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The association between ATM D1853N polymorphism and breast cancer susceptibility: a meta-analysis.

ABSTRACT: BACKGROUND: Emerging evidence suggests that ataxia telangiectasia-mutated (ATM) is involved in numerous damage repair signaling pathways and cell-cycle checkpoints. Heterozygous carriers of ATM-mutations have an increased risk for the development of breast cancer. The purpose of this study is to evaluate the association between ATM exon39 5557G > A (D1853N, rs1801516) polymorphism and breast cancer susceptibility with the use of a meta-analysis. METHODS: By searching PubMed and Embase databases, a total of 9 epidemiological studies with 4,191 cases and 3,780 controls were identified. Crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) for ATM D1853N polymorphism and breast cancer risk were calculated using fixed- or random-effects model based on the degree of heterogeneity among studies. RESULTS: No significant association between the ATM D1853N polymorphism and breast cancer risk was observed in overall analysis (GA versus GG: OR = 1.18; 95% CI, 0.90-1.53; AA versus GG: OR = 0.77; 95% CI, 0.58-1.03; dominant model: OR = 1.16; 95% CI, 0.89-1.51; and recessive model: OR = 0.78; 95% CI, 0.59-1.04, respectively). CONCLUSION: Our results indicate that ATM D1853N polymorphism is not a risk factor for developing breast cancer.

SUBMITTER: Gao LB

PROVIDER: S-EPMC2936337 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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The association between ATM D1853N polymorphism and breast cancer susceptibility: a meta-analysis.

Gao Lin-Bo LB Pan Xin-Min XM Sun Hong H Wang Xia X Rao Li L Li Li-Juan LJ Liang Wei-Bo WB Lv Mei-Li ML Yang Wen-Zhong WZ Zhang Lin L

Journal of experimental & clinical cancer research : CR 20100827

<h4>Background</h4>Emerging evidence suggests that ataxia telangiectasia-mutated (ATM) is involved in numerous damage repair signaling pathways and cell-cycle checkpoints. Heterozygous carriers of ATM-mutations have an increased risk for the development of breast cancer. The purpose of this study is to evaluate the association between ATM exon39 5557G > A (D1853N, rs1801516) polymorphism and breast cancer susceptibility with the use of a meta-analysis.<h4>Methods</h4>By searching PubMed and Emba ...[more]

PMID: 20799949

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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:Estrogen has played an important role in the development of breast cancer. ER-? PvuII gene polymorphism is in close association with the occurrence risk of breast cancer, but no consensus has been achieved currently.PubMed, Embase, China National Knowledge Infrastructure (CNKI) database, Wanfang database, and VIP database were retrieved to collect the case-control studies on association between ER? 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.A 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 ER? 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 ER? 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, ER? 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).ER? gene Pvu II polymorphism exerts an important function in the progression of breast cancer.

Project description:Research on the polymorphism of breast cancer (BC) helps to search the BC susceptibility gene for mass screening, early diagnosis, and gene therapy, which has become a hotspot in BC research field. Previous studies have suggested associations between rs11200014, rs2981579, and rs1219648 polymorphisms and cancer risk. The aim of this study was to evaluate the relationship between rs11200014, rs2981579, and rs1219648 polymorphism and BC risk.PubMed, Web of science, and the Cochrane Library databases were searched before October 11, 2015, to identify relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of associations. Sensitivity and subgroup analyses were conducted. All included cases should have been diagnosed by a pathological examination.Twenty-six studies published from 2007 to 2015 were included in this meta-analysis. The pooled results showed that there was a significant association between all the 3 variants and BC risk in any genetic model. When stratified by Source of controls, the results showed the same association between rs2981579 polymorphism and BC susceptibility in hospital-based (HB) group, although there was not any genetic model attained statistical correlation in population-based (PB) group. Subgroup analysis was performed on rs1219648 by ethnicity and Source of controls, and the effects remained in Asians, Caucasians, HB, and PB groups.This meta-analysis of case-control studies provides strong evidence that fibroblast growth factor 2 (FGFR2; rs11200014, rs2981579, and rs1219648) polymorphisms are significantly associated with the BC risk. For rs2981579, the association remained in hospital populations, while not in general populations. For rs1219648, the association remained in Asians, Caucasians, hospital populations, and general populations. However, further large-scale multicenter epidemiological studies are warranted to confirm this finding and the molecular mechanism for the associations need to be elucidated in future studies.

Dataset Information

The association between ATM D1853N polymorphism and breast cancer susceptibility: a meta-analysis.

Publications

The association between ATM D1853N polymorphism and breast cancer susceptibility: a meta-analysis.

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