Dataset Information

Genetic polymorphism of p53, but not GSTP1, is association with susceptibility to esophageal cancer risk - a meta-analysis.

ABSTRACT: A number of studies have evaluated two functional polymorphisms on p53 Arg72Pro and GSTP1 Ile105Val, in relation to esophageal cancer susceptibility. However, the results remain conflicting rather than conclusive. This meta-analysis on 2919 cases and 4074 controls for p53 Arg72Pro and 1885 cases and 2194 controls for GSTP1 Ile105Val from 13 published case-control studies showed that no significant general main effects for GSTP1 Ile105Val on esophageal cancer risk. However, we found that the p53 Arg72Pro was associated with an increased risk of esophageal cancer ((Pro/Arg +Pro/Pro) versus Arg/Arg: OR=1.20, 95%CI=1.06-1.36) without any between-study heterogeneity. In the stratified analysis by ethnicity, we found that the increased esophageal cancer risk associated with p53 Arg72Pro polymorphism was more evident in Asian group ((Pro/Arg +Pro/Pro) versus Arg/Arg: OR=1.35, 95%CI=1.14-1.60, P=0.09 for heterogeneity test), although we still failed to find any significant association between GSTP1 Ile105Val polymorphism and esophageal cancer risk in different ethnicity. These results suggest that p53 Arg72Pro polymorphism, but not GSTP1 Ile105Val, may contribute to esophageal cancer development, especially in Asian. Additional well-designed large studies were required for the validation of this association.

SUBMITTER: Zhao Y

PROVIDER: S-EPMC2934729 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Genetic polymorphism of p53, but not GSTP1, is association with susceptibility to esophageal cancer risk - a meta-analysis.

Zhao Yaping Y Wang Furu F Shan Shunlin S Zhao Yiqi Y Qiu Xueming X Li Xiangyang X Jiao Feng F Wang Jianguo J Du Yunxiang Y

International journal of medical sciences 20100901 5

A number of studies have evaluated two functional polymorphisms on p53 Arg72Pro and GSTP1 Ile105Val, in relation to esophageal cancer susceptibility. However, the results remain conflicting rather than conclusive. This meta-analysis on 2919 cases and 4074 controls for p53 Arg72Pro and 1885 cases and 2194 controls for GSTP1 Ile105Val from 13 published case-control studies showed that no significant general main effects for GSTP1 Ile105Val on esophageal cancer risk. However, we found that the p53 ...[more]

PMID: 20827430

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Project description:Background and Objectives: One of the most frequent genetic alterations reported to date in prostate cancer (PC) is aberrant methylation of glutathione transferase P1 (GSTP1). Taking into consideration the involvement of oxidative stress in PC pathogenesis and recent advances in scientific understanding of the role of GSTP1*Ala114Val rs1138272 polymorphism in carcinogenesis, we hypothesized that this single-nucleotide polymorphism (SNP) influences the risk of PC independently of, or in combination with, other GST polymorphisms, including GSTP1*IIe105Val rs1695 or GSTM1 and GSTT1 deletion polymorphisms. Materials and Methods: Genotyping was performed in 237 PC cases and in 236 age-matched controls by multiplex polymerase chain reaction (PCR) for deletion of GST polymorphisms and by quantitative PCR for SNPs. Results: We found that carriers of either GSTP1*Val (rs1138272) or GSTP1*Val (rs1695) variant alleles had a PC risk compared to individuals with both referent alleles (OR = 4.93, 95%CI: 2.89-8.40, p < 0.001 and OR = 1.8, 95%CI: 1.19-2.73, p = 0.006, respectively). Additionally, in a haplotype analysis we found that individuals with GSTP1*C haplotype, represented by both variant alleles (GSTP1*Val rs1695 + GSTP1*Val rs1138272), had a 5.46 times higher risk of PC development compared to individuals with the most frequent haplotype (95%CI = 2.56-11.65, p < 0.001), suggesting a potential role of those variants in PC susceptibility. A regression analysis on the number of risk-associated alleles per individual (GSTM1*active, GSTT1*null, GSTP1*Val rs1695 and GSTP1*Val rs1138272) showed a significant increase in the risk of developing PC, from 3.65-fold in carriers of two risk alleles (95%CI = 1.55-8.61, p = 0.003) to an approximately 12-fold increase in carriers of all four risk alleles (95%CI = 3.05-44.93, p < 0.001). Conclusion: Prostate cancer may be influenced by multiple glutathione transferase (GST) polymorphic genes, especially GSTP1, highlighting the role of gene-gene interactions in human susceptibility to this cancer.

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.

Dataset Information

Genetic polymorphism of p53, but not GSTP1, is association with susceptibility to esophageal cancer risk - a meta-analysis.

Publications

Genetic polymorphism of p53, but not GSTP1, is association with susceptibility to esophageal cancer risk - a meta-analysis.

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