title: A TP53 polymorphism is associated with increased risk of colorectal cancer and with reduced levels of TP53 mRNA.
abstract: 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.
authors.affiliation: International Agency for Research on Cancer, Lyon 69372, France.
authors.forename: Federica
authors.initials: F
authors.lastname: Gemignani
authors.forename: Victor
authors.initials: V
authors.lastname: Moreno
authors.forename: Stefano
authors.initials: S
authors.lastname: Landi
authors.forename: Norman
authors.initials: N
authors.lastname: Moullan
authors.forename: Amélie
authors.initials: A
authors.lastname: Chabrier
authors.forename: Sara
authors.initials: S
authors.lastname: Gutiérrez-Enríquez
authors.forename: Janet
authors.initials: J
authors.lastname: Hall
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Guino
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Peinado
authors.forename: Gabriel
authors.initials: G
authors.lastname: Capella
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
mesh_terms: 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
chemical_list: D003062:Codon; D012333:RNA, Messenger