Association of a p73 exon 2 G4C14-to-A4T14 polymorphism with risk of hepatocellular carcinoma in a Chinese population

Abstract

P73, a p53 homolog, has some p53-like activities and plays an important role in modulating cell cycle, apoptosis, and DNA repair. A potentially functional dinucleotide polymorphism, G4C14-to-A4T14, has been identified in the 5' untranslated region of exon 2 of the p73 gene, which may theoretically form a stem-loop structure and affect gene expression. We hypothesized that genetic variants in p73 may modify individual susceptibility to hepatocellular carcinoma (HCC). To test this hypothesis that these two common variants play a role in HCC susceptibility, we conducted a hospital-based case-control study of 476 HCC patients and 526 cancer-free controls in a Chinese population. The matrix-assisted laser desorption ionization time-of-flight mass spectrometry method was performed to detect these polymorphisms. The results showed that the genotype and allele frequencies of the p73 G4C14-A4T14 did not differ significantly between the HCC patients and the control group (all P values are above 0.05). However, with stratification analysis by age, sex, smoking status, drinking status, HBV carrier state, and family history of cancer, we found that the variant genotypes (GC/AT + AT/AT) of the p73 G4C14-A4T14 was associated with a significant increased risk of HCC among HbsAg-positive individuals (adjusted OR = 2.19, 95% CI = 1.25-3.83) and among women (adjusted OR = 2.62, 95% CI = 1.47, 4.66). These results suggest that the p73 G4C14-to-A4T14 dinucleotide polymorphism may play a role in the development of chronic HBV-infected HCC in the Chinese population, especially among women.