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Role of CD152 genetic polymorphisms in the susceptibility to breast cancer.

ABSTRACT: The polymorphisms in cluster of differentiation 152 (CD152) gene have been reported to be associated with breast cancer (BC), but relevant findings were far from conclusive. Therefore, we carried out this meta-analysis to combine those results for a clearer perspective on this issue.In our meta-analysis, a total of 8 eligible publications of 19 case-control studies were selected, which totally contained 7,442 BC cases and 7,376 normal controls. Among the five polymorphisms of CD152 gene, +49 G/A, -1661 A/G and -318 C/T significantly increased the risk of BC under corresponding genetic comparisons; while CT60 G/A polymorphism was negatively related to the cancer susceptibility. In addition, -1772 T/C polymorphism of CD152 gene was not associated with the development of BC.Online databases and other sources were searched for published studies on the relationship between BC susceptibility and CD152 polymorphisms (+49 G/A, -1661 A/G, -1722 T/C, -318 C/T and CT60 G/A). The strength of association was evaluated with pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs). Heterogeneity evaluation was conducted via Q test. Sensitivity analysis was used to detect the stability of our results. Begg's funnel plot and Egger's test were applied to investigate publication bias among selected studies.The polymorphisms +49 G/A, -1661 A/G and -318 C/T may elevate the susceptibility to BC, but the polymorphism CT60 G/A may offer protection against the cancer.

SUBMITTER: Chen H

PROVIDER: S-EPMC5432289 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Role of CD152 genetic polymorphisms in the susceptibility to breast cancer.

Chen Hai H Qi Xiaodong X Bai Xue X Qiu Ping P Chen Bin B

Oncotarget 20170401 16

<h4>Background</h4>The polymorphisms in cluster of differentiation 152 (CD152) gene have been reported to be associated with breast cancer (BC), but relevant findings were far from conclusive. Therefore, we carried out this meta-analysis to combine those results for a clearer perspective on this issue.<h4>Results</h4>In our meta-analysis, a total of 8 eligible publications of 19 case-control studies were selected, which totally contained 7,442 BC cases and 7,376 normal controls. Among the five p ...[more]

PMID: 28416762

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Project description:Continuing advances in genotyping technologies and the inclusion of DNA collection in observational studies have resulted in an increasing number of genetic association studies.To evaluate the overall progress and contribution of candidate gene association studies to current understanding of the genetic susceptibility to cancer.We systematically examined the results of meta-analyses and pooled analyses for genetic polymorphisms and cancer risk published through March 2008.We identified 161 meta-analyses and pooled analyses, encompassing 18 cancer sites and 99 genes. Analyses had to meet the following criteria: include at least 500 cases, have cancer risk as outcome, not be focused on HLA antigen genetic markers, and be published in English.Information on cancer site, gene name, variant, point estimate and 95% confidence interval (CI), allelic frequency, number of studies and cases, tests of study heterogeneity, and publication bias were extracted by 1 investigator and reviewed by other investigators.These 161 analyses evaluated 344 gene-variant cancer associations and included on average 7.3 studies and 3551 cases (range, 508-19 729 cases) per investigated association. The summary odds ratio (OR) for 98 (28%) statistically significant associations (P value <.05) were further evaluated by estimating the false-positive report probability (FPRP) at a given prior probability and statistical power. At a prior probability level of 0.001 and statistical power to detect an OR of 1.5, 13 gene-variant cancer associations remained noteworthy (FPRP <0.2). Assuming a very low prior probability of 0.000001, similar to a probability assumed for a randomly selected single-nucleotide polymorphism in a genome-wide association study, and statistical power to detect an OR of 1.5, 4 associations were considered noteworthy as denoted by an FPRP value <0.2: GSTM1 null and bladder cancer (OR, 1.5; 95% CI, 1.3-1.6; P = 1.9 x 10(-14)), NAT2 slow acetylator and bladder cancer (OR, 1.46; 95% CI, 1.26-1.68; P = 2.5 x 10(-7)), MTHFR C677T and gastric cancer (OR, 1.52; 95% CI, 1.31-1.77; P = 4.9 x 10(-8)), and GSTM1 null and acute leukemia (OR, 1.20; 95% CI, 1.14-1.25; P = 8.6 x 10(-15)). When the OR used to determine statistical power was lowered to 1.2, 2 of the 4 noteworthy associations remained so: GSTM1 null with bladder cancer and acute leukemia.In this review of candidate gene association studies, nearly one-third of gene-variant cancer associations were statistically significant, with variants in genes encoding for metabolizing enzymes among the most consistent and highly significant associations.

Project description:Introduction/objectiveBreast cancer (BC) is the first leading cause of cancer-related mortality in females worldwide. We have investigated the correlation between circ-ITCH gene polymorphisms, circ-ITCH expression, and their effect on β-catenin levels and BC development.MethodsParticipants included 62 BC and 62 controls matched in terms of age. The circ-ITCH polymorphisms rs10485505 and rs4911154 were genotyped using whole blood samples. In addition, mRNA expression analysis of circ-ITCH was performed on BC tissues. The β-catenin levels in serum samples were measured using ELISA.ResultsThe qRT-PCR results demonstrated that circ-ITCH was significantly downregulated in BC compared to normal healthy tissues. The genotype distribution of rs10485505 and rs4911154 were significantly associated with BC risk. For rs10485505, genotype CT and TT were significantly associated with an increased BC risk. In contrast, there was a significant association between rs4911154, genotypes GA and AA, and an increased BC risk. Regarding the rs10485505 genotype, carriers of the T allele frequently have a poor prognosis compared to carriers of the CC genotype. Serum β-catenin in the BC patients' group was significantly higher than in the control group. The relative expression levels of circ-ITCH were remarkably decreased in the BC samples of patients carrying the A allele at rs4911154 compared to patients with a GG genotype. Conversely, β-catenin protein levels were increased in patients carrying the A allele, while rs10485505 genotype carriers of the CT and TT genotypes showed downregulation of circ-ITCH expression fold compared to the CC genotype. Contrarily, β-catenin levels markedly increased in TT and CT genotypes compared with the CC genotype.ConclusionsOur research showed that the rs10485505 polymorphism (T allele) and the rs4911154 polymorphism (A allele) are associated with the risk and prognosis of BC. This finding may be due to the effect on the level of circ-ITCH mRNA expression in BC tissues as well as the level of β-catenin in BC patients.

Dataset Information

Role of CD152 genetic polymorphisms in the susceptibility to breast cancer.

Publications

Role of CD152 genetic polymorphisms in the susceptibility to breast cancer.

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