Cancer Risks for MLH1 and MSH2 Mutation Carriers

ABSTRACT We studied 17,576 members of 166 MLH1 and 224 MSH2 mutation‐carrying families from the Colon Cancer Family Registry. Average cumulative risks of colorectal cancer (CRC), endometrial cancer (EC), and other cancers for carriers were estimated using modified segregation analysis conditioned on...

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Bibliographic Details
Published in:Human mutation 2013-03, Vol.34 (3), p.490-497
Main Authors: Dowty, James G., Win, Aung K., Buchanan, Daniel D., Lindor, Noralane M., Macrae, Finlay A., Clendenning, Mark, Antill, Yoland C., Thibodeau, Stephen N., Casey, Graham, Gallinger, Steve, Marchand, Loic Le, Newcomb, Polly A., Haile, Robert W., Young, Graeme P., James, Paul A., Giles, Graham G., Gunawardena, Shanaka R., Leggett, Barbara A., Gattas, Michael, Boussioutas, Alex, Ahnen, Dennis J., Baron, John A., Parry, Susan, Goldblatt, Jack, Young, Joanne P., Hopper, John L., Jenkins, Mark A.
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - genetics
Adult
Age Factors
Aged
Aged, 80 and over
cancer
Carrier Proteins - genetics
Carrier Proteins - metabolism
Colon CFR
colorectal cancer
Colorectal Neoplasms - genetics
Colorectal Neoplasms, Hereditary Nonpolyposis - genetics
endometrial cancer
Endometrial Neoplasms - genetics
Female
Germ-Line Mutation
Heterozygote
Humans
Lynch syndrome
Male
Middle Aged
MLH1
MSH2
MutL Protein Homolog 1
MutS Homolog 2 Protein - genetics
Nuclear Proteins - genetics
Penetrance
risk
Risk Factors
segregation analysis
Surveys and Questionnaires
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Summary:ABSTRACT We studied 17,576 members of 166 MLH1 and 224 MSH2 mutation‐carrying families from the Colon Cancer Family Registry. Average cumulative risks of colorectal cancer (CRC), endometrial cancer (EC), and other cancers for carriers were estimated using modified segregation analysis conditioned on ascertainment criteria. Heterogeneity in risks was investigated using a polygenic risk modifier. Average CRC cumulative risks at the age of 70 years (95% confidence intervals) for MLH1 and MSH2 mutation carriers, respectively, were estimated to be 34% (25%–50%) and 47% (36%–60%) for male carriers and 36% (25%–51%) and 37% (27%–50%) for female carriers. Corresponding EC risks were 18% (9.1%–34%) and 30% (18%–45%). A high level of CRC risk heterogeneity was observed (P 
ISSN:1059-7794
1098-1004
DOI:10.1002/humu.22262