Malik Manzoor Ahmad, Gupta Annapurna, Zargar Showkat Ali, Mittal Balraj
Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226014, India.
Tumour Biol. 2013 Oct;34(5):3049-57. doi: 10.1007/s13277-013-0870-4. Epub 2013 Jun 14.
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.
结直肠癌缺失基因（DCC）中的基因改变先前已被报道与多种人类癌症的转移相关。我们研究了克什米尔山谷地区DCC中潜在功能性单核苷酸多态性（SNP）与食管癌（EC）和胃癌（GC）易感性之间的关联。我们采用聚合酶链反应-限制性片段长度多态性方法，对克什米尔山谷地区135例EC患者、108例GC患者以及195例年龄和性别匹配的对照者的DCC基因的两个SNP（DCC rs714（A>G）和DCC rs2229080（C>G））进行基因分型。使用SPSS通过二元逻辑回归估计患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）多态性与癌症风险之间的关联。观察到EC和GC病例与相应对照组之间DCC rs714（A>G）基因型分布存在显著差异（优势比（OR）=1.92；P=0.03；P趋势=0.04；错误发现率（FDR）P校正=0.03：OR=2.15；P=0.02；P趋势=0.01；FDR P校正=0.03）。但在DCC rs2229080（C>G）中未观察到此类关联。此外，DCC rs714（A>G）AA基因型显示胃鳞状细胞癌（OR=5.63；P=0.02；FDR P校正=0.01）和胃腺癌（OR=2.15；P=0.02；FDR P校正=0.01）的风险均显著增加。吸烟和咸茶均与EC和GC独立相关，但基因-环境相互作用并未进一步调节风险。荟萃分析还表明DCC rs714（A>G）多态性与癌症存在独立和总体关联（P=0.000）。总之，DCC rs714（A>G）中的基因变异调节了高风险克什米尔人群患EC和GC的风险。
