Hashemi Mohammad, Moazeni-Roodi Abdolkarim, Ghavami Saeid
Cellular and Molecular Research Center, Deputy for Research, Zahedan University of Medical Sciences, Zahedan, Iran.
Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
J Cell Biochem. 2019 May;120(5):7199-7210. doi: 10.1002/jcb.27994. Epub 2018 Oct 28.
Several studies inspected the relationship between caspase-3 (CASP3) polymorphisms and the risk of several human cancers, but the findings remain controversial. We conducted a meta-analysis aiming to inspect the association between CASP3 rs1049216 T>C, rs12108497 C>T, rs4647603 G>A, rs4647602 C>A, rs6948 T>G, rs2705897 A>C, and rs113420705 G>A polymorphisms and cancer risk. Eligible studies were recognized by searching the Web of Science, PubMed, Scopus, and Google Scholar databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to quantitatively evaluate the association between each polymorphism of CASP3 and cancer risk. The rs4647603 variant significantly increased the risk of cancer in an overdominant (OR, 1.44; 95% CI, 1.03-2.01; P = 0.03; AG vs AA+GG) inheritance model. Regarding the rs4647602 variant, the findings revealed that this variant was associated with protection against cancer in homozygous codominant (OR, 0.67; 95% CI, 0.56-0.80; P < 0.00001; AA vs CC), dominant (OR, 0.84; 95% CI, 0.73-0.96; P = 0.009; AC+AA vs CC), recessive (OR, 0.70; 95% CI, 0.61-0.79; P < 0.00001; AA vs AC+CC), and allele (OR, 0.81; 95% CI, 0.75-0.88; P = 0.00001; A vs C) models. The findings suggested that the rs2705897 variant significantly decreased the risk of cancer in heterozygous codominant (OR, 0.80; 95% CI, 0.67-0.94; P = 0.009; AC vs AA), dominant (OR, 0.81; 95% CI, 0.69-0.95; P = 0.009; AC+CC vs AA), overdominant (OR, 0.80; 95% CI, 0.68-0.95; P = 0.01; AC vs CC+AA), and allele (OR, 0.85; 95% CI, 0.74-0.97; P = 0.02; C vs A) models. The results did not support an association between CASP3 rs1049216 and rs6948 polymorphisms and cancer risk. In summary, the findings of this meta-analysis support an association between CASP3 polymorphisms and cancer risk. Larger and well-designed studies are desired to evaluate these associations in detail.
多项研究考察了半胱天冬酶 - 3（CASP3）基因多态性与多种人类癌症风险之间的关系，但研究结果仍存在争议。我们进行了一项荟萃分析，旨在考察CASP3基因的rs1049216 T>C、rs12108497 C>T、rs4647603 G>A、rs4647602 C>A、rs6948 T>G、rs2705897 A>C和rs113420705 G>A多态性与癌症风险之间的关联。通过检索Web of Science、PubMed、Scopus和谷歌学术数据库来识别符合条件的研究。估计合并优势比（OR）及95%置信区间（CI），以定量评估CASP3各多态性与癌症风险之间的关联。在超显性遗传模型（OR，1.44；95% CI，1.03 - 2.01；P = 0.03；AG 对比 AA + GG）中，rs4647603变异显著增加了癌症风险。关于rs4647602变异，研究结果显示，在纯合共显性模型（OR，0.67；95% CI，0.56 - 0.80；P < 0.00001；AA对比CC）、显性模型（OR，0.84；95% CI，0.73 - 0.96；P = 0.009；AC + AA对比CC）、隐性模型（OR，0.70；95% CI，0.61 - 0.79；P < 0.00001；AA对比AC + CC）和等位基因模型（OR，0.81；95% CI，0.75 - 0.88；P = 0.00001；A对比C）中，该变异与预防癌症有关。研究结果表明，在杂合共显性模型（OR，0.80；95% CI，0.67 - 0.94；P = 0.009；AC对比AA）、显性模型（OR，0.81；95% CI，0.69 - 0.95；P = 0.009；AC + CC对比AA）、超显性模型（OR，0.80；95% CI，0.68 - 0.95；P = 0.01；AC对比CC + AA）和等位基因模型（OR，0.85；95% CI，0.74 - 0.97；P = 0.02；C对比A）中，rs2705897变异显著降低了癌症风险。结果不支持CASP3基因的rs1049216和rs6948多态性与癌症风险之间存在关联。总之，这项荟萃分析的结果支持CASP3基因多态性与癌症风险之间存在关联。需要开展更大规模且设计良好的研究来详细评估这些关联。
