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https://hdl.handle.net/2440/93554
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Type: | Journal article |
Title: | Risks of primary extracolonic cancers following colorectal cancer in Lynch syndrome |
Author: | Win, A. Lindor, N. Young, J. Macrae, F. Young, G. Williamson, E. Parry, S. Goldblatt, J. Lipton, L. Winship, I. Leggett, B. Tucker, K. Giles, G. Buchanan, D. Clendenning, M. Rosty, C. Arnold, J. Joan Levine, A. Haile, R. Gallinger, S. et al. |
Citation: | Journal of the National Cancer Institute, 2012; 104(18):1363-1372 |
Publisher: | Oxford University Press (OUP) |
Issue Date: | 2012 |
ISSN: | 0027-8874 1460-2105 |
Statement of Responsibility: | Aung Ko Win, Noralane M. Lindor, Joanne P. Young, Finlay A. Macrae, Graeme P. Young, Elizabeth Williamson, Susan Parry, Jack Goldblatt, Lara Lipton, Ingrid Winship, Barbara Leggett, Katherine M. Tucker, Graham G. Giles, Daniel D. Buchanan, Mark Clendenning, Christophe Rosty, Julie Arnold, A. Joan Levine, Robert W. Haile, Steven Gallinger, Loïc Le Marchand, Polly A. Newcomb, John L. Hopper and Mark A. Jenkins |
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. |
Keywords: | Colorectal Neoplasms, Hereditary Nonpolyposis Urogenital Neoplasms Adaptor Proteins, Signal Transducing DNA-Binding Proteins Nuclear Proteins Confounding Factors (Epidemiology) Germ-Line Mutation Adenosine Triphosphatases MutS Homolog 2 Protein DNA Repair Enzymes Chromatography, High Pressure Liquid Kaplan-Meier Estimate DNA Mismatch Repair Digestive System Neoplasms |
Rights: | © The Author 2012. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. |
DOI: | 10.1093/jnci/djs351 |
Published version: | http://dx.doi.org/10.1093/jnci/djs351 |
Appears in Collections: | Aurora harvest 2 Medicine publications |
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