A 40-bp insertion/deletion polymorphism in the constitutive promoter of MDM2 confers risk for hepatocellular carcinoma in a Chinese population

The pathogenesis of HCC is a multistage process with the involvement of genetic factors. The aim of the present study is to investigate the possible association between a 40-bp insertion/deletion polymorphism (indel) at constitutive promoter of MDM2 and risk of hepatocellular carcinoma (HCC) in a Chinese population. Using 420 HCC patients and 423 control subjects, we genotyped the indel polymorphism (rs3730485) using polymerase chain reaction method. Logistic regression was used to analyze the association between the polymorphism and HCC susceptibility. Under co-dominant model, we found that the ins/del and del/del genotype of indel was associated with a significantly increased risk of HCC compared with its homozygote ins/ins (OR = 1.39, 95%C.I. = 1.03–1.87; OR = 1.68, 95%C.I. = 1.03–2.73, respectively). Presence of 40-bp deletion allele of MDM2 seemed to confer higher risk for HCC when compared with non-carriers (OR = 1.30, 95%C.I. = 1.06–1.60, P = 0.011). Further stratification analysis showed that this association was more pronounced in patients with a family history of HCC, early tumor stage and higher serum alpha-fetoprotein (AFP). These findings indicated that the MDM2 indel polymorphism may be a genetic modifier for developing HCC in Chinese population.

► The 40-bp indel polymorphism within MDM2 is associated with the occurrence of HCC.
► The association is more pronounced in patients with early tumor stage.
► rs3730485 is associated with elevated serum AFP level (≥ 400 μg/L) of HCC patients.