TP53 R72P and MDM2 SNP309 polymorphisms and colorectal cancer risk: the Fukuoka Colorectal Cancer Study.
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.
Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. amitman@phealth.med.kyushu-u.ac.jp
Amit Man
AM
Joshi
Sanjeev
S
Budhathoki
Keizo
K
Ohnaka
Ryuichi
R
Mibu
Masao
M
Tanaka
Yoshihiro
Y
Kakeji
Yoshihiko
Y
Maehara
Takeshi
T
Okamura
Koji
K
Ikejiri
Kitaroh
K
Futami
Takafumi
T
Maekawa
Yohichi
Y
Yasunami
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*
C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2