The H6D genetic variation of GDFI 5 is associated with genesis, progress and prognosis in colorectal cancer
The H6D genetic variation of GDFI 5 is associated with genesis, progress and prognosis in colorectal cancer
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GDF15的H6D遗传变异与结直肠癌的发生、进展和预后相关。
DOI：
10.1016/j.prp.2015.08.004
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发表时间：
2015-01-01
影响因子：
2.8
通讯作者：
Lai, Maode
中科院分区：
文献类型：
--
作者：
Wang, Jingyu;Li, Wenfeng;Lai, Maode
背景：生长分化因子15(GDFI5)在多种肿瘤的发生发展中起重要作用。本研究旨在探讨H6D基因多态性与中国人群结直肠癌(CRC)的发生、发展及预后的关系。结果：结直肠癌患者GDFI5H6D基因CG+GG等位基因频率显著高于对照组[优势比(OR)1.543；95%可信区间(95%CI)1.138~2.094，P=0.005]。CG+GG纯合子与CC纯合子相比，结肠癌死亡风险增加[风险比(HR)2.472；95%CI 1.172~5.214；P=0.017]，且CG+GG与远处转移呈正相关(x2=4.087，P=0.043)。与H6D相比，H6D也首次被鉴定为体细胞突变。在肿瘤组织及其配对的正常组织中，突变率为7.2%。携带H6D基因突变的男性结直肠癌患者易发生远处转移(P=0.028，x2=4.820)，且预后较差。结论：H6D基因突变可作为中国人结直肠癌发生、转移和预后的生物标志物。2015爱思唯尔股份有限公司。版权所有。
Background: Growth differentiation factor 15 (GDFI 5) plays important roles in the carcinogenesis of many types of tumors. The aim of this study was to investigate whether H6D polymorphism is contributed to the genesis, progress and prognosis of colorectal cancer (CRC) in Chinese population.Methods: Pyrosequencing was used to determine the H6D genotypes. The relationship between the genotypes and clinical characteristics was analyzed.Results: The frequency of CG + GG genotype in the GDFI 5 H6D polymorphism was significantly increased in CRC patients when compared with controls [odds ratio (OR), 1.543; 95% confidence interval (95% CI), 1.138-2.094, P= 0.005]. We also found that the patients with CG + GG genotype had an increased risk of death from colon cancer than those carrying homozygote CC [hazard ratio (HR), 2.472; 95% CI, 1.172-5.214; P=0.017] and the patients with CG+GG genotype of colon cancer also have a positive correlation with distant metastasis than those carrying homozygote CC (x2 = 4.087, P= 0.043). For the first time, H6D was also identified as somatic mutation when compared the H6D. genotype in tumor tissues and their matched normal tissues, and the mutation rate is 7.2%. The male CRC patients with the H6D mutation were susceptible to distant metastasis (P= 0.028, x2 = 4.820) and had a relatively poor prognosis.Conclusion: Our results suggest that the H6D genetic variant may be considered as a biomarker of tumorgenesis, metastasis and prognosis in colorectal cancer in Chinese population. 2015 Elsevier GmbH. All rights reserved.