The p53 codon 72 variation is associated with the age of onset of hereditary non-polyposis colorectal cancer (HNPCC)

摘要: The polymorphic variants at codon 72 of the p53 gene were shown to be functionally distinct in vitro, whereby arginine (arg) variant induces apoptosis more efficiently than proline (pro) variant. From evidence that DNA mismatch repair system and interact maintain genomic integrity, we hypothesized variation may influence age onset disease HNPCC patients. We tested 538 patients for variants, including 167 unrelated with pathogenic germline mutations MSH2 or MLH1 colorectal carcinoma as first tumour, 126 sporadic microsatellite stable cancers, 245 healthy controls. median was 41, 36, 32 years mutation carriers arg/arg, arg/pro, pro/pro genotypes, respectively. log rank test revealed significant differences between arg/arg individuals (p = 0.0002) arg/ pro versus 0.0026 p 0.0217, respectively). A Cox regression model indicated an additive mode inheritance. No observed among different genotype tumours. Our results suggest genotypes are associated a deficient background dose dependent manner. These findings relevant preventive strategies HNPCC.