Objective: Tumor protein p53 gene and its negative regulator, murine double minute 2 homolog are important components for cell-cycle arrest and apoptosis. An arginine-to-proline substitution at codon 72 in the p53 gene is reported to decrease apoptotic potential, while a thymine-to-guanine polymorphism at nucleotide 309, named SNP309, of murine double minute 2 gene increases transcription of the gene. These two polymorphisms therefore may be of importance in colorectal carcinogenesis. The relation of these polymorphisms to colorectal cancer risk was addressed in the Fukuoka Colorectal Cancer Study.
Methods: We genotyped the two polymorphisms in 685 incident cases of colorectal cancer and 778 community controls by the polymerase chain reaction-restriction fragment length polymorphism method. Statistical adjustment was made for sex and age.
Results: The proline allele of p53 gene and the guanine allele of SNP309 were each associated with a small, statistically non-significant increase in the odds ratio of colorectal cancer; the adjusted odds ratio (95% confidence interval) for arginine/proline and proline/proline genotypes combined versus arginine/arginine genotype of p53 gene was 1.23 (0.99-1.52) and that for thymine/guanine and guanine/guanine genotypes combined versus thymine/thymine genotype of SNP309 was 1.27 (0.98-1.63). Individuals harboring the proline allele of p53 gene and the guanine allele of SNP309 showed an odds ratio of 1.67 (95% confidence interval, 1.11-2.51).
Conclusions: Codon 72 polymorphism of p53 and SNP309 in combination may confer an increased risk of colorectal cancer.