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Cancer risks and immunohistochemical profiles linked to the Danish MLH1 Lynch syndrome founder mutation

Therkildsen, Christina; Isinger-Ekstrand, Anna; Ladelund, Steen; Nissen, Anja; Rambech, Eva LU ; Bernstein, Inge and Nilbert, Mef LU (2012) In Familial Cancer 11(4). p.579-585
Abstract
Founder mutations with a large impact in distinct populations have been described in Lynch syndrome. In Denmark, the MLH1 c.1667+2_1667_+8TAAATCAdelinsATTT mutation accounts for 25 % of the MLH1 mutant families. We used the national Danish hereditary nonpolyposis colorectal cancer register to estimate the cumulative lifetime risks for Lynch syndrome-associated cancer in 16 founder mutation families with comparison to 47 other MLH1 mutant families. The founder mutation conferred comparable risks for colorectal cancer (relative risks, RR, of 0.99 for males and 0.79 for females) and lower risks for extracolonic cancer (RR of 0.69 for endometrial cancer and 0.39 for all other extracolonic cancers). We also characterized expression of key... (More)
Founder mutations with a large impact in distinct populations have been described in Lynch syndrome. In Denmark, the MLH1 c.1667+2_1667_+8TAAATCAdelinsATTT mutation accounts for 25 % of the MLH1 mutant families. We used the national Danish hereditary nonpolyposis colorectal cancer register to estimate the cumulative lifetime risks for Lynch syndrome-associated cancer in 16 founder mutation families with comparison to 47 other MLH1 mutant families. The founder mutation conferred comparable risks for colorectal cancer (relative risks, RR, of 0.99 for males and 0.79 for females) and lower risks for extracolonic cancer (RR of 0.69 for endometrial cancer and 0.39 for all other extracolonic cancers). We also characterized expression of key Wnt-signaling proteins in colorectal cancers with the founder mutation. Aberrant staining affected beta-catenin in 59 %, E-cadherin in 68 %, TCF-4 in 94 % and Cyclin D1 in 68 % with extensive inter-tumor variability despite the same underlying germline mutation. In conclusion, the Danish MLH1 founder mutation that accounts for a significant proportion of Lynch syndrome and is associated with a lower risk for extracolonic cancers. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
HNPCC, Mismatch repair, Colorectal cancer, Endometrial cancer, Cumulative risk, Wnt-signaling
in
Familial Cancer
volume
11
issue
4
pages
579 - 585
publisher
Kluwer
external identifiers
  • wos:000310467300006
  • scopus:84870413516
ISSN
1389-9600
DOI
10.1007/s10689-012-9552-4
language
English
LU publication?
yes
id
eb8ceaf9-4a75-4b29-ac30-a652d9ade0f4 (old id 3283388)
date added to LUP
2013-01-07 09:40:43
date last changed
2017-01-01 03:26:11
@article{eb8ceaf9-4a75-4b29-ac30-a652d9ade0f4,
  abstract     = {Founder mutations with a large impact in distinct populations have been described in Lynch syndrome. In Denmark, the MLH1 c.1667+2_1667_+8TAAATCAdelinsATTT mutation accounts for 25 % of the MLH1 mutant families. We used the national Danish hereditary nonpolyposis colorectal cancer register to estimate the cumulative lifetime risks for Lynch syndrome-associated cancer in 16 founder mutation families with comparison to 47 other MLH1 mutant families. The founder mutation conferred comparable risks for colorectal cancer (relative risks, RR, of 0.99 for males and 0.79 for females) and lower risks for extracolonic cancer (RR of 0.69 for endometrial cancer and 0.39 for all other extracolonic cancers). We also characterized expression of key Wnt-signaling proteins in colorectal cancers with the founder mutation. Aberrant staining affected beta-catenin in 59 %, E-cadherin in 68 %, TCF-4 in 94 % and Cyclin D1 in 68 % with extensive inter-tumor variability despite the same underlying germline mutation. In conclusion, the Danish MLH1 founder mutation that accounts for a significant proportion of Lynch syndrome and is associated with a lower risk for extracolonic cancers.},
  author       = {Therkildsen, Christina and Isinger-Ekstrand, Anna and Ladelund, Steen and Nissen, Anja and Rambech, Eva and Bernstein, Inge and Nilbert, Mef},
  issn         = {1389-9600},
  keyword      = {HNPCC,Mismatch repair,Colorectal cancer,Endometrial cancer,Cumulative risk,Wnt-signaling},
  language     = {eng},
  number       = {4},
  pages        = {579--585},
  publisher    = {Kluwer},
  series       = {Familial Cancer},
  title        = {Cancer risks and immunohistochemical profiles linked to the Danish MLH1 Lynch syndrome founder mutation},
  url          = {http://dx.doi.org/10.1007/s10689-012-9552-4},
  volume       = {11},
  year         = {2012},
}