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胰岛素样生长因子基因IGFBP3多态性与胃癌易感性关系的研究

Functional polymorphisms in IGFBP3 and gastric cancer risk:a case-control analysis

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【作者】 陈文森王莉娜靳光付王建明华召来谈永飞周炎丁永良沈靖徐耀初沈洪兵

【Author】 Chen Wen-Sen Wang Li-Na Jin Guang-Fu Wang Jian-Min Hua ZaoLai Tan Yong-Fei Zhou Yan Ding Yong-Liang Shen Jing Xu Yao-Chu Shen Hong-Bing Department of Epidemiology and Biostatistics, Nanjing Medical University School of Public Health, Nanjing 210029, China Yangzhong Cancer Institute, Yangzhong City 210623, Jiangsu Province, China Yixing People’ s Hospital, Yixing City 214200, Jiangsu Province, China

【机构】 南京医科大学流行病与卫生统计学系扬中市肿瘤研究所宜兴市人民医院

【摘要】 目的:探讨胰岛素样生长因子结合蛋白3(Insulin— like growth factor binding-protein3,IGFBP-3)基因多态性与胃癌易感性的关系。方法:以人群为基础的病例对照研究,经组织学确诊的胃癌高发区病例576人,并在同地区选择与病例年龄和性别频数匹配的人群对照647人,用PCR- 限制性片段长度多态性(R F L P)进行基因型检测,比较 IGFBP-3 A-202C、IGFBP-3 G2132C不同基因型与胃癌风险的关系,并探讨吸烟、饮酒等环境因素在其中的影响。结果:携带IGFBP-3 2132GC及CC基因型是GG基因型发生胃癌风险性的1.84和2.39倍(校正OR=1.84,95%CI:1.45- 2.33;2.39,95%CI:1.47-3.90)。显性模型研究显示,携带 IGFBP一3 2132GC/CC基因型发生胃癌的风险是GG基因型的1.90倍(校正OR=1.90,95%CI:1.51-2.39);未观察到 IGFBP-3A-202C基因多态性对胃癌危险性的影响。但是两位点(IGFBP-3 A-202C和IGFBP-3 G2132C)之间存在明显的交互作用(Pint<0.0001)。未发现吸烟、饮酒与IGFBP-3 基因多态性在胃癌发生上的交互作用。结论:IGFBP-3 G2132C多态性与胃癌的遗传易感性之间存在关联,并且在两位点(IGFBP-3 A-202C和IGFBP-3 G2132C)之间存在比较明显的位点与位点间的交互作用。

【Abstract】 Objective: To determine whether genetic polymorphisms in insulin-like growth factor binding-protein 3 (IGFBP-3A-202C and IGFBP-3G2132C) were associated with the risks of gastric cancer. Methods: A hospital-based case-control study consisting of 576 incident gastric cancer cases and 647 controls matched on age, sex and race was conducted to investigate the association between polymorphisms in IGFBP-3 and susceptibility to gastric cancer. Genotypes of IGFBP-3 A-202C and G2132C were analyzed by polymerase chain reaction-restriction fragment length polymorphism methods. Results: No significant difference was found for genotype frequencies of A-202C polymorphism between GC cases and controls (P=0.423), while for another polymorphism (G2132C), the variant alleie C remarkably increased the risk of GC (adjusted OR=2.39; 95% CI, 1.47-3.90 for 2132CC, adjusted OR=1.84; 95% CI, 1.45-2.33 for 2132GC, and adjusted OR=1.90, 95 %CI, 1.51-2.39 for 2132GC/CC ), compared with 2132GG wild-type homozygote. Meanwhile, a peculiar locus-locus interaction was found between IGFBP-3 A-202C and IGFBP-3 G2132C (Pint <0.0001), which appeared an antagonistic effects. Conclusion: These data strongly suggested that the G2132C variant in exonl of IGFBP-3 may be an important susceptibility marker for gastric cancer and further functional studies are needed to confirm our findings.

  • 【会议录名称】 第四届中国肿瘤学术大会暨第五届海峡两岸肿瘤学术会议论文集
  • 【会议名称】第四届中国肿瘤学术大会暨第五届海峡两岸肿瘤学术会议
  • 【会议时间】2006-10
  • 【会议地点】中国天津
  • 【分类号】R735.2
  • 【主办单位】中国抗癌协会、中华医学会肿瘤学分会
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