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Cancer risks for monoallelic MUTYH mutation carriers with a family history of colorectal cancer
Author(s) -
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 M.,
Hopper John L.,
Gallinger Steven,
Jenkins Mark A.
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25870
Subject(s) - medicine , cancer , colorectal cancer , mutyh , endometrial cancer , population , family history , cancer registry , lynch syndrome , oncology , gynecology , mutation , germline mutation , genetics , biology , dna mismatch repair , environmental health , gene
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.