Polymorphism of the insulin gene is associated with increased prostate cancer risk.
Ontology highlight
ABSTRACT:
SUBMITTER: Ho GY
PROVIDER: S-EPMC2377060 | biostudies-other | 2003 Jan
REPOSITORIES: biostudies-other
Similar Datasets
Project description:BackgroundThe purpose of this study was to evaluate the role of osteoprotegerin gene (OPG) polymorphisms as genetic modifiers in the etiology of prostate cancer (PCa) and disease progression.MethodsThree hundred and sixty one patients with PCa and 195 normal controls were enrolled in the study, and two genetic polymorphisms, 149 T/C and 950 T/C in the putative promoter region of OPG, were genotyped.ResultsThere was no significant difference in the genotype frequencies between PCa patients and controls (P = 0.939 and 0.294 for 149 T/C and 950 T/C polymorphisms, respectively). However, those patients with TC and TT genotypes in the 950 T/C polymorphism had a significantly increased risk of extraprostatic (age-adjusted odds ratio; aOR = 1.74 and 2.03 for TC and TT genotypes compared with the CC genotype, P = 0.028) and metastatic disease (aOR = 1.72 and 2.76 for TC and TT genotypes compared with the CC genotype, P = 0.009) compared with those with the CC genotype. In addition, analysis of the metastatic PCa patients (Stage D) showed that the presence of the T allele of the OPG 950 T/C polymorphism was an independent risk factor predicting survival by Cox proportional hazard regression analyses (P = 0.031).ConclusionProgression of PCa may be influenced by an intrinsic genetic factor of the host's bone metabolism. The variant C allele of 950 T/C in the OPG promoter may play a major role as a genetic safe guard against progression in patients with PCa.
| S-EPMC2527333 | biostudies-literature
Project description:We investigated single nucleotide polymorphism (SNP) of the betaglycan gene (TGFBR3) encoding the TGFβ co-receptor in endometrial cancer (EC) and its association with betaglycan expression. The study group included 153 women diagnosed with EC and 248 cancer-free controls. SNP genotyping and gene expression were analyzed using TaqMan probes. Three out of the eight SNPs tested, i.e., rs12566180 (CT; OR = 2.22; 95% CI = 1.15-4.30; p = 0.0177), rs6680463 (GC; OR = 2.34; 95% CI = 1.20-4.53; p = 0.0120) and rs2296621 (TT; OR = 6.40; 95% CI = 1.18-34.84; p = 0.0317) were found to be significantly associated with increased risk of EC (adjusted to age, body mass index, menarche and parity). Among the analyzed SNPs, only rs2296621 demonstrated the impact on the increased cancer aggressiveness evaluated by the WHO grading system (G3 vs. G1/2, GT-OR = 4.04; 95% CI = 1.56-10.51; p = 0.0026; T-OR = 2.38; 95% CI = 1.16-4.85; p = 0.0151). Linkage disequilibrium (LD) analysis revealed high LD (r2 ≥ 0.8) in two haploblocks, constructed by rs2770186/rs12141128 and rs12566180/rs6680463, respectively. In the case of C/C haplotype (OR = 4.82; 95% CI = 1.54-15.07; p = 0.0116-Bonferroni corrected) and T/G haplotype (OR = 3.25; 95% CI = 1.29-8.15; p = 0.0328-Bonferroni corrected) in haploblock rs12566180/rs6680463, significantly higher frequency was observed in patients with EC as compared to the control group. The genotype-phenotype studies showed that SNPs of the TGFBR3 gene associated with an increased risk of EC, i.e., rs12566180 and rs2296621 may affect betaglycan expression at the transcriptomic level (rs12566180-CC vs. TT, p < 0.01; rs2296621-GG vs. TT, p < 0.001, GT vs. TT, p < 0.05). Functional consequences of evaluated TGFBR3 gene SNPs were supported by RegulomeDB search. In conclusion, polymorphism of the TGFBR3 gene may be associated with an increased EC occurrence, as well as may be the molecular mechanism responsible for observed betaglycan down-regulation in EC patients.
