ORCID Profile
0000-0002-5424-4401
Current Organisation
Massachusetts General Hospital
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Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1940-6207.C.6547022
Abstract: Abstract i MUTYH /i carriers have an increased colorectal cancer risk in case–control studies, with loss of heterozygosity (LOH) as the presumed mechanism. We evaluated cancer risk among carriers in a prospective, population-based cohort of older adults. In addition, we assessed if cancers from carriers demonstrated mutational signatures (G:C T:A transversions) associated with early LOH. We calculated incident risk of cancer and colorectal cancer among 13,131 sequenced study participants of the ASPirin in Reducing Events in the Elderly cohort, stratified by sex and adjusting for age, smoking, alcohol use, BMI, polyp history, history of cancer, and aspirin use. i MUTYH /i carriers were identified among 13,033 participants in The Cancer Genome Atlas and International Cancer Genome Consortium, and somatic signatures of cancers were analyzed. Male i MUTYH /i carriers demonstrated an increased risk for overall cancer incidence [multivariable HR, 1.66 95% confidence interval (CI), 1.03–2.68 i P /i = 0.038] driven by increased colorectal cancer incidence (multivariable HR, 3.55 95% CI, 1.42–8.78 i P /i = 0.007), as opposed to extracolonic cancer incidence (multivariable HR, 1.40 95% CI, 0.81–2.44 i P /i = 0.229). Female carriers did not demonstrate increased risk of cancer, colorectal cancer, or extracolonic cancers. Analysis of mutation signatures from cancers of i MUTYH /i carriers revealed no significant contribution toward early mutagenesis from widespread G:C T:A transversions among gastrointestinal epithelial cancers. Among cancers from carriers, somatic transversions associated with base-excision repair deficiency are uncommon, suggestive of erse mechanisms of carcinogenesis in carriers compared with those who inherit biallelic i MUTYH /i mutations. Prevention Relevance: Despite absence of loss of heterozygosity in colorectal cancers, elderly male i MUTYH /i carriers appeared to be at increased of colorectal cancer. /
Publisher: Springer Science and Business Media LLC
Date: 24-07-2013
DOI: 10.1038/LEU.2013.223
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1940-6207.22533314
Abstract: Supplementary Figure from Incident Cancer Risk and Signatures Among Older i MUTYH /i Carriers: Analysis of Population-Based and Genomic Cohorts
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1940-6207.22533314.V1
Abstract: Supplementary Figure from Incident Cancer Risk and Signatures Among Older i MUTYH /i Carriers: Analysis of Population-Based and Genomic Cohorts
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1940-6207.C.6547022.V1
Abstract: Abstract i MUTYH /i carriers have an increased colorectal cancer risk in case–control studies, with loss of heterozygosity (LOH) as the presumed mechanism. We evaluated cancer risk among carriers in a prospective, population-based cohort of older adults. In addition, we assessed if cancers from carriers demonstrated mutational signatures (G:C T:A transversions) associated with early LOH. We calculated incident risk of cancer and colorectal cancer among 13,131 sequenced study participants of the ASPirin in Reducing Events in the Elderly cohort, stratified by sex and adjusting for age, smoking, alcohol use, BMI, polyp history, history of cancer, and aspirin use. i MUTYH /i carriers were identified among 13,033 participants in The Cancer Genome Atlas and International Cancer Genome Consortium, and somatic signatures of cancers were analyzed. Male i MUTYH /i carriers demonstrated an increased risk for overall cancer incidence [multivariable HR, 1.66 95% confidence interval (CI), 1.03–2.68 i P /i = 0.038] driven by increased colorectal cancer incidence (multivariable HR, 3.55 95% CI, 1.42–8.78 i P /i = 0.007), as opposed to extracolonic cancer incidence (multivariable HR, 1.40 95% CI, 0.81–2.44 i P /i = 0.229). Female carriers did not demonstrate increased risk of cancer, colorectal cancer, or extracolonic cancers. Analysis of mutation signatures from cancers of i MUTYH /i carriers revealed no significant contribution toward early mutagenesis from widespread G:C T:A transversions among gastrointestinal epithelial cancers. Among cancers from carriers, somatic transversions associated with base-excision repair deficiency are uncommon, suggestive of erse mechanisms of carcinogenesis in carriers compared with those who inherit biallelic i MUTYH /i mutations. Prevention Relevance: Despite absence of loss of heterozygosity in colorectal cancers, elderly male i MUTYH /i carriers appeared to be at increased of colorectal cancer. /
Publisher: American Association for Cancer Research (AACR)
Date: 24-05-2022
DOI: 10.1158/1940-6207.CAPR-22-0080
Abstract: Despite absence of loss of heterozygosity in colorectal cancers, elderly male MUTYH carriers appeared to be at increased of colorectal cancer.
Location: United States of America
No related grants have been discovered for Jonathan Downie.