Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: A prospective cohort study

Aung Ko Win, Joanne P. Young, Noralane Morey Lindor, Katherine M. Tucker, Dennis J. Ahnen, Graeme P. Young, Daniel D. Buchanan, Mark Clendenning, Graham G. Giles, Ingrid Winship, Finlay A. Macrae, Jack Goldblatt, Melissa C. Southey, Julie Arnold, Stephen N Thibodeau, Shanaka R. Gunawardena, Bharati Bapat, John A. Baron, Graham Casey, Steven GallingerLoïc Le Marchand, Polly A. Newcomb, Robert W. Haile, John L. Hopper, Mark A. Jenkins

Research output: Contribution to journalArticle

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Abstract

Purpose: To determine whether cancer risks for carriers and noncarriers from families with a mismatch repair (MMR) gene mutation are increased above the risks of the general population. Patients and Methods: We prospectively followed a cohort of 446 unaffected carriers of an MMR gene mutation (MLH1, n = 161; MSH2, n = 222; MSH6, n = 47; and PMS2, n = 16) and 1,029 their unaffected relatives who did not carry a mutation every 5 years at recruitment centers of the Colon Cancer Family Registry. For comparison of cancer risk with the general population, we estimated country-, age-, and sex-specific standardized incidence ratios (SIRs) of cancer for carriers and noncarriers. Results: Over a median follow-up of 5 years, mutation carriers had an increased risk of colorectal cancer (CRC; SIR, 20.48; 95% CI, 11.71 to 33.27; P < .001), endometrial cancer (SIR, 30.62; 95% CI, 11.24 to 66.64; P < .001), ovarian cancer (SIR, 18.81; 95% CI, 3.88 to 54.95; P < .001), renal cancer (SIR, 11.22; 95% CI, 2.31 to 32.79; P < .001), pancreatic cancer (SIR, 10.68; 95% CI, 2.68 to 47.70; P = .001), gastric cancer (SIR, 9.78; 95% CI, 1.18 to 35.30; P = .009), urinary bladder cancer (SIR, 9.51; 95% CI, 1.15 to 34.37; P = .009), and female breast cancer (SIR, 3.95; 95% CI, 1.59 to 8.13; P = .001). We found no evidence of their noncarrier relatives having an increased risk of any cancer, including CRC (SIR, 1.02; 95% CI, 0.33 to 2.39; P = .97). Conclusion: We confirmed that carriers of an MMR gene mutation were at increased risk of a wide variety of cancers, including some cancers not previously recognized as being a result of MMR mutations, and found no evidence of an increased risk of cancer for their noncarrier relatives.

Original languageEnglish (US)
Pages (from-to)958-964
Number of pages7
JournalJournal of Clinical Oncology
Volume30
Issue number9
DOIs
StatePublished - Mar 20 2012

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DNA Mismatch Repair
Colorectal Neoplasms
Cohort Studies
Prospective Studies
Mutation
Incidence
Genes
Neoplasms
Kidney Neoplasms
Endometrial Neoplasms
Pancreatic Neoplasms
Urinary Bladder Neoplasms
Ovarian Neoplasms
Colonic Neoplasms
Population
Stomach Neoplasms
Registries
Breast Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation : A prospective cohort study. / Win, Aung Ko; Young, Joanne P.; Lindor, Noralane Morey; Tucker, Katherine M.; Ahnen, Dennis J.; Young, Graeme P.; Buchanan, Daniel D.; Clendenning, Mark; Giles, Graham G.; Winship, Ingrid; Macrae, Finlay A.; Goldblatt, Jack; Southey, Melissa C.; Arnold, Julie; Thibodeau, Stephen N; Gunawardena, Shanaka R.; Bapat, Bharati; Baron, John A.; Casey, Graham; Gallinger, Steven; Le Marchand, Loïc; Newcomb, Polly A.; Haile, Robert W.; Hopper, John L.; Jenkins, Mark A.

In: Journal of Clinical Oncology, Vol. 30, No. 9, 20.03.2012, p. 958-964.

