Evidence map›Paper›PMID 35609203›Full record

ArticleCancer prevention research (Philadelphia, Pa.)2022

Incident Cancer Risk and Signatures Among Older MUTYH Carriers: Analysis of Population-Based and Genomic Cohorts.

Jonathan M Downie, Moeen Riaz, Jing Xie, Minyi Lee, Andrew T Chan, Peter Gibbs, Suzanne G Orchard, Suzanne E Mahady, Robert P Sebra, Anne M Murray and 6 more

Open access · bronzeAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.1field-weighted citation impact, top 62% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 1 citations in OpenAlex.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 9 institutions in 4 countries.

Jonathan M Downie *Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-5424-4401
Moeen Riaz *Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.ORCID 0000-0001-5858-3788
Jing XieDepartment of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.ORCID 0000-0001-6694-3587
Minyi LeeGastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Andrew T ChanGastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0001-7284-6767
Peter GibbsDivision of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.ORCID 0000-0003-1423-4484
Suzanne G OrchardDepartment of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.ORCID 0000-0003-0211-3183
Suzanne E MahadyDepartment of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.ORCID 0000-0002-6788-2250
Robert P SebraDepartment of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York.
Anne M MurrayBerman Center for Outcomes and Clinical Research, Hennepin Healthcare Research Institute, Hennepin Healthcare, Minneapolis, Minnesota.ORCID 0000-0002-2787-8433
Finlay MacraeDepartment of Genomic Medicine, Family Cancer Clinic, Department of Medicine, Department of Pathology, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
Eric SchadtDepartment of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York.ORCID 0000-0002-7892-8808
Robyn L WoodsDepartment of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
John J McNeilDepartment of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.ORCID 0000-0002-1049-5129
Paul LacazeDepartment of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
Manish GalaGastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-3126-0783
General Department of Preventive Medicine · VNCenter for Genomic Science · ITThe Royal Melbourne Hospital · AUBerman Center for Outcomes and Clinical Research · USBoston University · USBroad Institute · USHarvard University · USMassachusetts General Hospital · USThe University of Melbourne · AU

Funding

ASPirin in Reducing Events in the ElderlyU01AG029824 · NIA · HENNEPIN HEALTHCARE RESEARCH INSTITUTE · PI MCNEIL, JOHN JAMES, MURRAY, ANNE M · 2009 to 2018
$64.6M
Main Administrative CoreU19AG062682 · NIA · HENNEPIN HEALTHCARE RESEARCH INSTITUTE · PI CHAN, ANDREW T, MCNEIL, JOHN JAMES · 2019 to 2023
$42.9M
Genetics of Sessile Serrated PolypsK23DK103119 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI GALA, MANISH · 2014 to 2018
$960k
NIA NIH HHS U01 AG029824NIA NIH HHS U19 AG062682NIDDK NIH HHS K23 DK103119
6 · The paper itself

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.

Indexed as

Colorectal NeoplasmsDNA GlycosylasesAgedAspirinFemaleGenetic Predisposition to DiseaseGenomicsHumansMaleMutationProspective StudiesAspirinDNA Glycosylases

Identifiers

PMID35609203
PMCPMC9356994
OpenAlexW4282920046

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.