Risk of extracolonic cancers for people with biallelic and monoallelic mutations in MUTYH

Aung Ko Win, Jeanette C. Reece, James G. Dowty, Daniel D. Buchanan, Mark Clendenning, Christophe Rosty, Melissa C. Southey, Joanne P. Young, Sean P. Cleary, Hyeja Kim, Michelle Cotterchio, Finlay A. Macrae, Katherine M. Tucker, John A. Baron, Terrilea Burnett, Loïc Le Marchand, Graham Casey, Robert W. Haile, Polly A. Newcomb, Stephen N ThibodeauJohn L. Hopper, Steven Gallinger, Ingrid M. Winship, Noralane Morey Lindor, Mark A. Jenkins

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Germline mutations in the DNA base excision repair gene MUTYH are known to increase a carrier's risk of colorectal cancer. However, the risks of other (extracolonic) cancers for MUTYH mutation carriers are not well defined. We identified 266 probands (91% Caucasians) with a MUTYH mutation (41 biallelic and 225 monoallelic) from the Colon Cancer Family Registry. Mutation status, sex, age and histories of cancer from their 1,903 first- and 3,255 second-degree relatives were analyzed using modified segregation analysis conditioned on the ascertainment criteria. Compared with incidences for the general population, hazard ratios (HRs) (95% confidence intervals [CIs]) for biallelic MUTYH mutation carriers were: urinary bladder cancer 19 (3.7–97) and ovarian cancer 17 (2.4–115). The HRs (95% CI) for monoallelic MUTYH mutation carriers were: gastric cancer 9.3 (6.7–13); hepatobiliary cancer 4.5 (2.7–7.5); endometrial cancer 2.1 (1.1–3.9) and breast cancer 1.4 (1.0–2.0). There was no evidence for an increased risk of cancers at the other sites examined (brain, pancreas, kidney or prostate). Based on the USA population incidences, the estimated cumulative risks (95% CI) to age 70 years for biallelic mutation carriers were: bladder cancer 25% (5–77%) for males and 8% (2–33%) for females and ovarian cancer 14% (2–65%). The cumulative risks (95% CI) for monoallelic mutation carriers were: gastric cancer 5% (4–7%) for males and 2.3% (1.7–3.3%) for females; hepatobiliary cancer 3% (2–5%) for males and 1.4% (0.8–2.3%) for females; endometrial cancer 3% (2%–6%) and breast cancer 11% (8–16%). These unbiased estimates of both relative and absolute risks of extracolonic cancers for people, mostly Caucasians, with MUTYH mutations will be important for their clinical management.

Original languageEnglish (US)
Pages (from-to)1557-1563
Number of pages7
JournalInternational Journal of Cancer
Volume139
Issue number7
DOIs
StatePublished - Oct 1 2016

Fingerprint

Mutation
Neoplasms
Confidence Intervals
Endometrial Neoplasms
Urinary Bladder Neoplasms
Ovarian Neoplasms
Stomach Neoplasms
Breast Neoplasms
Germ-Line Mutation
Incidence
DNA Repair
Colonic Neoplasms
Population
Registries
Prostate
Pancreas
Colorectal Neoplasms
Kidney
DNA
Brain

Keywords

  • cancer risk
  • MUTYH
  • MUTYH-associated polyposis
  • penetrance

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Win, A. K., Reece, J. C., Dowty, J. G., Buchanan, D. D., Clendenning, M., Rosty, C., ... Jenkins, M. A. (2016). Risk of extracolonic cancers for people with biallelic and monoallelic mutations in MUTYH. International Journal of Cancer, 139(7), 1557-1563. https://doi.org/10.1002/ijc.30197

Risk of extracolonic cancers for people with biallelic and monoallelic mutations in MUTYH. / Win, Aung Ko; Reece, Jeanette C.; Dowty, James G.; Buchanan, Daniel D.; Clendenning, Mark; Rosty, Christophe; Southey, Melissa C.; Young, Joanne P.; Cleary, Sean P.; Kim, Hyeja; Cotterchio, Michelle; Macrae, Finlay A.; Tucker, Katherine M.; Baron, John A.; Burnett, Terrilea; Le Marchand, Loïc; Casey, Graham; Haile, Robert W.; Newcomb, Polly A.; Thibodeau, Stephen N; Hopper, John L.; Gallinger, Steven; Winship, Ingrid M.; Lindor, Noralane Morey; Jenkins, Mark A.

