Die Sequenzvarianten Arg72Pro des Tumorsuppressorgens p53 und Arg462Gln des Prostatakarzinom-Suszeptibilitätsgens RNASEL haben einen additiven Effekt auf das Erkrankungsalter von HNPCC-Patienten

摘要: p53 and the prostate-cancer-susceptibility gene RNASEL are tumour suppressor genes involved in apoptosis. We have previously reported that common, functionally different variants Arg72Pro Arg462Gln associated with age of disease onset colorectal cancer Lynch syndrome patients. To assess combined effect both variants, we screened 246 unrelated patients a pathogenic germline mutation either MSH2 (n = 138) or MLH1 108) as first tumour, 245 healthy controls. The global log rank test revealed significant differences for genotypes each variant (p 0.0176 p 0.0358 RNASEL) 0.0174). highest difference median was seen between homozygotes wildtypes (42 years [range 22–75]) alleles (30 26–47]). A multivariate Cox regression model indicated only had influence on 0.016 0.014 an additive mode inheritance, effects purely additive, which supports notion RNase L pathways do not interact. These findings may be relevant preventive strategies syndrome.