Gu Haijuan, Yang Li, Sun Qingmin, Zhou Bo, Tang Naping, Cong Rihong, Zeng Ying, Wang Bin
Key Laboratory of Reproductive Medicine, Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Clin Cancer Res. 2008 Jun 1;14(11):3627-32. doi: 10.1158/1078-0432.CCR-07-4808.
It has been shown that the expression of the receptor for advanced glycation end products (RAGE) is closely associated with invasion and metastasis in gastric cancer. A Gly82Ser polymorphism in exon 3 of RAGE gene was identified and thought to have an effect on the functions of its protein. Therefore, the goal of the present study was to investigate whether the polymorphism is involved in the development or progression of gastric cancer.
In the hospital-based case-control study, the RAGE genotypes were determined using PCR-RFLP in 566 individuals (283 gastric cancer patients and 283 age- and sex-matched controls).
The distribution of genotype was significantly different between cases and controls (P = 0.038). Compared with the wild-type 82Gly/Gly carriers, subjects with the variant genotypes (82Gly/Ser and 82Ser/Ser) had a significantly higher risk of gastric cancer (adjusted odds ratio, 1.47; 95% confidence interval, 1.05-2.06). Moreover, the elevated gastric cancer risk was especially evident in younger individuals (ages < or =58 years), nonsmokers, and rural subjects. Further analyses revealed that the variant genotypes were associated with adjacent organ invasion in the subanalysis of gastric cancer patients.
Our findings indicate that the RAGE Gly82Ser polymorphism may confer not only an increased risk of gastric cancer but also with invasion of gastric cancer in the Chinese population.
已表明晚期糖基化终末产物受体（RAGE）的表达与胃癌的侵袭和转移密切相关。RAGE基因外显子3中的Gly82Ser多态性已被鉴定出来，并被认为对其蛋白质功能有影响。因此，本研究的目的是调查该多态性是否参与胃癌的发生或发展。
在这项基于医院的病例对照研究中，采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对566名个体（283例胃癌患者和283例年龄及性别匹配的对照）进行RAGE基因分型测定。
病例组和对照组之间基因型分布存在显著差异（P = 0.038）。与野生型82Gly/Gly携带者相比，携带变异基因型（82Gly/Ser和82Ser/Ser）的受试者患胃癌的风险显著更高（调整后的优势比为1.47；95%置信区间为1.05 - 2.06）。此外，胃癌风险升高在较年轻个体（年龄≤58岁）、非吸烟者和农村受试者中尤为明显。进一步分析显示，在胃癌患者的亚组分析中，变异基因型与邻近器官侵犯有关。
我们的研究结果表明，RAGE基因的Gly82Ser多态性可能不仅增加中国人群患胃癌的风险，还与胃癌的侵袭有关。