| S-EPMC7650668 | biostudies-literature
Project description:Numerous studies have uncovered the association of Interleukin-10 (IL-10) gene rs1800896 polymorphism with the risk of prostate cancer (PCa); however, their conclusions were inconsistent. Therefore, we conducted this meta-analysis to evaluate the role of IL-10 rs1800896 polymorphism in the risk of PCa. 16 eligible studies in 15 articles involving 6,301 cases and 6,510 controls were identified by researching PubMed, Google, CNKI, and EMBASE up to April 1, 2017. Our results revealed that IL-10 rs1800896 polymorphism was associated with the decreased risk of PCa under the homozygous model. Subgroup analysis by ethnicity revealed that rs1800896 polymorphism decreased the risk of PCa among Caucasians. In conclusion, IL-10 gene rs1800896 polymorphism is associated with the decreased risk of PCa. Larger studies with more diverse ethnic populations are needed to confirm these results.
| S-EPMC5630404 | biostudies-literature
Project description:Introduction: The HPGD gene was associated with some cancers, such as colorectal, breast, prostate, and bladder. However, detailed role of 15-hydroxyprostaglandin dehydrogenase (HPGD) gene remain unclear in prostate cancer. The study was to investigate the correlation between rs8752 that located in the 3'untranslated region (UTR) of the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene and prostate cancer (PCa) risk. Materials and Methods: 109 patients from the First Affiliate Hospital of Soochow University were recruited. According to the results of pathologic diagnosis, all patients were divided into two groups (prostate cancer and benign prostatic hyperplasia). The single-nucleotide polymorphism (SNP) rs8752 was genotyped in all samples by direct sequencing. Results: 54 prostate cancer and 55 BPH patients were included with a median age of 70.41 and 67.62 years, respectively. No statistically significant difference between two groups in patient criteria. The frequency of the GG homozygote and AG+GG genotype were 37.74% and 62.26% in 54 prostate cancer samples, while in 55BPH patients, values were 62.50% and 37.50%. Compared with the GG genotype, the combined GA+AA genotypes had a significantly higher risk of prostate cancer (OR = 2.750; 95% CI: 1.266-5.971, p = 0.011). Furthermore, the risk effect was obtained in subgroups of PCa patient group, the AA+AG genotypes significantly associated with the higher Gleason score samples (AA+AG vs GG: OR = 3.50, 95%CI = 1.106-11.072, p = 0.033) and the risk of pathological stage (AA+AG vs GG: OR = 4.00, 95%CI = 1.253-12.767, p = 0.019). Conclusions: rs8752 in the 3'untranslated region (UTR) of the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene was found to be responsible for the susceptibility to prostate cancer in Chinese individuals.
| S-EPMC5706011 | biostudies-literature
Project description:PurposeThe mismatch repair system is a DNA repair mechanism that corrects mispaired bases during DNA replication errors. Cancer cells deficient in MMR proteins have a 10(2) to 10(3)-fold increase in the mutation rate. Single nucleotide polymorphisms of mismatch repair genes have been shown to cause a decrease in DNA repair activity. We hypothesized that mismatch repair gene polymorphism could be a risk factor for prostate cancer and p53 Pro/Pro genotype carriers could influence MSH3 and MSH6 polymorphisms.Materials and methodsDNA samples from 110 patients with prostate cancer and 110 healthy controls were analyzed by single strand conformational polymorphism and polymerase chain reaction-restriction fragment length polymorphism to determine the genotypic frequency of 5 polymorphic loci on 2 MMR genes (MSH3 and MSH6) and p53 codon72. The chi-square test was applied to compare genotype frequency between patients and controls.ResultsA significant increase in the G/A+A/A genotype of MSH3 Pro222Pro was observed in patients compared to controls (OR 1.87, 95% CI 1.0-3.5). The frequency of A/G + G/G genotypes of MSH3 exon23 Thr1036Ala also tended to increase in patients (OR 1.57, 95% CI 0.92-2.72). In p53 codon72 Arg/Pro + Pro/Pro carriers the frequency of the AG + GG genotype of MSH3 exon23 was significantly increased in patients compared to controls (OR 2.1, 95% CI 1.05-4.34).ConclusionsTo our knowledge this is the first report of the association of MSH3 gene polymorphisms in prostate cancer. These results suggest that the MSH3 polymorphism may be a risk factor for prostate cancer.
