Genetic variants in germline TP53 and MDM2 SNP309 are not associated with early onset colorectal cancer.
OBJECTIVE
Colorectal cancer (CRC) arising in patients under age 30 is a rare disease, and few cases have been reported within Li-Fraumeni kindreds. To determine how often alterations in the p53 pathway genes contribute to disease susceptibility, we have evaluated patients with early onset CRC for the presence of germline variants in the p53 gene and MDM2 SNP309.


METHODS
Thirty-five patients with CRC diagnosed before age 30 were included in this study-based on tissue availability. DNA samples from peripheral blood leukocytes were analyzed for constitutional mutations and polymorphisms in p53 as well as polymorphisms in MDM2 SNP309.


RESULTS
No mutations were found in exons 4-10 of the p53 gene. The frequencies of polymorphisms in p53 and in MDM2 SNP309 did not differ from rates previously reported for normal control populations, and no polymorphism in either gene could be associated with early onset CRC.


CONCLUSIONS
Neither germline variants in p53 nor MDM2 SNP309 play an underlying role in the development of very early onset CRC. For the large majority of cases, the genetic basis of this disease remains unknown.
Khan
Sajid A
SA
Colorectal Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Idrees
Kamran
K
Forslund
Ann
A
Zeng
Zhaoshi
Z
Rosenberg
Shoshana
S
Pincas
Hanna
H
Barany
Francis
F
Offit
Kenneth
K
Laquaglia
Michael P
MP
Paty
Philip B
PB
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2