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, Loic, Casey, Graham, Haile, Robert W., Newcomb, Polly A., Thibodeau, Stephen N., Hopper, John L., Gallinger, Steven, Winship, Ingrid M., Lindor, Noralane M. and Jenkins, Mark A. (2016) Risk of extracolonic cancers for people with biallelic and monoallelic mutations in MUTYH. International Journal of Cancer, 139 7: 1557-1563. doi:10.1002/ijc.30197


Author 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, Loic
Casey, Graham
Haile, Robert W.
Newcomb, Polly A.
Thibodeau, Stephen N.
Hopper, John L.
Gallinger, Steven
Winship, Ingrid M.
Lindor, Noralane M.
Jenkins, Mark A.
Title Risk of extracolonic cancers for people with biallelic and monoallelic mutations in MUTYH
Formatted title
Risk of extracolonic cancers for people with biallelic and monoallelic mutations in MUTYH
Journal name International Journal of Cancer   Check publisher's open access policy
ISSN 1097-0215
0020-7136
Publication date 2016-10-01
Year available 2016
Sub-type Article (original research)
DOI 10.1002/ijc.30197
Open Access Status Not yet assessed
Volume 139
Issue 7
Start page 1557
End page 1563
Total pages 7
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Language eng
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.
Formatted 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.
Keyword Cancer risk
MUTYH
MUTYH-associated polyposis
Penetrance
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID HHSN261201000035C
HHSN261201000140C
U01 CA074799
U24 CA074783
N01 CN067009
U24 CA074794
N01PC35137
U24 CA074806
HHSN261201300009C
U24 CA097735
U01 CA074794
HHSN261201300012I
N01PC35142
HHSN261201000035I
HHSN261201000034C
U01 CA097735
UM1 CA167551
U58 DP003862
U01 CA074783
U24 CA074799
U01 CA074806
U24 CA074800
U01 CA074800
Institutional Status UQ

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Sub-type: Article (original research)
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