A TP53 polymorphism is associated with increased risk of colorectal cancer and with reduced levels of TP53 mRNA.
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.
Gemignani
Federica
F
International Agency for Research on Cancer, Lyon 69372, France.
Moreno
Victor
V
Landi
Stefano
S
Moullan
Norman
N
Chabrier
Amélie
A
Gutiérrez-Enríquez
Sara
S
Hall
Janet
J
Guino
Elisabeth
E
Peinado
Miguel Angel
MA
Capella
Gabriel
G
Canzian
Federico
F
D019943:Amino Acid Substitution; D001483:Base Sequence; D016022:Case-Control Studies; D003062:Codon / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D005091:Exons; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D014158:Transcription, Genetic
D003062:Codon; D012333:RNA, Messenger