title: 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: Department of Surgery, The Eighth Hospital of Wuhan City, No. 1307 of Zhongshan Avenue, Wuhan 430000, China.
authors: Yuxing
authors: Y
authors: Zhang
authors: Li
authors: L
authors: Liu
authors: Yingchun
authors: Y
authors: Tang
authors: Chao
authors: C
authors: Chen
authors: Qian
authors: Q
authors: Wang
authors: Jun
authors: J
authors: Xu
authors: Chao
authors: C
authors: Yang
authors: Xiaoping
authors: X
authors: Miao
authors: Sheng
authors: S
authors: Wei
authors: Jigui
authors: J
authors: Chen
authors: Shaofa
authors: S
authors: Nie
mesh_terms: D000368:Aged; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D002681:China; D015179:Colorectal Neoplasms / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006773:Hospitals, Municipal; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2