A TP53 polymorphism is associated with increased risk of colorectal cancer and with reduced levels of TP53 mRNA
2003; Springer Nature; Volume: 23; Issue: 10 Linguagem: Inglês
10.1038/sj.onc.1207305
ISSN1476-5594
AutoresFederica Gemignani, Vı́ctor Moreno, Stefano Landi, Norman Moullan, Amélie Chabrier, Sara Gutiérrez‐Enríquez, Janet Hall, Elisabet Guinó, Miguel A. Peinado, Gabriel Capellà, Federico Canzian,
Tópico(s)Cancer Genomics and Diagnostics
ResumoWe 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.
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