| S-EPMC3940351 | biostudies-literature
Project description:ObjectiveInsulin-like growth factor-binding protein-3 (IGFBP3) is the major protein that binds with insulin-like growth factor-1 (IGF-1) and is considered to be involved in the development and progression of various cancers. We aimed to examine the association between prostate cancer (PCa) and the IGFBP3 gene-202A/C polymorphism.MethodsA comprehensive search within PubMed, EMBASE, and Cochrane Library was conducted to identify all case-control studies up to October 30, 2015, for a meta-analysis. Pooled odds ratios (ORs) and the 95% confidence intervals (CIs) were calculated using the fixed or random effects model.ResultsEighteen studies including 10,538 cases and 10,078 controls were identified. Overall, the CC genotype of IGFBP3-202A/C polymorphism was associated with increased risk of PCa in homozygote comparison (CC vs AA - OR =1.16, 95% CI: 1.08-1.25) and in recessive model (CC vs AA+AC - OR =1.11, 95% CI: 1.04-1.17). In dominant model, the CC/AC genotypes also implicated an increased risk of PCa (CC+AC vs AA - OR =1.11, 95% CI: 1.05-1.19). The C allele of IGFBP3-202A/C polymorphism was the risk allele for PCa relative to the A allele (OR =1.09, 95% CI: 1.05-1.14). Further stratification analysis revealed that the association between -202A/C polymorphism and PCa risk among Caucasians, but not in other ethnicities, was statistically significant (recessive model, OR =1.10, 95% CI: 1.02-1.19). In addition, the IGFBP3-202A/C polymorphism was associated with PCa risk in both population-based and hospital-based studies in homozygote comparison, recessive model, and allele model.ConclusionOur meta-analysis indicates that the IGFBP3-202A/C polymorphism is associated with the risk of PCa, particularly in Caucasians, with the C allele being the risk allele for PCa.
| S-EPMC4940022 | biostudies-literature
Project description:Background:The aim of the present study was to determine whether the interleukin-6 (IL-6) -572G/C polymorphism correlates with prostate cancer. Methods:According to inclusion and exclusion criteria, the association of the IL-6 -572G/C polymorphism with prostate cancer was searched in databases and analyzed using comprehensive meta-analysis software. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the associations. Results:We considered a total of six case-control studies including 2237 patients and 1754 controls and the meta-analysis results showed significant association between the IL-6 -572G/C polymorphism and prostate cancer risk(CC vs GG: OR = 0.49, 95% CI =0.37-0.65;CG vs GG: OR =0.71, 95% CI = 0.58-0.87; the dominant model: OR =0.65, 95% CI = 0.54-0.79;the recessive model: OR =0.70, 95% CI = 0.58-0.85). In stratified analyses by ethnicity, significant associations were found among Asian populations. However, no significant association was found in Caucasian populations. Conclusion:Our findings demonstrated that the -572G/C polymorphism of the IL-6 gene may be a risk factor for the development of prostate cancer in Asians.
| S-EPMC6306959 | biostudies-literature
Project description:Genome-wide association studies (GWASs) identified microseminoprotein-β (MSMB) gene rs10993994 polymorphism was significantly associated with prostate cancer (PC) risk. However, the association between MSMB gene rs10993994 polymorphism and PC risk remains controversial. Therefore, we performed a systematic review and meta-analysis by searching in the databases of PubMed, and Embase. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by using fixed-effect or random-effect models. A total of 11 publications containing 13 case-control studies for rs10993994 polymorphism were included in our analysis. Our data indicated that MSMB gene rs10993994 polymorphism was associated with an increased risk of PC. Stratification analyses of ethnicity suggested rs10993994 polymorphism increased the risk of PC among Caucasians, but not among Asians. In conclusion, this meta-analysis indicates that MSMB gene rs10993994 polymorphism increases the risk of PC.
