−509CgtT polymorphism in the TGFβ1 gene promote

Authors: Peng Qi Yueming Chen Hao Wang Meng Fang Qiang Ji Yunpeng Zhao Xiaojuan Sun Yan Liu Chunfang Gao

Publish Date: 2009/01/25

Volume: 58, Issue: 9, Pages: 1433-1440

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Abstract

Hepatocellular carcinoma HCC is one of the most common malignant tumors worldwide The risk for developing HCC increases with severity of inflammation and fibrosis Transforming growth factorβ1 TGFβ1 is most frequently upregulated in tumor cells The most studied −509CT polymorphism of TGFβ1 gene has been associated with colorectal gynecologic and lung cancers To assess whether this polymorphism in TGFβ1 gene is associated with susceptibility to and/or clinicopathologic characteristics of HBVrelated HCC a total of 575 patients with chronic HBV infection and 299 healthy volunteers with no evidence of recent or remote HBV infection were prospectively enrolled The patients were divided into two groups those without n = 196 and those with HCC n = 379 These 379 HCC patients with chronic HBV infection were designated as cases the remaining 196 patients without HCC and 299 healthy volunteers served as disease and healthy controls respectively −509CT polymorphism in the TGFβ1 gene promoter was studied using restriction fragmentlength polymorphism In addition tumor tissues of liver n = 60 were obtained from the studied HCC patients for measurement of TGFβ1 mRNA expression levels We also assessed the plasma TGFβ1 levels of HBV patients without n = 94 or with HCC n = 136 and healthy subjects n = 120 In our study group the risk of HCC in Chinese patients with HBV infection was significantly lower with the TT genotypes than in those with the CC genotypes at position −509 of TGFβ1 gene P = 001 In addition in the case group patients with the CC genotype had a statistically significant higher median plasma TGFβ1 or liver tumor tissue TGFβ1 mRNA level compared with the individuals with the TT genotype However in a subsequent analysis of the association between this polymorphism and clinicopathological characteristics including tumor number size grade stage and invasiveness there was no significant difference in both the distribution of genotype or allelic frequency within HCC patients indicating that −509CT exchange in TGFβ1 gene may play an important role in the occurrence not the progression of HBVrelated HCC through influencing plasma concentrations of TGFβ1 or TGFβ1 mRNA expression of liver tumor tissue

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