Cancer risks for monoallelic MUTYH mutation carriers with a family history of colorectal cancer

Aung Ko Win, Sean P. Cleary, James G. Dowty, John A. Baron, Joanne P. Young, Daniel D. Buchanan, Melissa C. Southey, Terrilea Burnett, Patrick S. Parfrey, Roger C. Green, Loïc Le Marchand, Polly A. Newcomb, Robert W. Haile, Noralane Morey Lindor, John L. Hopper, Steven Gallinger, Mark A. Jenkins

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Cancer risks for a person who has inherited a MUTYH mutation from only one parent (monoallelic mutation carrier) are uncertain. Using the Colon Cancer Family Registry and Newfoundland Familial Colon Cancer Registry, we identified 2,179 first- and second-degree relatives of 144 incident colorectal cancer (CRC) cases who were monoallelic or biallelic mutation carriers ascertained by sampling population complete cancer registries in the United States, Canada and Australia. Using Cox regression weighted to adjust for sampling on family history, we estimated that the country-, age- and sex-specific standardized incidence ratios (SIRs) for monoallelic mutation carriers, compared to the general population, were: 2.04 (95% confidence interval, CI 1.56-2.70; p < 0.001) for CRC, 3.24 (95%CI 2.18-4.98; p < 0.001) for gastric cancer, 3.09 (95%CI 1.07-12.25; p = 0.07) for liver cancer and 2.33 (95%CI 1.18-5.08; p = 0.02) for endometrial cancer. Age-specific cumulative risks to age 70 years, estimated using the SIRs and US population incidences, were: for CRC, 6% (95%CI 5-8%) for men and 4% (95%CI 3-6%) for women; for gastric cancer, 2% (95%CI 1-3%) for men and 0.7% (95%CI 0.5-1%) for women; for liver cancer, 1% (95%CI 0.3-3%) for men and 0.3% (95%CI 0.1-1%) for women and for endometrial cancer, 4% (95%CI 2-8%). There was no evidence of increased risks for cancers of the brain, pancreas, kidney, lung, breast or prostate. Monoallelic MUTYH mutation carriers with a family history of CRC, such as those identified from screening multiple-case CRC families, are at increased risk of colorectal, gastric, endometrial and possibly liver cancers.

Original languageEnglish (US)
Pages (from-to)2256-2262
Number of pages7
JournalInternational Journal of Cancer
Volume129
Issue number9
DOIs
StatePublished - Nov 1 2011

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Colorectal Neoplasms
Liver Neoplasms
Mutation
Registries
Neoplasms
Endometrial Neoplasms
Colonic Neoplasms
Stomach Neoplasms
Incidence
Population
Newfoundland and Labrador
Pancreatic Neoplasms
Brain Neoplasms
Canada
Prostate
Stomach
Breast
Confidence Intervals
Kidney
Lung

Keywords

  • colorectal cancer
  • extracolonic cancer
  • monoallelic MUTYH mutations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Win, A. K., Cleary, S. P., Dowty, J. G., Baron, J. A., Young, J. P., Buchanan, D. D., ... Jenkins, M. A. (2011). Cancer risks for monoallelic MUTYH mutation carriers with a family history of colorectal cancer. International Journal of Cancer, 129(9), 2256-2262. https://doi.org/10.1002/ijc.25870

Cancer risks for monoallelic MUTYH mutation carriers with a family history of colorectal cancer. / Win, Aung Ko; Cleary, Sean P.; Dowty, James G.; Baron, John A.; Young, Joanne P.; Buchanan, Daniel D.; Southey, Melissa C.; Burnett, Terrilea; Parfrey, Patrick S.; Green, Roger C.; Marchand, Loïc Le; Newcomb, Polly A.; Haile, Robert W.; Lindor, Noralane Morey; Hopper, John L.; Gallinger, Steven; Jenkins, Mark A.

In: International Journal of Cancer, Vol. 129, No. 9, 01.11.2011, p. 2256-2262.

Research output: Contribution to journalArticle

Win, AK, Cleary, SP, Dowty, JG, Baron, JA, Young, JP, Buchanan, DD, Southey, MC, Burnett, T, Parfrey, PS, Green, RC, Marchand, LL, Newcomb, PA, Haile, RW, Lindor, NM, Hopper, JL, Gallinger, S & Jenkins, MA 2011, 'Cancer risks for monoallelic MUTYH mutation carriers with a family history of colorectal cancer', International Journal of Cancer, vol. 129, no. 9, pp. 2256-2262. https://doi.org/10.1002/ijc.25870
Win, Aung Ko ; Cleary, Sean P. ; Dowty, James G. ; Baron, John A. ; Young, Joanne P. ; Buchanan, Daniel D. ; Southey, Melissa C. ; Burnett, Terrilea ; Parfrey, Patrick S. ; Green, Roger C. ; Marchand, Loïc Le ; Newcomb, Polly A. ; Haile, Robert W. ; Lindor, Noralane Morey ; Hopper, John L. ; Gallinger, Steven ; Jenkins, Mark A. / Cancer risks for monoallelic MUTYH mutation carriers with a family history of colorectal cancer. In: International Journal of Cancer. 2011 ; Vol. 129, No. 9. pp. 2256-2262.
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N2 - Cancer risks for a person who has inherited a MUTYH mutation from only one parent (monoallelic mutation carrier) are uncertain. Using the Colon Cancer Family Registry and Newfoundland Familial Colon Cancer Registry, we identified 2,179 first- and second-degree relatives of 144 incident colorectal cancer (CRC) cases who were monoallelic or biallelic mutation carriers ascertained by sampling population complete cancer registries in the United States, Canada and Australia. Using Cox regression weighted to adjust for sampling on family history, we estimated that the country-, age- and sex-specific standardized incidence ratios (SIRs) for monoallelic mutation carriers, compared to the general population, were: 2.04 (95% confidence interval, CI 1.56-2.70; p < 0.001) for CRC, 3.24 (95%CI 2.18-4.98; p < 0.001) for gastric cancer, 3.09 (95%CI 1.07-12.25; p = 0.07) for liver cancer and 2.33 (95%CI 1.18-5.08; p = 0.02) for endometrial cancer. Age-specific cumulative risks to age 70 years, estimated using the SIRs and US population incidences, were: for CRC, 6% (95%CI 5-8%) for men and 4% (95%CI 3-6%) for women; for gastric cancer, 2% (95%CI 1-3%) for men and 0.7% (95%CI 0.5-1%) for women; for liver cancer, 1% (95%CI 0.3-3%) for men and 0.3% (95%CI 0.1-1%) for women and for endometrial cancer, 4% (95%CI 2-8%). There was no evidence of increased risks for cancers of the brain, pancreas, kidney, lung, breast or prostate. Monoallelic MUTYH mutation carriers with a family history of CRC, such as those identified from screening multiple-case CRC families, are at increased risk of colorectal, gastric, endometrial and possibly liver cancers.

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