| S-EPMC5438667 | biostudies-literature
Project description:A prostate cancer risk single nucleotide polymorphism (SNP), rs13426236, is significantly associated with melanophilin (MLPH) expression. To functionally characterize role of the rs13426236 in prostate cancer, we first performed splicing-specific expression Quantitative Trait Loci (eQTL) analysis and refined the significant association of rs13426236 allele G with an increased expression of MLPH splicing variant 4 (V4) (P= 7.61E-5) but not other protein-coding variants (V1-V3) (P>0.05). We then performed an allele-specific reporter assay to determine if SNP-containing sequences functioned as active enhancer. Compared to allele A, allele G of rs13426236 showed significantly higher luciferase activity on the promoter of the splicing transcript V4 (P <0.03) but not on promoter of transcript V1 (P>0.05) in two prostate cancer cell lines (DU145 and 22Rv1). Transfection of MLPH splicing variants showed stronger effect of transcript V4 than V1 on promoting cell proliferation, invasion and anti-apoptotic activities. RNA profiling analysis demonstrated that transcript V4 overexpression caused significant expression changes in glycosylation/glycoprotein and metal-binding gene ontology pathways (FDR<0.01). We also found that both transcripts V4 and V1 were significantly up-regulated in prostate adenocarcinoma (P<2.49E-6) but only transcript V4 up-regulation was associated with poor recurrence free survival (P=0.028, HR=1.63, 95%CI=1.05-2.42) in The Cancer Genome Atlas (TCGA) data. This study provides strong evidence showing that prostate cancer risk SNP rs13426236 up-regulates expression of MLPH transcript V4, which may function as a candidate oncogene in prostate cancer.
2019-08-16 | GSE135888 | GEO
Project description:BACKGROUND: The Glutathione S-transferases (GSTs) comprise a group of enzymes that are critical in the detoxification of carcinogens. In this study the effects of polymorphisms in these genes on the risk of developing oesophageal squamous cell carcinoma (OSCC) were evaluated in a hospital-based case-control study in two South African population groups. Genetic polymorphisms in GSTs were investigated in 245 patients and 288 controls samples by PCR-RFLP analysis. RESULTS: The GSTP1 341T variant was associated with significantly increased risk of developing OSCC as observed from the odds ratios for the GSTP1 341C/T and GSTP1 341T/T genotypes (OR = 4.98; 95%CI 3.05-8.11 and OR = 10.9; 95%CI 2.43-49.1, respectively) when compared to the homozygous GSTP1 341C/C genotype. The risk for OSCC in the combined GSTP1 341C/T and T/T genotypes was higher in tobacco smokers (OR = 7.51, 95% CI 3.82-14.7), alcohol consumers (OR = 15.3, 95% CI 1.81-12.9) and those using wood or charcoal for cooking and heating (OR = 12.1, 95% CI 3.26-49) when compared to those who did not smoke tobacco, or did not consume alcohol or user other forms of fuel for cooking and heating. Despite the close proximity of the two GSTP1 SNPs (313A>G and 341C>T), they were not in linkage disequilibrium in these two population groups (D':1.0, LOD: 0.52, r2: 0.225). The GSTP1 313A/G polymorphism on the other hand, did not display any association with OSSC. The homozygous GSTT1*0 genotype was associated with increased risk of OSCC (OR = 1.71, 95%CI 1.18-2.46) while the homozygous GSTM1*0 genotype was associated with significantly decreased risk of OSCC in the Mixed Ancestry subjects (OR= 0.39, 95%CI 0.25-0.62). CONCLUSIONS: This study shows that the risk of developing OSCC in the South African population can be partly explained by genetic polymorphisms in GST coding genes and their interaction with environmental factors such as tobacco smoke and alcohol consumption.
| S-EPMC2891604 | biostudies-literature