Research output: Contribution to journalArticle

Win, AK, Young, JP, Lindor, NM, Tucker, KM, Ahnen, DJ, Young, GP, Buchanan, DD, Clendenning, M, Giles, GG, Winship, I, Macrae, FA, Goldblatt, J, Southey, MC, Arnold, J, Thibodeau, SN, Gunawardena, SR, Bapat, B, Baron, JA, Casey, G, Gallinger, S, Le Marchand, L, Newcomb, PA, Haile, RW, Hopper, JL & Jenkins, MA 2012, 'Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: A prospective cohort study', Journal of Clinical Oncology, vol. 30, no. 9, pp. 958-964. https://doi.org/10.1200/JCO.2011.39.5590
Win, Aung Ko ; Young, Joanne P. ; Lindor, Noralane Morey ; Tucker, Katherine M. ; Ahnen, Dennis J. ; Young, Graeme P. ; Buchanan, Daniel D. ; Clendenning, Mark ; Giles, Graham G. ; Winship, Ingrid ; Macrae, Finlay A. ; Goldblatt, Jack ; Southey, Melissa C. ; Arnold, Julie ; Thibodeau, Stephen N ; Gunawardena, Shanaka R. ; Bapat, Bharati ; Baron, John A. ; Casey, Graham ; Gallinger, Steven ; Le Marchand, Loïc ; Newcomb, Polly A. ; Haile, Robert W. ; Hopper, John L. ; Jenkins, Mark A. / Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation : A prospective cohort study. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 9. pp. 958-964.
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abstract = "Purpose: To determine whether cancer risks for carriers and noncarriers from families with a mismatch repair (MMR) gene mutation are increased above the risks of the general population. Patients and Methods: We prospectively followed a cohort of 446 unaffected carriers of an MMR gene mutation (MLH1, n = 161; MSH2, n = 222; MSH6, n = 47; and PMS2, n = 16) and 1,029 their unaffected relatives who did not carry a mutation every 5 years at recruitment centers of the Colon Cancer Family Registry. For comparison of cancer risk with the general population, we estimated country-, age-, and sex-specific standardized incidence ratios (SIRs) of cancer for carriers and noncarriers. Results: Over a median follow-up of 5 years, mutation carriers had an increased risk of colorectal cancer (CRC; SIR, 20.48; 95{\%} CI, 11.71 to 33.27; P < .001), endometrial cancer (SIR, 30.62; 95{\%} CI, 11.24 to 66.64; P < .001), ovarian cancer (SIR, 18.81; 95{\%} CI, 3.88 to 54.95; P < .001), renal cancer (SIR, 11.22; 95{\%} CI, 2.31 to 32.79; P < .001), pancreatic cancer (SIR, 10.68; 95{\%} CI, 2.68 to 47.70; P = .001), gastric cancer (SIR, 9.78; 95{\%} CI, 1.18 to 35.30; P = .009), urinary bladder cancer (SIR, 9.51; 95{\%} CI, 1.15 to 34.37; P = .009), and female breast cancer (SIR, 3.95; 95{\%} CI, 1.59 to 8.13; P = .001). We found no evidence of their noncarrier relatives having an increased risk of any cancer, including CRC (SIR, 1.02; 95{\%} CI, 0.33 to 2.39; P = .97). Conclusion: We confirmed that carriers of an MMR gene mutation were at increased risk of a wide variety of cancers, including some cancers not previously recognized as being a result of MMR mutations, and found no evidence of an increased risk of cancer for their noncarrier relatives.",
author = "Win, {Aung Ko} and Young, {Joanne P.} and Lindor, {Noralane Morey} and Tucker, {Katherine M.} and Ahnen, {Dennis J.} and Young, {Graeme P.} and Buchanan, {Daniel D.} and Mark Clendenning and Giles, {Graham G.} and Ingrid Winship and Macrae, {Finlay A.} and Jack Goldblatt and Southey, {Melissa C.} and Julie Arnold and Thibodeau, {Stephen N} and Gunawardena, {Shanaka R.} and Bharati Bapat and Baron, {John A.} and Graham Casey and Steven Gallinger and {Le Marchand}, Lo{\"i}c and Newcomb, {Polly A.} and Haile, {Robert W.} and Hopper, {John L.} and Jenkins, {Mark A.}",
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TY - JOUR

T1 - Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation

T2 - A prospective cohort study

AU - Win, Aung Ko

AU - Young, Joanne P.

AU - Lindor, Noralane Morey

AU - Tucker, Katherine M.

AU - Ahnen, Dennis J.

AU - Young, Graeme P.

AU - Buchanan, Daniel D.

AU - Clendenning, Mark

AU - Giles, Graham G.

AU - Winship, Ingrid

AU - Macrae, Finlay A.

