Association between MDM2-SNP309 and age at colorectal cancer diagnosis according to p53 mutation status.
A single-nucleotide polymorphism (SNP) in the promoter of the MDM2 gene, SNP309 (a T-->G change), was recently implicated in the early onset of cancer in individuals with Li-Fraumeni syndrome and of sporadic soft-tissue sarcoma. SNP309 induces an increase in the level of Mdm2 protein, which causes attenuation of the p53 pathway. To investigate the effect of this polymorphism in colorectal cancer pathogenesis, we genotyped 153 colorectal cancer patients who were randomly selected from among 330 consecutive patients stratified according to p53 mutation status and age at diagnosis, for alleles of MDM2-SNP309. Among the 77 patients with p53 wild-type tumors, the median age at colorectal cancer diagnosis was 71.5 years for patients with the T/T genotype and 61.0 years for patients with SNP309 (T/G or G/G genotype) (estimated difference between medians [Hodges-Lehmann method] = 8.0 years, 95% confidence interval = 1.0 to 16.0 years; P = .03 [two-sided Wilcoxon rank sum test]). Our data indicate that MDM2-SNP309 is a modifier of the age at colorectal cancer onset for patients whose tumors have a wild-type p53 gene.
Menin
Chiara
C
IST-Genova, Azienda Ospedaliera di Padova and Istituto Oncologico Veneto, Padova, Italy.
Scaini
Maria Chiara
MC
De Salvo
Gian Luca
GL
Biscuola
Martina
M
Quaggio
Monica
M
Esposito
Giovanni
G
Belluco
Claudio
C
Montagna
Marco
M
Agata
Simona
S
D'Andrea
Emma
E
Nitti
Donato
D
Amadori
Alberto
A
Bertorelle
Roberta
R
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D016158:Genes, p53; D005838:Genotype; D005998:Glycine; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D013912:Threonine
D013912:Threonine; D051736:Proto-Oncogene Proteins c-mdm2; D005998:Glycine