Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome

Aung Ko Win, Noralane Morey 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 journalArticle

126 Citations (Scopus)

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

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Hereditary Nonpolyposis Colorectal Neoplasms
Colorectal Neoplasms
Confidence Intervals
Neoplasms
Incidence
Kidney Pelvis
DNA Mismatch Repair
Prostatic Neoplasms
Mutation
Ureter
Endometrium
Genes
Small Intestine
Ovary
Stomach
Urinary Bladder
Breast
Breast Neoplasms
Germ-Line Mutation
Kidney Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Win, A. K., Lindor, N. M., Young, J. P., MacRae, F. A., Young, G. P., Williamson, E., ... Jenkins, M. A. (2012). Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome. Journal of the National Cancer Institute, 104(18), 1363-1372. https://doi.org/10.1093/jnci/djs351

Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome. / Win, Aung Ko; Lindor, Noralane Morey; 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; Joan Levine, A.; Haile, Robert W.; Gallinger, Steven; Marchand, Loïc Le; Newcomb, Polly A.; Hopper, John L.; Jenkins, Mark A.

In: Journal of the National Cancer Institute, Vol. 104, No. 18, 19.09.2012, p. 1363-1372.

Research output: Contribution to journalArticle

Win, AK, Lindor, NM, Young, JP, MacRae, FA, Young, GP, Williamson, E, Parry, S, Goldblatt, J, Lipton, L, Winship, I, Leggett, B, Tucker, KM, Giles, GG, Buchanan, DD, Clendenning, M, Rosty, C, Arnold, J, Joan Levine, A, Haile, RW, Gallinger, S, Marchand, LL, Newcomb, PA, Hopper, JL & Jenkins, MA 2012, 'Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome', Journal of the National Cancer Institute, vol. 104, no. 18, pp. 1363-1372. https://doi.org/10.1093/jnci/djs351
Win, Aung Ko ; Lindor, Noralane Morey ; 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 ; Joan Levine, A. ; Haile, Robert W. ; Gallinger, Steven ; Marchand, Loïc Le ; Newcomb, Polly A. ; Hopper, John L. ; Jenkins, Mark A. / Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome. In: Journal of the National Cancer Institute. 2012 ; Vol. 104, No. 18. pp. 1363-1372.
@article{3c550b3d4f9e494b94e8302c0e5c46f8,
title = "Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome",
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.",
author = "Win, {Aung Ko} and Lindor, {Noralane Morey} and Young, {Joanne P.} and MacRae, {Finlay A.} and Young, {Graeme P.} and Elizabeth Williamson and Susan Parry and Jack Goldblatt and Lara Lipton and Ingrid Winship and Barbara Leggett and Tucker, {Katherine M.} and Giles, {Graham G.} and Buchanan, {Daniel D.} and Mark Clendenning and Christophe Rosty and Julie Arnold and {Joan Levine}, A. and Haile, {Robert W.} and Steven Gallinger and Marchand, {Lo{\"i}c Le} and Newcomb, {Polly A.} and Hopper, {John L.} and Jenkins, {Mark A.}",
year = "2012",
month = "9",
day = "19",
doi = "10.1093/jnci/djs351",
language = "English (US)",
volume = "104",
pages = "1363--1372",
journal = "Journal of the National Cancer Institute",
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TY - JOUR

T1 - Risks of primary extracolonic cancers following colorectal cancer in lynch syndrome

AU - Win, Aung Ko

AU - Lindor, Noralane Morey

AU - Young, Joanne P.

AU - MacRae, Finlay A.

AU - Young, Graeme P.

AU - Williamson, Elizabeth

AU - Parry, Susan

AU - Goldblatt, Jack

AU - Lipton, Lara

AU - Winship, Ingrid

AU - Leggett, Barbara

AU - Tucker, Katherine M.

AU - Giles, Graham G.

AU - Buchanan, Daniel D.

AU - Clendenning, Mark

AU - Rosty, Christophe

AU - Arnold, Julie

AU - Joan Levine, A.

AU - Haile, Robert W.

AU - Gallinger, Steven

AU - Marchand, Loïc Le

AU - Newcomb, Polly A.

AU - Hopper, John L.

AU - Jenkins, Mark A.

PY - 2012/9/19

Y1 - 2012/9/19

N2 - 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.

AB - 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.

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