AU - Goldblatt, Jack

AU - Southey, Melissa C.

AU - Arnold, Julie

AU - Thibodeau, Stephen N

AU - Gunawardena, Shanaka R.

AU - Bapat, Bharati

AU - Baron, John A.

AU - Casey, Graham

AU - Gallinger, Steven

AU - Le Marchand, Loïc

AU - Newcomb, Polly A.

AU - Haile, Robert W.

AU - Hopper, John L.

AU - Jenkins, Mark A.

PY - 2012/3/20

Y1 - 2012/3/20

N2 - Purpose: To determine whether cancer risks for carriers and noncarriers from families with a mismatch repair (MMR) gene mutation are increased above the risks of the general population. Patients and Methods: We prospectively followed a cohort of 446 unaffected carriers of an MMR gene mutation (MLH1, n = 161; MSH2, n = 222; MSH6, n = 47; and PMS2, n = 16) and 1,029 their unaffected relatives who did not carry a mutation every 5 years at recruitment centers of the Colon Cancer Family Registry. For comparison of cancer risk with the general population, we estimated country-, age-, and sex-specific standardized incidence ratios (SIRs) of cancer for carriers and noncarriers. Results: Over a median follow-up of 5 years, mutation carriers had an increased risk of colorectal cancer (CRC; SIR, 20.48; 95% CI, 11.71 to 33.27; P < .001), endometrial cancer (SIR, 30.62; 95% CI, 11.24 to 66.64; P < .001), ovarian cancer (SIR, 18.81; 95% CI, 3.88 to 54.95; P < .001), renal cancer (SIR, 11.22; 95% CI, 2.31 to 32.79; P < .001), pancreatic cancer (SIR, 10.68; 95% CI, 2.68 to 47.70; P = .001), gastric cancer (SIR, 9.78; 95% CI, 1.18 to 35.30; P = .009), urinary bladder cancer (SIR, 9.51; 95% CI, 1.15 to 34.37; P = .009), and female breast cancer (SIR, 3.95; 95% CI, 1.59 to 8.13; P = .001). We found no evidence of their noncarrier relatives having an increased risk of any cancer, including CRC (SIR, 1.02; 95% CI, 0.33 to 2.39; P = .97). Conclusion: We confirmed that carriers of an MMR gene mutation were at increased risk of a wide variety of cancers, including some cancers not previously recognized as being a result of MMR mutations, and found no evidence of an increased risk of cancer for their noncarrier relatives.

AB - Purpose: To determine whether cancer risks for carriers and noncarriers from families with a mismatch repair (MMR) gene mutation are increased above the risks of the general population. Patients and Methods: We prospectively followed a cohort of 446 unaffected carriers of an MMR gene mutation (MLH1, n = 161; MSH2, n = 222; MSH6, n = 47; and PMS2, n = 16) and 1,029 their unaffected relatives who did not carry a mutation every 5 years at recruitment centers of the Colon Cancer Family Registry. For comparison of cancer risk with the general population, we estimated country-, age-, and sex-specific standardized incidence ratios (SIRs) of cancer for carriers and noncarriers. Results: Over a median follow-up of 5 years, mutation carriers had an increased risk of colorectal cancer (CRC; SIR, 20.48; 95% CI, 11.71 to 33.27; P < .001), endometrial cancer (SIR, 30.62; 95% CI, 11.24 to 66.64; P < .001), ovarian cancer (SIR, 18.81; 95% CI, 3.88 to 54.95; P < .001), renal cancer (SIR, 11.22; 95% CI, 2.31 to 32.79; P < .001), pancreatic cancer (SIR, 10.68; 95% CI, 2.68 to 47.70; P = .001), gastric cancer (SIR, 9.78; 95% CI, 1.18 to 35.30; P = .009), urinary bladder cancer (SIR, 9.51; 95% CI, 1.15 to 34.37; P = .009), and female breast cancer (SIR, 3.95; 95% CI, 1.59 to 8.13; P = .001). We found no evidence of their noncarrier relatives having an increased risk of any cancer, including CRC (SIR, 1.02; 95% CI, 0.33 to 2.39; P = .97). Conclusion: We confirmed that carriers of an MMR gene mutation were at increased risk of a wide variety of cancers, including some cancers not previously recognized as being a result of MMR mutations, and found no evidence of an increased risk of cancer for their noncarrier relatives.

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