variant and urological cancer susceptibility has been widely studied, however, with divergent results. RESULTS:Totally, 9,910 cancer patients and 11,239 control subjects were enrolled. V16A variant is associated with an increased susceptibility to urological cancer (A-allele vs. V-allele: OR = 1.06, 95% CI = 1.00 - 1.13, P = 0.047; AA+AV vs. VV: OR = 1.09, 95% CI = 1.02 - 1.16, P = 0.008), especially for prostate cancer (PCa). Serum SOD2 level of PCa patients with VV+VA genotypes was lower than in those with AA genotypes. SOD2 expression is downregulated in both prostate and bladder cancer, as compared to the control. Furthermore, SOD2 was found to be downregulated in more advanced PCa participants, as compared to the ones in early stages. PCa subjects with low SOD2 expression displayed a shorter disease-free survival (DFS) time compared to that of the high SOD2 expression counterparts. CONCLUSIONS:The SOD2 V16A variant may be associated with increased urological cancer susceptibility, especially for prostate cancer. METHODS:A pooled analysis utilizing odds ratios (ORs), in silico tools and ELISA was adopted to demonstrate this association. We also used immunohistochemical staining (IHS) to assess SOD2 expression.

SUBMITTER: Zhang LF

PROVIDER: S-EPMC6977677 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Association between SOD2 V16A variant and urological cancer risk.

Zhang Li-Feng LF Xu Kai K Tang Bo-Wen BW Zhang Wei W Yuan Wei W Yue Chuang C Shi Li L Mi Yuan-Yuan YY Zuo Li L Zhu Li-Jie LJ

Aging 20200112 1

<h4>Background</h4>The correlation between superoxide dismutase 2 (SOD2) V16A variant and urological cancer susceptibility has been widely studied, however, with divergent results.<h4>Results</h4>Totally, 9,910 cancer patients and 11,239 control subjects were enrolled. V16A variant is associated with an increased susceptibility to urological cancer (A-allele vs. V-allele: OR = 1.06, 95% CI = 1.00 - 1.13, <i>P</i> = 0.047; AA+AV vs. VV: OR = 1.09, 95% CI = 1.02 - 1.16, <i>P</i> = 0.008), especial ...[more]

PMID: 31929112

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Project description:Polymorphisms in microRNA (miR) genes and their target sites are a distinct classification of variation in the human genome, which are rapidly being identified and investigated in human cancer. A polymorphism in the miR-196a-2 locus has demonstrated significant associations with various types of cancer, including lung, breast, esophageal and gastric tumors. However, miR-196a-2 has not been fully explored in ovarian cancer, which shares similar biological characteristics with other types of cancer. Therefore, the present study aimed to elucidate the association between a single nucleotide polymorphism (SNP) in the mature sequence of miR-196a-2 (rs11614913, T/C) and the clinical features of 479 Chinese patients with epithelial ovarian cancer (EOC). In addition, the biological significance of this polymorphism was investigated in the OVCAR3 ovarian cancer cell line. Risk association was evaluated in 479 cases of EOC patients and 431 controls. SNPs were analyzed by using polymerase chain reaction based restriction fragment length polymorphism assay. miR-196a expression was evaluated with reverse transcription polymerase chain reaction. The influence of miR-196a-2 rs11614913 T/C on EOC cell migration and invasion ability was further investigated in vitro. The results revealed significant differences in the homozygous CC genotype distribution in patients with EOC (n=479), compared with that of the control subjects (n=431; P=0.026). Analysis of the association between genotype and the risk of EOC revealed that individuals who carried the homozygous CC genotype were 1.34-fold more susceptible to EOC, compared with those carrying the wild-type TT and heterozygous CT genotypes [odds ratio, 1.34; 95% confidence interval, 1.04-2.17; P=0.023]. In addition, the role of this polymorphism in the production of mature miR-196a was investigated. Significantly enhanced production of mature miR-196a was revealed in the C-allelic compared with that of the T-allelic miR-196a-2 precursor (P<0.05). Further examination indicated that miR-196a significantly promoted cell migration and invasion ability in the human OVCAR3 ovarian cell line (P<0.05). In conclusion, the results indicated that the miR-196a-2 rs11614913 CC genotype may increase the risks of ovarian cancer by affecting the expression of mature miR-196a and enhancing cell migration/invasion. The current results provided evidence that the T>C polymorphism in the miR-196a-2 precursor may influence tumorigenesis and metastasis in EOC, and suggested that the functional SNP rs11614913 in the promoter region of pri-miR-196a-2 may be a potential indicator of EOC susceptibility in the population analyzed.

Dataset Information

Association between SOD2 V16A variant and urological cancer risk.

Publications

Association between SOD2 V16A variant and urological cancer risk.

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