Association between a Genetic Variant in the hsa-miR-146a Gene and Cancer Risk: An Updated Meta-Analysis.

BACKGROUND AND AIMS: A large number of studies have investigated the association between the potentially functional genetic variant rs2910164 located in the hsa-miR-146a gene and susceptibility to various types of cancer. Nevertheless, the results obtained in these studies are contradictory. Therefore, we conducted a meta-analysis of data from eligible reports comprising a total of 28,359 cases and 41,678 controls. METHODS: The literature included in this meta-analysis was selected from the PubMed database. Quantitative data synthesis was performed by using the OpenMeta-analyst software. RESULTS: The meta-analysis yielded no evidence of an association between rs2910164 and the overall cancer risk. Conversely, the C allele of this genetic variant was found to be associated with a decreased risk of developing bladder and cervical cancer in multiple genetic models. The same direction of association was found for the C allele and liver cancer, gastric cancer and oral squamous cell carcinoma risk. In contrast to these results, the same allelic variant of rs2910164 was found to confer an increased risk of developing lung cancer. The stratified meta-analysis based on ethnicity did not show significant differences in the association between rs2910164 and cancer risk in populations with different ethnic backgrounds. CONCLUSION: We conclude that rs2910164 may represent a valuable biomarker associated with the risk of developing specific types of cancer.

Genetic variants within endothelial nitric oxide synthase gene and prostate cancer: a meta-analysis.

Several variants within gene-encoding endothelial isoform of nitric oxide synthase have been reported to confer prostate cancer (PCa) susceptibility and/or progression. Nevertheless, studies referring to this issue have yielded inconsistent results. In order to elucidate the involvement of these variants in prostate carcinogenesis, we have conducted a meta-analysis of previously published case-control and relevant case-only studies. Eleven studies comprising in total 3,806 cases and 4,466 controls were included in the meta-analysis which yielded evidence of association of rs2070744 (ORCC = 1.43, 95% CI 1.04-1.97; p = 0.03) and intron 4a/b variant (ORab+aa = 1.47, 95% CI 1.00-2.14; p = 0.05) with PCa risk under recessive and dominant model, respectively. Furthermore, PCa patients carrying 4a/b a allele were found to have an increased risk of cancer progression to a less differentiated form, characterized by a high Gleason score (OR = 2.29, 95% CI 1.51-3.49; p < 0.01) and to higher TNM stage (OR = 2.55, 95% CI 1.71-3.81; p < 0.01). These results support the involvement of NOS3 variants in molecular pathogenesis of PCa.

Association between genetic variant in hsa-miR-146a gene and prostate cancer progression: evidence from Serbian population.

PURPOSE: Two previous studies of association between rs2910164 in miR-146a gene and prostate cancer (PCa) risk have provided opposing results. Furthermore, no evidence of association of this SNP with standard prognostic parameters of PCa progression was obtained in mentioned studies. The main aim of this study was to evaluate the possible association between PCa onset and progression to a more aggressive form, since it has not been assessed in a population of European descent. METHODS: In this study, 286 samples of peripheral blood were obtained from patients with PCa, while the control group comprised 199 volunteers derived from general population who gave samples of buccal swabs. For individuals diagnosed with PCa clinicopathological characteristics including serum prostate-specific antigen level at diagnosis, Gleason score (GS), and clinical stage were determined. Genotyping of rs2910164 was performed using Taqman(®) SNP Genotyping Assay. Analysis of SNP association was done using PLINK and SNPStats software. RESULTS: rs2910164 showed no association with PCa risk. Nevertheless, heterozygous genotype was found to be associated with higher GS, as well as with the presence of distant metastases. rs2910164 was also shown to be associated with cancer aggressiveness (p = 0.0067; ORGC = 2.22, 95 %CI 1.24-3.97; ORCC = 0.47, 95 %CI 0.13-1.68). CONCLUSIONS: Our results show no evidence of association between rs2910164 and PCa risk in Serbian population. Conversely, this variant was found to be associated with PCa aggressiveness.

Assessment of association between common variants at 17q12 and prostate cancer risk-evidence from Serbian population and meta--analysis.

