HapMap-based study of CIP2A gene polymorphisms and HCC susceptibility

Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001.
Oncology letters (Impact Factor: 1.55). 08/2012; 4(2):358-364. DOI: 10.3892/ol.2012.728
Source: PubMed


CIP2A is a human oncoprotein that inhibits PP2A and stabilizes c-myc in human malignancies. Autoantibodies to CIP2A protein have been reported to be present in higher levels in sera from patients with hepatocellular carcinoma (HCC) than in sera of healthy individuals. The CIP2A gene has been demonstrated as a potential cancer susceptibility gene. To elucidate whether common CIP2A variants are associated with HCC susceptibility, we conducted a case-control study comprising 233 cases of HCC and 280 controls matched on age, gender and ethnicity in the Chinese Han population. Two haplotype-tagging single nucleotide polymorphisms (htSNPs) (rs2278911 and rs4855656) from the HapMap database were analyzed, which provide an almost complete coverage of the genetic variations in the CIP2A gene. We found that neither of these htSNPs and haplotypes were associated with the risk of HCC. However, an interaction was observed between hepatitis virus B and C infection (HBV and HCV) and the C carriers (TC or CC) of rs2278911 on HCC risk (OR=12.35; 95% CI, 4.93-19.87). No such association was found for rs4855656. Our study also demonstrated that two htSNPs (rs2278911 and rs4855656) in the CIP2A gene are not associated with the risk of HCC. HBV and HCV infection was found to exert a synergistic effect on the risk of HCC in individuals with the C carriers (TC or CC) of rs2278911 in the Chinese Han population.

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    • "The wild-type has a positively charged area around Arg229 with a small inward protruding cavity next to Arg229 (Fig. 7A) whereas the corresponding area is considerably less charged in the Arg229Gln mutant and the inward protruding cavity is bigger (Fig. 7B). Coupling these results to the conclusions drawn by Li et al., 2012 suggests that the positive charge and shape of this surface area are important for the expression and function of CIP2A, and this area is possibly involved in the protein–protein complexes formed between CIP2A and other proteins, for example other oncoproteins. "
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