ArticleCancer prevention research (Philadelphia, Pa.)2022
Incident Cancer Risk and Signatures Among Older MUTYH Carriers: Analysis of Population-Based and Genomic Cohorts.
Article in Cancer prevention research (Philadelphia, Pa.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed, 1 citations in OpenAlex.
- Germline haploinsufficiency of MUTYH causes mutational signature SBS18 in multiple tumour types and specifically raises colorectal cancer risk.NPJ precision oncology · 2026Article
- Lynch syndrome: influence of additional susceptibility variants on cancer risk.European journal of human genetics : EJHG · 2023Article
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Authors and funding
16 authors at 9 institutions in 4 countries.
Funding
Abstract
MUTYH 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. MUTYH 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 MUTYH carriers demonstrated an increased risk for overall cancer incidence [multivariable HR, 1.66; 95% confidence interval (CI), 1.03-2.68; P = 0.038] driven by increased colorectal cancer incidence (multivariable HR, 3.55; 95% CI, 1.42-8.78; P = 0.007), as opposed to extracolonic cancer incidence (multivariable HR, 1.40; 95% CI, 0.81-2.44; P = 0.229). Female carriers did not demonstrate increased risk of cancer, colorectal cancer, or extracolonic cancers. Analysis of mutation signatures from cancers of MUTYH 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 diverse mechanisms of carcinogenesis in carriers compared with those who inherit biallelic MUTYH mutations. PREVENTION RELEVANCE: Despite absence of loss of heterozygosity in colorectal cancers, elderly male MUTYH carriers appeared to be at increased of colorectal cancer.
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