The H6D genetic variation of GDF15 is associated with genesis, progress and prognosis in colorectal cancer

• This work highlighted the role of GDF15 H6D polymorphism in CRC. The presence of G allele in GDF15 H6D leads to susceptibility of CRC pathogenesis. And its G allele is associated with an increased risk of distant metastasis and a poor prognosis in colon cancer.
• For the first time, GDF15 H6D is identified exist somatic mutation in CRC, which is correlated with distant metastasis and had a relatively poor prognosis in male CRC patients.
• GDF15 H6D genetic variant may be considered as a biomarker of tumorgenesis, metastasis and prognosis in colorectal cancer in Chinese population.

BackgroundGrowth 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.MethodsPyrosequencing was used to determine the H6D genotypes. The relationship between the genotypes and clinical characteristics was analyzed.ResultsThe 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 (χ2 = 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, χ2 = 4.820) and had a relatively poor prognosis.ConclusionOur results suggest that the H6D genetic variant may be considered as a biomarker of tumorgenesis, metastasis and prognosis in colorectal cancer in Chinese population.