Dataset Information

FAS-1377 G/A (rs2234767) polymorphism and cancer susceptibility: a meta-analysis of 17,858 cases and 24,311 controls.

ABSTRACT: BACKGROUND AND OBJECTIVES:Disruption of apoptosis has been implicated in carcinogenesis. Specifically, various single-nucleotide polymorphisms (SNPs) in apoptotic genes, such as FAS-1377 G/A SNP, have been associated with cancer risk. FAS-1377 G/A SNP has been shown to alter FAS gene promoter transcriptional activity. Down-regulation of FAS and cell death resistance is key to many cancers, but an association between FAS-1377 G/A SNP and cancer risk is uncertain. Therefore, we conducted a meta-analysis of the current literature to clarify this relationship. METHODOLOGY/PRINCIPAL FINDINGS:From PubMed and Chinese language (CNKI and WanFang) databases, we located articles published up to March 5, 2013, obtaining 44 case-control studies from 41 different articles containing 17,858 cases and 24,311 controls based on search criteria for cancer susceptibility related to the FAS gene -1377 G/A SNP. Odds ratios (ORs) and 95% confidence intervals (CI) revealed association strengths. Data show that the -1377 G allele was protective against cancer risk. Similar associations were detected in "source of control," ethnicity and cancer type subgroups. Lower cancer risk was found in both smokers with a GG+GA genotype and in non-smokers with the GG+GA genotype, when compared to smokers and nonsmokers with the AA genotype. Males carrying the -1377G allele (GG+GA) had lower cancer incidence than those with the AA genotype. Individuals who carried both FAS-1377(GG+GA)/FASL-844(TT+TC) genotypes appeared to have lower risk of cancer than those who carried both FAS-1377 AA/FASL-844 CC genotypes. CONCLUSIONS/SIGNIFICANCE:The FAS-1377 G/A SNP may decrease cancer risk. Studies with larger samples to study gene-environment interactions are warranted to understand the role of FAS gene polymorphisms, especially -1377 G/A SNP, in cancer risk.

SUBMITTER: Zhong-Xing Z

PROVIDER: S-EPMC3754923 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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FAS-1377 G/A (rs2234767) polymorphism and cancer susceptibility: a meta-analysis of 17,858 cases and 24,311 controls.

Zhong-Xing Zhou Z Yuan-Yuan Mi M Hai Zhen Ma M Jian-Gang Zou Z Li-Feng Zhang Z

PloS one 20130827 8

<h4>Background and objectives</h4>Disruption of apoptosis has been implicated in carcinogenesis. Specifically, various single-nucleotide polymorphisms (SNPs) in apoptotic genes, such as FAS-1377 G/A SNP, have been associated with cancer risk. FAS-1377 G/A SNP has been shown to alter FAS gene promoter transcriptional activity. Down-regulation of FAS and cell death resistance is key to many cancers, but an association between FAS-1377 G/A SNP and cancer risk is uncertain. Therefore, we conducted a ...[more]

