Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome

Win, Aung Ko, Lindor, Noralane M., Young, Joanne P., Macrae, Finlay A., Young, Graeme P., Williamson, Elizabeth, Parry, Susan, Goldblatt, Jack, Lipton, Lara, Winship, Ingrid, Leggett, Barbara, Tucker, Katherine M., Giles, Graham G., Buchanan, Daniel D., Clendenning, Mark, Rosty, Christophe, Arnold, Julie, Levine, A. Joan, Haile, Robert W., Gallinger, Steven, Le Marchand, Loic, Newcomb, Polly A., Hopper, John L. and Jenkins, Mark A. (2012) Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome. Journal of the National Cancer Institute, 104 18: 1363-1372. doi:10.1093/jnci/djs351

Author Win, Aung Ko
Lindor, Noralane M.
Young, Joanne P.
Macrae, Finlay A.
Young, Graeme P.
Williamson, Elizabeth
Parry, Susan
Goldblatt, Jack
Lipton, Lara
Winship, Ingrid
Leggett, Barbara
Tucker, Katherine M.
Giles, Graham G.
Buchanan, Daniel D.
Clendenning, Mark
Rosty, Christophe
Arnold, Julie
Levine, A. Joan
Haile, Robert W.
Gallinger, Steven
Le Marchand, Loic
Newcomb, Polly A.
Hopper, John L.
Jenkins, Mark A.
Title Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome
Journal name Journal of the National Cancer Institute   Check publisher's open access policy
ISSN 0027-8874
Publication date 2012-09-19
Sub-type Article (original research)
DOI 10.1093/jnci/djs351
Open Access Status DOI
Volume 104
Issue 18
Start page 1363
End page 1372
Total pages 10
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Abstract Tumor testing of colorectal cancers (CRC) for mismatch repair (MMR) deficiency is an effective approach to identify carriers of germline MMR gene mutation (Lynch syndrome). The aim of this study was to identify MMR gene mutation carriers in two cohorts of population-based CRC utilizing a combination of tumor and germline testing approaches.
Formatted abstract
Background Lynch syndrome is a highly penetrant cancer predisposition syndrome caused by germline mutations in DNA mismatch repair (MMR) genes. We estimated the risks of primary cancers other than colorectal cancer following a diagnosis of colorectal cancer in mutation carriers.
Methods We obtained data from the Colon Cancer Family Registry for 764 carriers of an MMR gene mutation (316 MLH1, 357 MSH2, 49 MSH6, and 42 PMS2), who had a previous diagnosis of colorectal cancer. The Kaplan–Meier method was used to estimate their cumulative risk of cancers 10 and 20 years after colorectal cancer. We estimated the age-, sex-, country- and calendar period–specific standardized incidence ratios (SIRs) of cancers following colorectal cancer, compared with the general population.
Results Following colorectal cancer, carriers of MMR gene mutations had the following 10-year risk of cancers in other organs: kidney, renal pelvis, ureter, and bladder (2%, 95% confidence interval [CI] = 1% to 3%); small intestine, stomach, and hepatobiliary tract (1%, 95% CI = 0.2% to 2%); prostate (3%, 95% CI = 1% to 5%); endometrium (12%, 95% CI = 8% to 17%); breast (2%, 95% CI = 1% to 4%); and ovary (1%, 95% CI = 0% to 2%). They were at elevated risk compared with the general population: cancers of the kidney, renal pelvis, and ureter (SIR = 12.54, 95% CI = 7.97 to 17.94), urinary bladder (SIR = 7.22, 95% CI = 4.08 to 10.99), small intestine (SIR = 72.68, 95% CI = 39.95 to 111.29), stomach (SIR = 5.65, 95% CI = 2.32 to 9.69), and hepatobiliary tract (SIR = 5.94, 95% CI = 1.81 to 10.94) for both sexes; cancer of the prostate (SIR = 2.05, 95% CI = 1.23 to 3.01), endometrium (SIR = 40.23, 95% CI = 27.91 to 56.06), breast (SIR = 1.76, 95% CI = 1.07 to 2.59), and ovary (SIR = 4.19, 95% CI = 1.28 to 7.97).
Conclusion Carriers of MMR gene mutations who have already had a colorectal cancer are at increased risk of a greater range of cancers than the recognized spectrum of Lynch syndrome cancers, including breast and prostate cancers.
Keyword Colorectal cancer
Lynch syndrome
microsatellite instability, MLH1, MSH2, MSH6, PMS2, MLH1 methylation, BRAFV600E
mismatch repair protein expression
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID U01 CA097735
U24 CA097735
UM1 CA167551
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Medicine Publications
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