Abstract：【Objective】To investigate the relationship between single nucleotide polymorphism at rs4464148 of Smad7 Gene and the risk and prognosis of cholangiocarcinoma. 【Methods】The bile duct tissues of 70 patients with cholangiocarcinoma (observation group) and 40 patients with non neoplastic diseases (control group) who underwent surgical resection from January 2010 to January 2014 in Hunan Provincial People's Hospital were taken. All patients with cholangiocarcinoma did not receive adjuvant radiotherapy and chemotherapy before operation. The single nucleotide polymorphism of rs4464148 locus of Smad7 Gene in the observation group and the control group was detected by LDR-PCR, and the relationship between different genotypes and the risk and prognosis of cholangiocarcinoma was analyzed.【Results】There were AA, AG and GG genotypes at rs4464148 locus of Smad7 gene. The frequencies of AG/ GG genotype and G allele in the observation group were higher than those in the control group (P<0.05). Logistic multivariate regression analysis showed that the OR values of AG and AG/GG genotypes were 1.4 and 1.35 respectively. AG/GG genotype may be the pathogenic factor of cholangiocarcinoma. There was significant difference in the frequencies of AG/GG and AA genotypes in patients with lymph node metastasis, no recurrence or progression (P<0.05). The 3-year survival rate of patients with rs4464148 AG/GG genotype was lower than that of patients with AA genotype, but the difference was not statistically significant (P>0.05).【Conclusion】The AG/GG genotype at rs4464148 locus of Smad7 gene may be a risk factor for cholangiocarcinoma and may be an index to judge the prognosis of cholangiocarcinoma.
[1] Banales J M, Marin J , Lamarca A,et al.Cholangiocarcinoma 2020: the next horizon in mechanisms and management[J].Nat Rev Gastroenterol Hepatol,2020, 17(9):557-588.
[2] BRODERICK P, CARVAJALCARMONA L, PITTMAN A M, et al. A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk[J].Nat Genet,2007, 39(11):1315-1317.
[3] LOH Y H, MITROU P N, WOOD A, et al. SMAD7 and MGMT genotype variants and cancer incidence in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk Study[J].Cancer Epidemiol,2011, 35(4):369-374.
[4] DAMAVAND B, DERAKHSHANI S, SAEEDI N, et al. Intronic polymorphisms of the SMAD7 gene in association with colorectal cancer[J].Asian Pac J Cancer Prev,2015, 16(1):41-44.
[5] MENG L, TIAN Z, WANG Y, et al. Predictive and prognostic molecular markers for cholangiocarcinoma in Han Chinese population[J].Int J Clin Experimental Med,2015, 8(8):13680-13689.
[6] KIM S, HAN J, LEE S K, et al. Smad7 acts as a negative regulator of the epidermal growth factor (EGF) signaling pathway in breast cancer cells[J].Cancer Letters,2012, 314(2):147-154.
[7] HUANG Q, LIU L, LIU C H, et al. Expression of Smad7 in cholangiocarcinoma: prognostic significance and implications for tumor metastasis[J].Asian Pac J Cancer Prev,2012, 13(10):5161-5165.
[8] LUO L, LI N, LV N, et al. SMAD7: a timer of tumor progression targeting TGF-β signaling[J].Tumor Biol,2014, 35(9):8379-8385.
[9] THEOHARI I, GIANNOPOULOU I, MAGKOU C, et al. Differential effect of the expression of TGF-β pathway inhibitors, Smad-7 and Ski, on invasive breast carcinomas: relation to biologic behavior[J].Apmis,2012, 120(2):92-100.
[10] EKMAN M, MU Y, LEE S Y, et al. APC and Smad7 link TGF-β type Ⅰ receptors to the microtubule system to promote cell migration[J].Molecular Biol Cell,2012, 23(11):2109-2121.
2021, Vol. 38 
