Polymorphisms in TP53 and MDM2 contribute to higher risk of colorectal cancer in Chinese population: a hospital-based, case-control study.

Abstract

The murine double minute 2 protein (MDM2) and TP53 interact in regulating cell cycle, DNA repair and apoptosis process, which is crucial in carcinogenesis. Since functional variations in these two genes were shown to change gene expression and function, we hypothesized that potentially functional polymorphisms in these genes may contribute to colorectal cancer (CRC) susceptibility. A hospital-based case-control study consisting of 444 patients and 569 controls was conducted to explore the associations between TP53 Arg72Pro and MDM2 T309G and CRC risk in Chinese. The combined effect of TP53 Arg72Pro and MDM2 T309G was significant in a gene dose-response increasing CRC risk (trend test: P = 0.02). Individuals carrying 3 or more potential risk alleles had 1.78 times risk (95 % CI: 1.13-2.80) to develop CRC compared with individuals without potential risk allele. This increased cancer risk was more pronounced in smokers who carried 3-4 potential risk alleles (OR = 2.75, 95 % CI: 1.14-6.60) and in young subjects (OR = 2.05, 95 % CI: 1.08-3.88). The gene-gene interaction between TP53 Arg72Pro and MDM2 T309G may interact in carcinogenesis of CRC in Chinese, especially in smokers, and this kind of interaction is associated with onset age of CRC.

• Authors: Yuxing Zhang, Li Liu, Yingchun Tang, Chao Chen, Qian Wang, Jun Xu, Chao Yang, Xiaoping Miao, Sheng Wei, Jigui Chen, Shaofa Nie
• Journal: Molecular biology reports (Mol Biol Rep) Vol. 39 Issue 10 Pg. 9661-8 (Oct 2012) ISSN: 1573-4978 [Electronic] Netherlands
• PMID: 22744426 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• TP53 protein, human
• Tumor Suppressor Protein p53
• MDM2 protein, human
• Proto-Oncogene Proteins c-mdm2

Topics

• Aged
• Amino Acid Substitution
• Case-Control Studies
• China
• Colorectal Neoplasms (genetics)
• Epistasis, Genetic
• Female
• Gene Frequency
• Genetic Association Studies
• Genetic Predisposition to Disease
• Hospitals, Municipal
• Humans
• Logistic Models
• Male
• Middle Aged
• Multivariate Analysis
• Polymorphism, Single Nucleotide
• Proto-Oncogene Proteins c-mdm2 (genetics)
• Tumor Suppressor Protein p53 (genetics)