The −149C>T SNP within the ΔDNMT3B gene, is not associated with early disease onset in hereditary non-polyposis colorectal cancer

Abstract

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominantly inherited syndrome caused by germline mutations in mismatch repair (MMR) genes. HNPCC patients have a lifetime risk of 80% of developing colorectal cancer (CRC); however the likely age of onset is difficult to predict. A single C>T polymorphism located within the promoter region of the ΔDNMT3B gene has recently been reported to be associated with a significant increase to the risk of early onset CRC. In this study we determined the ΔDNMT3B genotype in 404 confirmed HNPCC participants (total of 194 CRC cases) from Australia (203) and Poland (201). From the total number of participants there were 194 diagnosed cases of CRC and 210 healthy MMR gene mutation carriers. The study was undertaken to assess whether the reported effect observed in a previous study of 146 HNPCC patients is consistent in a larger separate and unrelated participant cohort. Through the statistical tests of Kaplan–Meier survival analysis and Cox hazard regression models we did not observe any significant association between the ΔDNMT3B C>T SNP and early onset CRC in HNPCC patients.