In: International Journal of Cancer, Vol. 139, No. 7, 01.10.2016, p. 1557-1563.

Research output: Contribution to journalArticle

Win, AK, Reece, JC, Dowty, JG, Buchanan, DD, Clendenning, M, Rosty, C, Southey, MC, Young, JP, Cleary, SP, Kim, H, Cotterchio, M, Macrae, FA, Tucker, KM, Baron, JA, Burnett, T, Le Marchand, L, Casey, G, Haile, RW, Newcomb, PA, Thibodeau, SN, Hopper, JL, Gallinger, S, Winship, IM, Lindor, NM & Jenkins, MA 2016, 'Risk of extracolonic cancers for people with biallelic and monoallelic mutations in MUTYH', International Journal of Cancer, vol. 139, no. 7, pp. 1557-1563. https://doi.org/10.1002/ijc.30197
Win AK, Reece JC, Dowty JG, Buchanan DD, Clendenning M, Rosty C et al. Risk of extracolonic cancers for people with biallelic and monoallelic mutations in MUTYH. International Journal of Cancer. 2016 Oct 1;139(7):1557-1563. https://doi.org/10.1002/ijc.30197
Win, Aung Ko ; Reece, Jeanette C. ; Dowty, James G. ; Buchanan, Daniel D. ; Clendenning, Mark ; Rosty, Christophe ; Southey, Melissa C. ; Young, Joanne P. ; Cleary, Sean P. ; Kim, Hyeja ; Cotterchio, Michelle ; Macrae, Finlay A. ; Tucker, Katherine M. ; Baron, John A. ; Burnett, Terrilea ; Le Marchand, Loïc ; Casey, Graham ; Haile, Robert W. ; Newcomb, Polly A. ; Thibodeau, Stephen N ; Hopper, John L. ; Gallinger, Steven ; Winship, Ingrid M. ; Lindor, Noralane Morey ; Jenkins, Mark A. / Risk of extracolonic cancers for people with biallelic and monoallelic mutations in MUTYH. In: International Journal of Cancer. 2016 ; Vol. 139, No. 7. pp. 1557-1563.
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abstract = "Germline mutations in the DNA base excision repair gene MUTYH are known to increase a carrier's risk of colorectal cancer. However, the risks of other (extracolonic) cancers for MUTYH mutation carriers are not well defined. We identified 266 probands (91{\%} Caucasians) with a MUTYH mutation (41 biallelic and 225 monoallelic) from the Colon Cancer Family Registry. Mutation status, sex, age and histories of cancer from their 1,903 first- and 3,255 second-degree relatives were analyzed using modified segregation analysis conditioned on the ascertainment criteria. Compared with incidences for the general population, hazard ratios (HRs) (95{\%} confidence intervals [CIs]) for biallelic MUTYH mutation carriers were: urinary bladder cancer 19 (3.7–97) and ovarian cancer 17 (2.4–115). The HRs (95{\%} CI) for monoallelic MUTYH mutation carriers were: gastric cancer 9.3 (6.7–13); hepatobiliary cancer 4.5 (2.7–7.5); endometrial cancer 2.1 (1.1–3.9) and breast cancer 1.4 (1.0–2.0). There was no evidence for an increased risk of cancers at the other sites examined (brain, pancreas, kidney or prostate). Based on the USA population incidences, the estimated cumulative risks (95{\%} CI) to age 70 years for biallelic mutation carriers were: bladder cancer 25{\%} (5–77{\%}) for males and 8{\%} (2–33{\%}) for females and ovarian cancer 14{\%} (2–65{\%}). The cumulative risks (95{\%} CI) for monoallelic mutation carriers were: gastric cancer 5{\%} (4–7{\%}) for males and 2.3{\%} (1.7–3.3{\%}) for females; hepatobiliary cancer 3{\%} (2–5{\%}) for males and 1.4{\%} (0.8–2.3{\%}) for females; endometrial cancer 3{\%} (2{\%}–6{\%}) and breast cancer 11{\%} (8–16{\%}). These unbiased estimates of both relative and absolute risks of extracolonic cancers for people, mostly Caucasians, with MUTYH mutations will be important for their clinical management.",
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AU - Win, Aung Ko

AU - Reece, Jeanette C.

AU - Dowty, James G.

