title: Genetic variants in germline TP53 and MDM2 SNP309 are not associated with early onset colorectal cancer.
abstract: 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.
authors.affiliation: Colorectal Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Sajid A
authors.initials: SA
authors.lastname: Khan
authors.forename: Kamran
authors.initials: K
authors.lastname: Idrees
authors.forename: Ann
authors.initials: A
authors.lastname: Forslund
authors.forename: Zhaoshi
authors.initials: Z
authors.lastname: Zeng
authors.forename: Shoshana
authors.initials: S
authors.lastname: Rosenberg
authors.forename: Hanna
authors.initials: H
authors.lastname: Pincas
authors.forename: Francis
authors.initials: F
authors.lastname: Barany
authors.forename: Kenneth
authors.initials: K
authors.lastname: Offit
authors.forename: Michael P
authors.initials: MP
authors.lastname: Laquaglia
authors.forename: Philip B
authors.initials: PB
authors.lastname: Paty
mesh_terms: 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*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2