Cumulative incidence of colorectal and extracolonic cancers in MLH1 and MSH2 mutation carriers of hereditary nonpolyposis colorectal cancer

The Clinical Phenotype of Lynch Syndrome Due to Germ-Line PMS2 Mutations

“…There have been numerous other studies estimating penetrance for LS-associated cancers for MLH1 and MSH2 mutation carriers to be even higher, however the majority were based on families that were ascertained because they had striking clinical histories and as penetrance estimates were not conditioned on this ascertainment, the previous estimates were upwardly biased. 9,44,45 If the risks of cancer for PMS2 mutation carriers are lower than that for carriers of mutations in other mismatch repair genes, which is consistent with the observed data, the molecular explanation for this is unclear. It has been hypothesized that MLH1 can form a heterodimer with MLH3 or PMS1 in the absence of functional PMS2, which may compensate for the MutLα heterodimer in the mismatch repair process.…”

Phenotypic and genotypic heterogeneity in the Lynch syndrome: diagnostic, surveillance and management implications

“…Individuals with such mutations have an E70% -85% risk, based on the mutation's penetrance, to develop CRC by the age of 60 years. 33 A subset of MMR germline mutations involving large deletions of entire exons are often unidentifiable using regular testing techniques. However, they can be found through various alternative techniques such as those used to identify the already-mentioned MSH2 exon 1 -6 deletion.…”

Estimating cancer risk in HNPCC by the GRL method

“…Most studies estimate the risk of colorectal cancer in families with HNPCC syndrome selected according to Amsterdam criteria without correcting for selection bias [4][5][6][7][8][9] . Estimates in these studies range from 0.68 to 0.82, but these values have been shown to be substantially overestimated 10 .…”