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Association analysis of rs1695 and rs1138272 variations in GSTP1 gene and breast cancer susceptibility.

ABSTRACT: BACKGROUND:The glutathione S transferases P1 (GSTP1) is one of the common type of the GSTs family. This gene has several genetic polymorphisms that the rs1695 and rs1138272 are the most common variations in this gene. This study aimed to examine the association of these genetic variations with breast cancer risk which was followed by bioinformatics analysis. MATERIAL AND METHODS:In a case-control study, 200 participants including 100 women with breast cancer and 100 healthy women were enrolled. After blood sample collection and DNA extraction, the total genomic DNA was extracted from this sample. The SNPeffects online software was employed to evaluate the effects of rs1695 genetic variation on the GSTP1 protein structure. RESULTS:Our data revealed that there is a significant association between rs1695 genetic variation and the risk of breast cancer in homozygote (OR= 3.1532, 95%CI= 1.1072 to 8.9798, p= 0.0315) and allelic (OR= 1.6098, 95%CI= 1.0577 to 2.4500, p= 0.0263) genetic comparisons. This despite the fact that the rs1138272 polymorphism was not associated with breast cancer risk. Our bioinformatics analysis based on WALTZ output showed that the rs1695 polymorphism reduces the amyloid propensity of the GSTP1 enzyme (dWALTZ= -228.00). CONCLUSIONS:Based on our findings, the rs1695 genetic variation is a genetic risk factor for breast cancer and it could be considered as a biomarker for screening of susceptible women.

SUBMITTER: Farmohammadi A

PROVIDER: S-EPMC7445978 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Association analysis of rs1695 and rs1138272 variations in GSTP1 gene and breast cancer susceptibility.

Farmohammadi Amir A Arab-Yarmohammadi Vahid V Ramzanpour Ramin R

Asian Pacific journal of cancer prevention : APJCP 20200401 4

<h4>Background</h4>The glutathione S transferases P1 (GSTP1) is one of the common type of the GSTs family. This gene has several genetic polymorphisms that the rs1695 and rs1138272 are the most common variations in this gene. This study aimed to examine the association of these genetic variations with breast cancer risk which was followed by bioinformatics analysis.<h4>Material and methods</h4>In a case-control study, 200 participants including 100 women with breast cancer and 100 healthy women ...[more]

PMID: 32334487

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Project description:Background: We obtained conflicting results regarding the relationship between the genetic role of the rs1138272 C/T polymorphism of the GSTP1 (Glutathione S-Transferase pi) gene and the risk of various cancers. Methods: Using the presently available data, a meta-analysis was conducted to comprehensively evaluate the genetic relationship between the GSTP1 rs1138272 polymorphism and cancer susceptibility. Results: A total of 43 studies including 15,688 cases and 17,143 controls were recruited into our quantitative synthesis. In the overall population, we observed an increased risk of overall cancer cases, compared with unrelated controls, in the genetic models of allele T vs. allele C (P-association = 0.007, OR = 1.17), carrier T vs. carrier C (P-association = 0.035, OR = 1.11), TT vs. CC (P-association = 0.002, OR = 1.45), TT vs. CC+CT (P-association = 0.009, OR = 1.42), and CT+TT vs. CC (P-association = 0.027, OR = 1.13). We detected similar positive results within the Asian population. Additionally, there was a significant increase in the incidence of cancer for Africans under all genetic models (all P-association < 0.05, OR > 1). When targeting the Caucasian population, we detected a positive association with the TT vs. CC and TT vs. CC+CT models in the "Colorectal cancer" (P-association < 0.05, OR < 1) and "Head and neck cancer" (P-association < 0.05, OR > 1) subgroups. For the "Lung cancer" subgroup, we observed a slightly increased risk in Caucasians under the models of allele T vs. allele C, carrier T vs. carrier C, CT vs. CC, and CT+TT vs. CC (P-association < 0.05, OR > 1). Conclusion: The TT genotype of the GSTP1 rs1138272 polymorphism is likely related to the susceptibility to overall cancer in the Asian and African populations and, specifically, "Colorectal" and "Head and neck" cancers in the Caucasian population. In addition, the CT genotype of the GSTP1 rs1138272 polymorphism may be linked to the risk of lung cancer in Caucasians. Additional evidence is required to confirm this conclusion.

Project description:BackgroundEstrogen has played an important role in the development of breast cancer. ER-α PvuII gene polymorphism is in close association with the occurrence risk of breast cancer, but no consensus has been achieved currently.MethodsPubMed, Embase, China National Knowledge Infrastructure (CNKI) database, Wanfang database, and VIP database were retrieved to collect the case-control studies on association between ERα gene Pvu II polymorphism and breast cancer risk published before September 1, 2017. Newcastle-Ottawa Scale (NOS) was used to assess the quality of the literatures, Stata 14.0 software was applied for meta-analysis, and the pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated. The subgroup analysis was performed to assess the confounding factors, followed by assessment of publication bias and sensitivity analysis.ResultsA total of 26 studies were enrolled in the analysis based on inclusion criteria, which included 15,360 patients and 26,423 controls. The results demonstrated that ERα gene Pvu II polymorphism was in significant association with the decrease of breast cancer risk in 3 genetic models (C vs T, OR = 0.962, 95% CI = 0.933-0.992, P = .012; CC vs TT, OR = 0.911, 95% CI = 0.856-0.969, P = .003; CC vs TT/CT, OR = 0.923, 95% CI = 0.874-0.975, P = .004). Subgroup analysis was conducted on the basis of ethnicity and source of controls, whose results illustrated that ERα gene Pvu II polymorphism was in significant association with the decrease of breast cancer risk in Asians rather than in Caucasians (CC vs TT, OR = 0.862, 95% CI = 0.750-0.922, P = .038; CC vs TT/CT, OR = 0.851, 95% CI = 0.755-0.959, P = .008). In population-based subgroup rather than in hospital-based subgroup, ERα gene Pvu II polymorphism was in significant association with the decrease of breast cancer risk in the allele model, homozygous model, dominant model, and recessive model (C vs T, OR = 0.943, 95% CI = 0.911-0.977, P = .001; CC vs TT, OR = 0.878, 95% CI = 0.817-0.944, P = .000; CC/CT vs TT, OR = 0.936, 95% CI = 0.881-0.994, P = .031; CC vs TT/CT, OR = 0.902, 95% CI = 0.847-0.960, P = .001).ConclusionERα gene Pvu II polymorphism exerts an important function in the progression of breast cancer.

Dataset Information

Association analysis of rs1695 and rs1138272 variations in GSTP1 gene and breast cancer susceptibility.

Publications

Association analysis of rs1695 and rs1138272 variations in GSTP1 gene and breast cancer susceptibility.

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