This study aimed to evaluate possible association between genotypes and alleles of two 17q12 polymorphisms (rs3760511 and rs7501939) and prostate cancer (PCa) risk and progression. Two hundred seventy-one patients with PCa, 261 patients with benign prostatic hyperplasia (BPH), and 171 controls were included in the study. Single nucleotide polymorphisms (SNPs) were genotyped by using PCR followed by restriction fragment length (PCR-RFLP) analysis. We conducted meta-analysis of published studies regarding association of these SNPs with PCa risk. Evidence of positive association between the AC genotype of the SNP rs3760511 and BPH risk for the best-fitting overdominant model of association (BPH vs. controls comparison, p = 0.026; odds ratio [OR] = 1.58; 95% confidence interval [95%CI] 1.05-2.36) were obtained. The association between T allele of rs7501939 and PCa risk was determined in PCa versus controls comparison (p = 0.0032; OR = 0.66, 95%CI 0.50-0.87) with the best-fitting model of inheritance being log-additive. This variant was also found to be associated with the risk of BPH (p = 0.0023; OR = 0.65, 95%CI 0.49-0.86). We found no association between parameters of PCa progression and the analyzed SNPs. Meta-analysis showed strong association between these variants and PCa risk. Our study shows association between SNPs at locus 17q12 and the risk of prostatic diseases in Serbian population. At the same time, results of meta-analysis suggest the association of these SNPs with PCa risk.

Common variants at 8q24 are associated with prostate cancer risk in Serbian population.

Previous studies have shown correlation between single nucleotide polymorphisms (SNPs) at 8q24 and prostate cancer (PCa) risk. This study aimed to evaluate possible association between genotypes and alleles of 8q24 polymorphisms (rs1447295, rs4242382, rs6983267, rs7017300, and rs7837688) and PCa risk and progression. 150 patients with PCa, 150 patients with benign prostatic hyperplasia (BPH), and 100 healthy controls selected from the general population were recruited for this study. SNPs were genotyped by using PCR-RFLP analysis. There was a significant positive association between the A allele of the SNP rs4242382 and PCa risk [PCa vs. BPH comparison, P = 0.014 for the best-fitting dominant model; odds ratio (OR) =1.98; 95 % confidence interval (95%CI) 1.14-3.43]. We found evidence (P = 0.0064) of association between PCa risk and rs7017300 (heterozygote OR = 1.60; 95%CI 0.95-2.69) when comparing genotype distributions in PCa and BPH patients. The association between T allele rs7837688 and PCa risk was determined in PCa vs. BPH comparison with the best-fitting model of inheritance being log-additive (P = 0.0033; OR = 2.14, 95%CI 1.27-3.61). Odds ratio for carriers of rs6983267 TT genotype under recessive model of association with PCa was found to be 0.36 (PCa vs. control comparison, P = 0.0029; 95%CI 0.19-0.71). For rs1447295, deviation from Hardy-Weinberg equilibrium was observed in BPH patients and controls. We found no association between parameters of PCa progression and five 8q24 SNPs. Locus 8q24 harbors genetic variants associated with PCa risk in Serbian population.

Assessment of possible association between rs3787016 and prostate cancer risk in Serbian population.

Recent study, which included meta-analysis of two genome-wide association studies (GWAS), followed by a replication, identified the association between single nucleotide polymorphism (SNP) rs3787016 at 19p13 and prostate cancer (PCa) risk. Considering possible genetic differences between populations, we conducted the study in order to evaluate the association of this polymorphism with prostate cancer risk in Serbian population. 261 samples of peripheral blood were obtained from the patients with PCa and 257 samples from patients with benign prostatic hyperplasia (BPH). 106 volunteers who gave samples of bucal swabs comprised the control group. For individuals diagnosed with PCa clinicopathological characteristics including serum prostate-specific antigen (PSA) level at diagnosis, Gleason score (GS) and clinical stage were determined. Genotypization of rs3787016 was performed by using Taqman(®) SNP Genotyping Assay. The differences in alelle and genotype frequencies between analyzed groups of subjects were performed by using PLINK, SPSS 17.0 for Windows and SNPStats statistical software. No significant association of rs3787016 with PCa risk was determined comparing allele and genotype frequencies among group of patients diagnosed with PCa and the control group, as well as among groups of patients with PCa and BPH. Also, no evidence of association of rs3787016 with PCa risk was shown using tests for association under dominant and recessive genetic models. SNP rs3787016 showed no significant association with standard prognostic parameters regarding PCa progression, nor with the risk of disease progression assessed according to two different risk classification systems.