PMID: 24014103

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Project description:BACKGROUND:Ataxia telangiectasia mutated (ATM) gene plays a key role in response to DNA lesions and is related to the invasion and metastasis of malignancy. Epidemiological studies have indicated associations between ATM rs1801516 polymorphism and different types of cancer, but their results are inconsistent. To further evaluate the effect of ATM rs1801516 polymorphism on cancer risk, we conducted this meta-analysis. METHODS:Studies were identified according to specific inclusion criteria by searching PubMed, Web of Science, and Embase databases. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) under recessive, dominant, codominant, and overdominant models of inheritance were calculated to estimate the association between rs1801516 polymorphism and cancer risk. RESULTS:A total of 37 studies with 12,879 cases and 18,054 controls were included in our study. No significant association was found between rs1801516 polymorphism and cancer risk in overall comparisons (AA vs GG?+?GA: OR?=?0.91, 95% CI, 0.78-1.07; AA+GA vs GG: OR?=?1.00, 95% CI, 0.90-1.11; AA vs GG: OR?=?0.89, 95% CI, 0.75-1.06; GA vs GG: OR?=?1.01, 95% CI, 0.91-1.13; GG?+?AA vs GA: OR?=?1.00, 95% CI, 0.88-1.10). However, after subgroup analyses by region-specified population, significant associations were found in European (AA vs GG?+?GA: OR?=?0.79, 95% CI, 0.65-0.96, P?=?0.017; AA vs GG: OR?=?0.79, 95% CI, 0.65-0.96, P?=?0.017), South American (AA+GA vs GG: OR?=?2.15, 95% CI, 1.37-3.38, P?=?0.001; GA vs GG: OR?=?2.19, 95% CI, 1.38-3.47, P?=?0.001; GG?+?AA vs GA: OR?=?0.46, 95% CI, 0.29-0.72, P?=?0.001), and Asian (AA vs GG?+?GA: OR?=?7.45, 95% CI, 1.31-42.46, P?=?0.024; AA vs GG: OR?=?7.40, 95% CI, 1.30-42.19, P?=?0.024). Subgroup analyses also revealed that compared with subjects carrying a GG genotype, those carrying a homozygote AA had a decreased risk for breast cancer (AA vs GG: OR?=?0.76, 95% CI, 0.59-0.98, P?=?0.035), and the homozygote AA was associated with decreased cancer risk in subjects with family history (AA vs GG: OR?=?0.68, 95% CI, 0.47-0.98, P?=?0.039). CONCLUSIONS:ATM rs1801516 polymorphism is not associated with overall cancer risk in total population. However, for subgroup analyses, this polymorphism is especially associated with breast cancer risk; in addition, it is associated with overall cancer risk in Europeans, South Americans, Asians, and those with family history.

Project description:BACKGROUND:There have been several case-control studies to assess the relationship between the transforming growth factor-?1 (TGF-?1) T?+?869C (rs1982073)/C-509T (rs1800469) gene polymorphism and lung cancer in recent years; however, the results remain controversial. In this study, we investigated the potential correlation between the TGF-?1 T?+?869C/C-509T polymorphism and increased risk of lung cancer through meta-analysis. METHODS:We searched the Cochrane Library database, Embase, PubMed, Web of Science, China National Knowledge Infrastructure, and the Wanfang Data Information Service platform to identify relevant case-control studies in strict accordance with the inclusion and exclusion criteria. The odds ratio (OR) and its 95% confidence interval (95% CI) were used to evaluate the correlation between TGF-?1 gene polymorphism and lung tumor risk. Sensitivity analysis and Egger test were used to evaluate the stability of the results and possible publication bias. RESULTS:A total of 8 studies, with 3680 patients and 4018 controls, were included. The meta-analysis revealed that there was no conspicuous correlation between the TGF-?1 T?+?869C (rs1982073)/C-509T (rs1800469) variant and lung cancer in the overall population. For TGF-?1 C-509T, a significant decreased risk was identified in patients with nonsmall-cell lung cancer (NSCLC) in the analysis stratified by disease (TT vs CT?+?CC: P?=?.02, OR?=?0.49, 95% CI 0.27-0.90). However, for TGF-?1 T?+?869C, subgroup analysis showed no correlation between the T?+?869C polymorphism and lung cancer susceptibility in patients with NSCLC. In the subgroup analysis by ethnicity, no distinct association was observed between T?+?869C (rs1982073)/C-509T (rs1800469) polymorphism and lung cancer susceptibility in the Asian and Caucasian groups. Moreover, no significant association was found in the analysis of groups stratified by age, sex, and smoking history. CONCLUSION:The TGF-?1 T?+?869C (rs1982073) and C-509T (rs1800469) polymorphisms are not implicated in lung cancer susceptibility in the overall population. However, our analysis indicated that the C-509T (rs1800469) polymorphism decreases the risk of lung cancer in patients with NSCLC.

Dataset Information

FAS-1377 G/A (rs2234767) polymorphism and cancer susceptibility: a meta-analysis of 17,858 cases and 24,311 controls.

Publications

FAS-1377 G/A (rs2234767) polymorphism and cancer susceptibility: a meta-analysis of 17,858 cases and 24,311 controls.

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