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.2015-08-142015-08-142012Journal of the National Cancer Institute, 2012; 104(18):1363-13720027-88741460-2105http://hdl.handle.net/2440/93554BACKGROUND: 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.en© The Author 2012. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.Colorectal Neoplasms, Hereditary NonpolyposisUrogenital NeoplasmsAdaptor Proteins, Signal TransducingDNA-Binding ProteinsNuclear ProteinsConfounding Factors (Epidemiology)Germ-Line MutationAdenosine TriphosphatasesMutS Homolog 2 ProteinDNA Repair EnzymesChromatography, High Pressure LiquidKaplan-Meier EstimateDNA Mismatch RepairDigestive System NeoplasmsJournal article003001202710.1093/jnci/djs3510003091325000072-s2.0-84866658167143940Young, J. [0000-0002-1514-1522]