Role of genetic variants of deleted in colorectal carcinoma (DCC) polymorphisms and esophageal and gastric cancers risk in Kashmir Valley and meta-analysis
Role of genetic variants of deleted in colorectal carcinoma (DCC) polymorphisms and esophageal and gastric cancers risk in Kashmir Valley and meta-analysis
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DOI：
10.1007/s13277-013-0870-4
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发表时间：
2013-10-01
期刊：
影响因子：
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通讯作者：
Mittal, Balraj
中科院分区：
文献类型：
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作者：
Malik, Manzoor Ahmad;Gupta, Annapurna;Mittal, Balraj
结直肠癌(DCC)基因缺失的遗传改变与多种人类肿瘤的转移有关。我们研究了DCC中潜在功能SNPs与克什米尔山谷食道癌和胃癌易感性之间的关系。采用聚合酶链式反应-限制性片段长度多态性方法，对克什米尔河谷135例EC患者、108例GC患者和195例正常对照DCC基因DCC rs714(A>；G)和DCC rs2229080(C>；G)两个SNP进行了基因分型。用SPSS软件进行二元Logistic回归分析，估计发生EC和GC的风险。我们还对DCC rs714(A>；G)进行了荟萃分析，并评估了DCC rs714(A>；G)基因多态与癌症风险之间的关系。DCC rs714(A>；G)基因型在EC和GC组与相应对照组之间的分布差异有统计学意义(优势比OR=1.92；P=0.03；P趋势=0.04；假发现率Pcorr=0.03：OR=2.15；P=0.02；P趋势=0.01；FDR Pcorr=0.03)。但在DCC rs2229080(C>；G)中没有观察到这种关联。此外，DCC rs714(A>；G)AA基因型显著增加了患胃鳞癌(OR=5.63；P=0.02；FDR Pcorr=0.01)和胃腺癌(OR=2.15；P=0.02；FDR Pcorr=0.01)的风险。吸烟和咸茶与EC和GC独立相关，但基因-环境交互作用并未进一步调节风险。Meta分析还显示DCCrs714(A>；G)基因多态与癌症之间存在独立和整体的关联(P=0.000)。总之，DCC rs714(A>；G)的遗传变异调节了克什米尔高危人群中EC和GC的风险。
Genetic alterations in the deleted in colorectal carcinoma (DCC) gene have been a priori reported to associate with metastasis in variety of human cancers. We investigated the association between potentially functional SNPs in DCC and susceptibility to esophageal (EC) and gastric (GC) cancers in Kashmir Valley. We genotyped two SNPs DCC rs714 (A > G) and DCC rs2229080 (C > G) of DCC in 135 EC patients, 108 GC patients, and 195 controls matched by age and sex in Kashmir Valley by polymerase chain reaction-RFLP method. Risk for developing EC and GC was estimated by binary logistic regression by using SPSS. We also performed a meta-analysis on DCC rs714 (A > G) and evaluated the association between the DCC rs714 (A > G) polymorphisms and cancer risk. A significant difference in DCC rs714 (A > G) genotype distribution between EC and GC cases and corresponding control groups was observed (odds ratio (OR) = 1.92; P = 0.03; P-trend = 0.04; false discovery rate (FDR) Pcorr = 0.03: OR = 2.15; P = 0.02; P-trend = 0.01; FDR Pcorr = 0.03). But no such association was observed in DCC rs2229080 (C > G). Further, DCC rs714 (A > G) AA genotype showed significantly increased risk for both gastric squamous cell carcinoma (OR = 5.63; P = 0.02; FDR Pcorr = 0.01) and gastric adenocarcinoma (OR = 2.15; P = 0.02; FDR Pcorr = 0.01). Smoking and salted tea are independently associated with both EC and GC, but gene-environment interaction did not further modulate the risk. Meta-analysis also suggested both independent and overall association of DCC rs714 (A > G) polymorphism with cancer (P = 0.000). In conclusion, genetic variations in DCC rs714 (A > G) modulate risk of EC and GC in high-risk Kashmir population.