A TP53 polymorphism is associated with increased risk of colorectal cancer and with reduced levels of TP53 mRNA

Oncogene. 2004 Mar 11;23(10):1954-6. doi: 10.1038/sj.onc.1207305.


We undertook a case-control study to examine the possible associations of the TP53 variants Arg > Pro at codon 72 and p53PIN3, a 16 bp insertion/duplication in intron 3, with the risk of colorectal cancer (CRC). The p53PIN3 A2 allele (16 bp duplication) was associated with an increased risk (OR 1.55, 95% CI 1.10-2.18, P = 0.012), of the same order of magnitude as that observed in previous studies for other types of cancer. The Pro72 allele was weakly associated with CRC (OR = 1.34, 95% CI 0.98-1.84, P = 0.066). The possible functional role of p53PIN3 was investigated by examining the TP53 mRNA transcripts in 15 lymphoblastoid cell lines with different genotypes. The possibility that the insertion/deletion could lead to alternatively spliced mRNAs was excluded. However, we found reduced levels of TP53 mRNA associated with the A2 allele. In conclusion, the epidemiological study suggests a role for p53PIN3 in tumorigenesis, supported by the in vitro characterization of this variant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Base Sequence
  • Case-Control Studies
  • Codon / genetics*
  • Colorectal Neoplasms / epidemiology*
  • Colorectal Neoplasms / genetics*
  • Exons
  • Genes, p53 / genetics*
  • Humans
  • Introns / genetics
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide*
  • RNA, Messenger / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
  • Transcription, Genetic


  • Codon
  • RNA, Messenger