白介素-22基因多态性与结肠癌相关性的研究

Association of interleukin-22 gene polymorphism with colon cancer

摘要:

目的：白介素-22（interleukin-22，IL-22）是由T细胞和固有淋巴细胞产生的一种白介素-10（interleukin-10，IL-10）家族细胞因子，与炎症形成和肿瘤的发生密切相关。本研究旨在探讨IL-22基因多态性与中国人群结肠癌的关系。方法：采用病例对照研究的方法，收集结肠癌患者540例和健康对照组540例，用5’端核酸外切酶法分析IL-22基因3种常见多态性（－429 C/T、+1046 T/A和+1995A/C）。分类变量间的差异采用Pearson卡方检验，Student’s t检测连续变量间的差异。结果：结肠癌患者中IL-22-429 TT基因型出现频率明显增高（OR=1.69，95%CI=1.24~2.30，P=0.001），－429T等位基因（OR=1.35，95%CI=1.14~1.60，P=0.001）。此结果经过Bonferroni校正依然有统计学意义（P＜0.017）。进一步分层研究后发现分化低的结肠癌患者相对于中高级别分化的结肠癌患者IL-22 -429 TT基因型频率较高（OR=1.45，95%CI=1.02~2.07，P=0.040），而－429 C/T基因多态性与结肠癌的部位、肿瘤大小、生长方式和TNM分期无关。IL-22+1046 T/A及IL-22+1995 A/C基因多态性与结肠癌无关（P=0.980，P=0.750）。结论：IL-22－429C/T基因多态性可能与结肠癌有关。

Abstract:

Objective：To investigate the association of interleukin-22（IL-22） gene polymorphism with colon cancer in the Chinese population，since IL-22 is a member of the interleukin-10 family produced by T cells and innate lymphocytes and is closely associated with the development of inflammation and tumor. Methods：A case-control study was conducted in 540 patients with colon cancer and 540 healthy controls. 5’-Exonuclease assay was used to analyze the three common polymorphisms of the IL-22 gene，i.e.，-429 C/T，+1046 T/A，and +1995 A/C. The Pearson chi-square test was used for comparison of categorical variables，and the Student’s t-test was used for comparison of continuous variables. Results：In the patients with colon cancer，there were significant increases in the frequen－cies of IL-22 -429 TT genotype（odds ratio[OR]=1.69，95% confidence interval[CI]：1.24-2.30，P=0.001） and -429 T allele（OR=1.35，95%CI=1.14 to 1.60，P=0.001）；there were still significant differences after Bonferroni correction（P<0.017）. The further stratifi－cation analysis showed that the patients with poorly differentiated colon cancer had a significantly higher frequency of IL-22 -429 TT genotype than those with moderately differentiated or well-differentiated colon cancer（OR=1.45，95%CI=1.02 to 2.07，P=0.04０），while the polymorphism of IL-22 -429 C/T was not associated with the location，tumor size，growth pattern，and TNM stage of colon cancer. The polymorphisms of IL-22 +1046 T/A and IL-22 +1995 A/C were not associated with colon cancer（P=0.98０ and 0.75０）. Conclusion：The polymorphism of IL-22 -429 C/T may be associated with colon cancer.