Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome

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 GallingerLoïc Le Marchand, Polly A. Newcomb, John L. Hopper, Mark A. Jenkins

Research output: Contribution to journalArticlepeer-review

137 Scopus citations

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.MethodsWe 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 KaplanMeier 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 periodspecific standardized incidence ratios (SIRs) of cancers following colorectal cancer, compared with the general population.ResultsFollowing 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).ConclusionCarriers 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.

Original languageEnglish (US)
Pages (from-to)1363-1372
Number of pages10
JournalJournal of the National Cancer Institute
Volume104
Issue number18
DOIs
StatePublished - Sep 19 2012

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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