AU - Buchanan, Daniel D.

AU - Clendenning, Mark

AU - Rosty, Christophe

AU - Southey, Melissa C.

AU - Young, Joanne P.

AU - Cleary, Sean P.

AU - Kim, Hyeja

AU - Cotterchio, Michelle

AU - Macrae, Finlay A.

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AU - Casey, Graham

AU - Haile, Robert W.

AU - Newcomb, Polly A.

AU - Thibodeau, Stephen N

AU - Hopper, John L.

AU - Gallinger, Steven

AU - Winship, Ingrid M.

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AU - Jenkins, Mark A.

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N2 - Germline mutations in the DNA base excision repair gene MUTYH are known to increase a carrier's risk of colorectal cancer. However, the risks of other (extracolonic) cancers for MUTYH mutation carriers are not well defined. We identified 266 probands (91% Caucasians) with a MUTYH mutation (41 biallelic and 225 monoallelic) from the Colon Cancer Family Registry. Mutation status, sex, age and histories of cancer from their 1,903 first- and 3,255 second-degree relatives were analyzed using modified segregation analysis conditioned on the ascertainment criteria. Compared with incidences for the general population, hazard ratios (HRs) (95% confidence intervals [CIs]) for biallelic MUTYH mutation carriers were: urinary bladder cancer 19 (3.7–97) and ovarian cancer 17 (2.4–115). The HRs (95% CI) for monoallelic MUTYH mutation carriers were: gastric cancer 9.3 (6.7–13); hepatobiliary cancer 4.5 (2.7–7.5); endometrial cancer 2.1 (1.1–3.9) and breast cancer 1.4 (1.0–2.0). There was no evidence for an increased risk of cancers at the other sites examined (brain, pancreas, kidney or prostate). Based on the USA population incidences, the estimated cumulative risks (95% CI) to age 70 years for biallelic mutation carriers were: bladder cancer 25% (5–77%) for males and 8% (2–33%) for females and ovarian cancer 14% (2–65%). The cumulative risks (95% CI) for monoallelic mutation carriers were: gastric cancer 5% (4–7%) for males and 2.3% (1.7–3.3%) for females; hepatobiliary cancer 3% (2–5%) for males and 1.4% (0.8–2.3%) for females; endometrial cancer 3% (2%–6%) and breast cancer 11% (8–16%). These unbiased estimates of both relative and absolute risks of extracolonic cancers for people, mostly Caucasians, with MUTYH mutations will be important for their clinical management.

AB - Germline mutations in the DNA base excision repair gene MUTYH are known to increase a carrier's risk of colorectal cancer. However, the risks of other (extracolonic) cancers for MUTYH mutation carriers are not well defined. We identified 266 probands (91% Caucasians) with a MUTYH mutation (41 biallelic and 225 monoallelic) from the Colon Cancer Family Registry. Mutation status, sex, age and histories of cancer from their 1,903 first- and 3,255 second-degree relatives were analyzed using modified segregation analysis conditioned on the ascertainment criteria. Compared with incidences for the general population, hazard ratios (HRs) (95% confidence intervals [CIs]) for biallelic MUTYH mutation carriers were: urinary bladder cancer 19 (3.7–97) and ovarian cancer 17 (2.4–115). The HRs (95% CI) for monoallelic MUTYH mutation carriers were: gastric cancer 9.3 (6.7–13); hepatobiliary cancer 4.5 (2.7–7.5); endometrial cancer 2.1 (1.1–3.9) and breast cancer 1.4 (1.0–2.0). There was no evidence for an increased risk of cancers at the other sites examined (brain, pancreas, kidney or prostate). Based on the USA population incidences, the estimated cumulative risks (95% CI) to age 70 years for biallelic mutation carriers were: bladder cancer 25% (5–77%) for males and 8% (2–33%) for females and ovarian cancer 14% (2–65%). The cumulative risks (95% CI) for monoallelic mutation carriers were: gastric cancer 5% (4–7%) for males and 2.3% (1.7–3.3%) for females; hepatobiliary cancer 3% (2–5%) for males and 1.4% (0.8–2.3%) for females; endometrial cancer 3% (2%–6%) and breast cancer 11% (8–16%). These unbiased estimates of both relative and absolute risks of extracolonic cancers for people, mostly Caucasians, with MUTYH mutations will be important for their clinical management.

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