Genetic variants in germline TP53 and MDM2 SNP309 are not associated with early onset colorectal cancer

Abstract

Background and objectives: 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.

Fig. 1

Temporal temperature gradient electrophoresis (TTGE) gel for TP53 exon 6 showing normal and aberrantly migrating bands. All patients possess wild-type bands while patient 6 possesses an additional aberrantly migrating band. Subsequesnt dideoxy sequencing revealed this band to represent a polymorphism in codon 213. Cell lines LoVo and BxPc3 are wild-type and mutant controls, respectively.

Fig. 2

Electropherogram displaying possible genotypes for MDM2 SNP309. The possible genotypes shown are T/G, G/G, and T/T.