ABSTRACT
OBJECTIVE: To evaluate the association between p53 codon 72 polymorphism (R72P) and the risk of colorectal liver metastases. METHODS: The p53 R72P genotype was identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 78 consecutive colorectal cancer patients with liver metastases and 214 age- and sex-matched cases with nonmetastatic colorectal cancer. RESULTS: The R allele of the p53 R72P polymorphism was more frequently found in metastatic cases than in nonmetastatic cases (P=0.075). Carriers of the 72R allele had a 2.25-fold (95% CI (confidence interval)=1.05 to approximately 4.83) increased risk of liver metastases. On the stratification analysis, 72R-carrying genotype conferred a 3.46-fold (95% CI=1.02 to approximately 11.72) and a 1.05-fold (95% CI=0.36 to approximately 3.08) increased risk of liver metastases for p53 overexpression-positive and negative colorectal cancers, respectively. CONCLUSION: These results demonstrate for the first time that the 72R allele of the p53 polymorphism has an increased risk for liver metastases in colorectal cancers positive for p53 overexpression.
Subject(s)
Adenocarcinoma/genetics , Adenocarcinoma/secondary , Colorectal Neoplasms/genetics , Genes, p53 , Liver Neoplasms/genetics , Liver Neoplasms/secondary , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Case-Control Studies , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , DNA, Neoplasm/blood , DNA, Neoplasm/genetics , Female , Genetic Predisposition to Disease , Genotype , Humans , Liver Neoplasms/metabolism , Logistic Models , Male , Middle Aged , Multivariate Analysis , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Polymorphism, Single Nucleotide , Tumor Suppressor Protein p53/biosynthesis , Tumor Suppressor Protein p53/geneticsABSTRACT
OBJECTIVE: To investigate the association between the single nucleotide polymorphisms (SNPs) in TP53 gene and susceptibility to colorectal cancer (CRC) in Chinese population. METHODS: Peripheral blood samples were collected and white cell genomic DNA was extracted from 345 CRC patients, 198 males and 1447 females, aged (58.7 +/- 13.5), and 670 sex, age, smoking and drinking situations-matched controls in Ningbo city, Zhejiang province The genotypes of the SNPs of C-8343G, C-1863T, and R72P in TP53 gene were determined by either TaqMan assays or PCR-based restriction fragment length polymorphism method. Unconditional logistic regression was used to calculate the odds ratio (OR) for CRC after adjustment of the covariates, such as sex, age, cigarette smoking, alcohol drinking, body mass index and first-degree family history of CRC, and 95% confidence intervals (CI) so as to evaluate relative risk. RESULTS: There were not significant differences in the above mentioned covariates between these 2 groups. No significant association of C-8343G or C-1863T polymorphism with CRC risk was observed (both P > 0.05). The CRC risk of the 72P genotype was 50.3%, 1.53 times that of the 72R genotype (39.6%) (95% CI = 1.27 - 1.85, P < 0.01). The CRC risk of the RP heterozygotes was 1.60 times that of the RP homozygote (95% CI = 1.17 - 2.18, P < 0.01), and the CRC risk of the PP homozygotes was 2.37 times that of the RP heterozygotes (95% CI = 1.61 - 3.47, P < 0.01). A dose-response relationship was shown (P < 0.01). Stratified analysis indicated that the 72P allele conferred a more pronounced increase in CRC risk among the alcohol consumers: the CRC risk was 3.01 times for the RP heterozygotes (95% CI = 1.48 - 6.12), and 4.71 times for the PP homozygotes (95% CI = 1.90 - 11.68). CONCLUSION: TP53 C-8343G and C-1863T polymorphisms are not associated with CRC risk. R72P polymorphism contributes to the etiology of CRC in the Chinese population, particularly among the alcohol consumers.
Subject(s)
Asian People/genetics , Colorectal Neoplasms/genetics , Polymorphism, Single Nucleotide , Tumor Suppressor Protein p53/genetics , Adult , Aged , Aged, 80 and over , Alcohol Drinking , Alleles , China , Colorectal Neoplasms/ethnology , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Logistic Models , Male , Middle Aged , Risk Factors , SmokingABSTRACT
A TP53 gene polymorphism, resulting in an arginine (R) to proline (P) at codon 72 (TP53 R72P), has been associated with the susceptibility to various cancers. To better understand the role of this polymorphism in colorectal cancer etiology, we examined the association between TP53 R72P and colorectal cancer risk in 345 patients with colorectal cancer and 670 controls in a Chinese population. We observed that subjects with RP and PP genotypes had a 1.60-fold and a 2.37-fold increased risk for colorectal cancer, respectively. The 72P allele conferred a more pronounced increase in colorectal cancer risk among alcohol consumers (heterozygotes: OR = 3.01; homozygotes: OR = 4.71). The TP53 R72P polymorphism was not linked to tumor location, histologic grade, lymph node metastases, Dukes stage, p53 positivity, or age at diagnosis, but to tumor size. We conclude that the TP53 R72P polymorphism may contribute to the etiology of colorectal cancer in the Chinese population, particularly among alcohol consumers.
