Objective: The tumor suppressor p53 pathway plays a crucial role in preventing carcinogenesis through its ability to impose cell cycle arrest and apoptosis following DNA damage or oncogene activation. Mouse double minute 2 (MDM2) gene is a key negative regulator of p53 pathway and overexpressed in many cancers as oncoprotein. We have previously shown that genetic polymorphisms in the MDM2 promoter (309T --> G) and p53 coding region (72Arg --> Pro) are associated with susceptibility to esophageal and lung cancers. This study investigated the associations between these polymorphisms in p53 and MDM2 and risk of the occurrence and progression of colorectal cancer.
Methods: Genotypes of 1000 Chinese colorectal cancer patients and 1300 controls were determined by PCR-based restriction fragment length polymorphism or tetra-primer amplification refractory mutation system-PCR. Associations with risk of colorectal cancer were estimated by unconditional logistic regression.
Results: An increased colorectal cancer risk associated with the MDM2 GG [odds ratio (OR) = 2.06, 95% confidence interval (CI) = 1.62-2.62] or TG (OR = 1.31, 95% CI = 1.06-1.62) genotype was observed compared with the TT genotype. No association was found between p53 polymorphism and risk of the cancer, with the ORs being 0.87 (95% CI = 0.68-1.11) for the Pro/Pro and 0. 85 (95% CI = 0.70-1.04) for the Arg/Pro genotype compared with the Arg/Arg genotype. However, combined analysis of MDM2 and p53 polymorphisms showed that compared with subjects carrying both MDM2 TT and p53 Arg/Arg genotypes, the OR for subjects carrying both MDM2 GG and p53 Pro/Pro genotypes was 2.75 (95% CI = 1.60-4.70), significantly higher than that for subjects carrying both MDM2 TT and p53 Pro/Pro genotypes (OR = 1.09, 95% CI = 0.63-1.88).
Conclusion: These results suggest that genetic polymorphism in MDM2 may be associated with susceptibility to colorectal cancer in a Chinese population.