Polymorphisms in TP53 and MDM2 contribute to higher risk of colorectal cancer in Chinese population: a hospital-based, case–control study
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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.
KeywordsTP53 MDM2 Polymorphism Colorectal cancer
This work was supported by the project of the Ministry of Finance and Health of China (2009–193, Jigui Chen, principal investigator), the National Natural Science Foundation of China (NSFC-30972534 and NSFC-81172752, Shaofa Nie, principal investigator). We thank all the patients and controls participated in this study for their cooperation and Chang Liu (Department of Surgery, The Eighth Hospital of Wuhan City) for her effort in collection of clinical samples and epidemiological data.
Conflict of interests
There is no conflict of interests.
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