Association between ATM rs1801516 polymorphism and cancer susceptibility: a meta-analysis involving 12,879 cases and 18,054 controls.
Association between ATM rs1801516 polymorphism and cancer susceptibility: a meta-analysis involving 12,879 cases and 18,054 controls.
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ATM rs1801516 多态性与癌症易感性之间的关联：一项涉及 12,879 例病例和 18,054 名对照的荟萃分析
DOI：
10.1186/s12885-018-4941-1
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发表时间：
2018-11-01
期刊：
影响因子：
3.8
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Gu Y;Shi J;Qiu S;Qiao Y;Zhang X;Cheng Y;Liu Y
背景：Ataxia毛细血管扩张突变基因（Ataxia telangi扩张突变，ATM）在DNA损伤应答中起关键作用，与恶性肿瘤的侵袭和转移有关。流行病学研究表明，ATM rs1801516多态性与不同类型的癌症存在关联，但结果并不一致。为了进一步评估ATM rs1801516多态性对癌症风险的影响，我们进行了meta分析。方法：通过检索PubMed、Web of Science和Embase数据库，根据特定的纳入标准对研究进行筛选。计算隐性、显性、共显性和过显性遗传模型下的合并优势比（ORs）和相应的95%置信区间（CIs），以估计rs1801516多态性与癌症风险之间的关系。结果：本研究共纳入37项研究，12879例病例和18054例对照。在总体比较中，rs1801516多态性与癌症风险之间未发现显著相关性（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）。由region-specified人口,然而,在子群分析重大协会在欧洲被发现(AA vs GG + GA: = 0.79, 95% CI, 0.65 - -0.96, P = 0.017; AA vs GG: = 0.79, 95% CI, 0.65 - -0.96, P = 0.017),南美(AA + GA vs GG: = 2.15, 95% CI, 1.37 - -3.38, P = 0.001; GA vs GG: = 2.19, 95% CI, 1.38 - -3.47, P = 0.001; GG + AA vs GA: = 0.46, 95% CI, 0.29 - -0.72, P = 0.001),和亚洲(AA vs GG + GA: = 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)。亚组分析还显示，与携带GG基因型的受试者相比，携带纯合子AA的受试者患乳腺癌的风险降低（AA与GG: OR = 0.76, 95% CI, 0.59-0.98, P = 0.035），并且在有家族史的受试者中，纯合子AA与癌症风险降低相关（AA与GG: OR = 0.68, 95% CI, 0.47-0.98, P = 0.039）。结论：ATM rs1801516多态性与人群总体癌症风险无关。然而，在亚组分析中，这种多态性与乳腺癌风险尤其相关；此外，它与欧洲人、南美人、亚洲人以及有家族史的人的总体癌症风险有关。
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.
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