title: The H6D genetic variation of GDF15 is associated with genesis, progress and prognosis in colorectal cancer.
abstract: BACKGROUND
  Growth differentiation factor 15 (GDF15) 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 GDF15 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 (χ(2)=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, χ(2)=4.820) and had a relatively poor prognosis.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, School of Medicine, Zhejiang University, Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang, PR China; Department of Pathology, the First Hospital of Jiaxing, Zhejiang, PR China. Electronic address: 11018140@zju.edu.cn.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Chemoradiotherapy, the First Affiliated Hospital of Wenzhou Medical University, Zhejiang, PR China. Electronic address: lwf720325@medmail.com.cn.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Pathology, School of Medicine, Zhejiang University, Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang, PR China. Electronic address: 1026643390@qq.com.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, School of Medicine, Zhejiang University, Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang, PR China. Electronic address: keaidelichen@163.com.
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.affiliation: The Criminal Investigation Detachment of Jiaxing Public Security Bureau, Zhejiang, PR China. Electronic address: 526983038@qq.com.
authors.forename: Meiman
authors.initials: M
authors.lastname: Ding
authors.affiliation: Department of Pathology, School of Medicine, Zhejiang University, Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang, PR China. Electronic address: honghezhang@zju.edu.cn.
authors.forename: Honghe
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pathology, School of Medicine, Zhejiang University, Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang, PR China. Electronic address: lmp@zju.edu.cn.
authors.forename: Maode
authors.initials: M
authors.lastname: Lai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005838:Genotype; D055436:Growth Differentiation Factor 15 / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D016016:Proportional Hazards Models; D055815:Young Adult
chemical_list: C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15
keywords: Colorectal cancer; GDF15; H6D; Mutation; Polymorphism