Epidermal growth factor rs4444903 polymorphism and risk of cholangiocarcinoma. A case control study.

Aim of the study: Cholangiocarcinoma (CCA) comprises a diverse group of malignancies that occur anywhere along the biliary tree. Gene polymorphisms are risk factors for CCA development. Expression levels of epidermal growth factor (EGF) are correlated with progressive tumor growth and metastasis by increasing tumor cell proliferation and migration. The EGF rs4444903 (G) allele seems to enhance carcinogenesis in several types of cancer. The aim was to study the association between epidermal growth factor EGF (rs4444903) gene polymorphism and risk of CCA in Egyptian patients.

Material and methods: This case-control study included 100 subjects, 50 CCA patients and 50 healthy individuals as controls. The EGF (rs4444903) genotyping was performed by real-time polymerase chain reaction (PCR).

Results: The risk of CCA increased more in subjects with GG and AG genotypes than in those with AA genotype compared to the control group (p = 0.009, 0.037, OR = 4.20, 2.83, 95% CI: 1.40-12.60, 1.05-7.60 respectively). The variant G allele showed a highly significant association with CCA risk in the dominant model (p = 0.009). However, in the recessive model the G allele showed a nonsignificant association with the risk of CCA (p = 0.075). There were no significant differences between the EGF rs4444903 SNP genotypes in terms of the size of foci and presence of chronic hepatitis C virus (HCV) infection in the CCA group (p = 0.220, 0.645, respectively).

Conclusions: EGF rs4444903 polymorphism may have a role in the pathogenesis of CCA and the minor G allele may predispose to CCA, but it has no effect on severity of the disease.