Evidence map›Paper›PMID 32107660›Full record

ArticleFamilial cancer2020

Do the risks of Lynch syndrome-related cancers depend on the parent of origin of the mutation?

Shimelis Dejene Gemechu, Christine M van Vliet, Aung Ko Win, Jane C Figueiredo, Loic Le Marchand, Steven Gallinger, Polly A Newcomb, John L Hopper, Noralane M Lindor, Mark A Jenkins and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Familial cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

11 authors.

Shimelis Dejene GemechuCentre for Epidemiology and Biostatistics, University of Melbourne, Parkville, VIC, Australia.
Christine M van VlietCentre for Epidemiology and Biostatistics, University of Melbourne, Parkville, VIC, Australia.
Aung Ko WinCentre for Epidemiology and Biostatistics, University of Melbourne, Parkville, VIC, Australia.
Jane C FigueiredoSamuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Loic Le MarchandUniversity of Hawaii Cancer Center, Honolulu, Hawaii, USA.
Steven GallingerMount Sinai Hospital, Lunenfeld Tanenbaum Research Institute, University of Toronto, Toronto, ON, Canada.
Polly A NewcombPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
John L HopperCentre for Epidemiology and Biostatistics, University of Melbourne, Parkville, VIC, Australia.
Noralane M LindorDepartment of Health Science Research, Mayo Clinic Arizona, Scottsdale, AZ, USA.
Mark A JenkinsCentre for Epidemiology and Biostatistics, University of Melbourne, Parkville, VIC, Australia.
James G DowtyCentre for Epidemiology and Biostatistics, University of Melbourne, Parkville, VIC, Australia. jdowty@unimelb.edu.au.ORCID 0000-0003-2383-0886

Funding

USC Consortium:Colorectal Cancer Family RegistryU01CA074799 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HAILE, ROBERT WILLIAM · 1997 to 2008
$20.4M
Data sharing: the Colon Cancer Family Registry CohortU01CA167551 · NCI · UNIVERSITY OF MELBOURNE · PI Daniel David BUCHANAN, Steven Gallinger · 2018 to 2026
$16.8M
SEATTLE FAMILIAL COLORECTAL CANCER REGISTRYU01CA074794 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI NEWCOMB, POLLY A · 1997 to 2007
$14.1M
ONTARIO REGISTRY FOR STUDIES OF FAMILIAL COLON CANCERU01CA074783 · NCI · CANCER CARE ONTARIO · PI GALLINGER, STEVEN · 1997 to 2008
$12.5M
Ethnic/Racial Minorities in the Colon CFRR01CA104132 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI LE MARCHAND, LOIC · 2004 to 2008
$9.5M
FAMILIAL COLORECTAL NEOPLASIA COLLABORATIVE GROUPU01CA074800 · NCI · MAYO CLINIC ROCHESTER · PI LINDOR, NORALANE MOREY · 1997 to 2007
$9.1M
The Colon Cancer Family Registry: USC ConsortiumU24CA074799 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HAILE, ROBERT WILLIAM · 2008 to 2011
$7.6M
The Colon Cancer Family Registry: SeattleU24CA074794 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI NEWCOMB, POLLY A · 2008 to 2011
$7.0M
AUSTRALASIAN COLORECTAL CANCER FAMILY REGISTRYU01CA097735 · NCI · UNIVERSITY OF MELBOURNE · PI HOPPER, JOHN L · 2002 to 2007
$6.9M
The Colon Cancer Family Registry: AustralasiaU24CA097735 · NCI · UNIVERSITY OF MELBOURNE · PI HOPPER, JOHN L · 2008 to 2011
$6.2M
HAWAII FAMILY REGISTRY OF COLON CANCERU01CA074806 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI LE MARCHAND, LOIC · 1997 to 2008
$6.1M
The Familial Colorectal Neoplasia Collaborative GroupU24CA074800 · NCI · MAYO CLINIC ROCHESTER · PI LINDOR, NORALANE MOREY, THIBODEAU, STEPHEN NORMAN · 2008 to 2011
$5.3M
NCI NIH HHS HHSN261201000035CNCI NIH HHS HHSN261201000035INCI NIH HHS HHSN261201000140CNCI NIH HHS HHSN261201300012INCI NIH HHS N01 CN067009NCI NIH HHS N01 PC035137NCI NIH HHS N01 PC035142NCI NIH HHS R01 CA104132NCI NIH HHS U01 CA074783NCI NIH HHS U01 CA074794NCI NIH HHS U01 CA074799NCI NIH HHS U01 CA074800NCI NIH HHS U01 CA074806NCI NIH HHS U01 CA097735NCI NIH HHS U01 CA167551NCI NIH HHS U24 CA074783NCI NIH HHS U24 CA074794NCI NIH HHS U24 CA074799NCI NIH HHS U24 CA074800NCI NIH HHS U24 CA074806NCI NIH HHS U24 CA097735
6 · The paper itself

Abstract

Individuals who carry pathogenic mutations in DNA mismatch repair (MMR) genes have high risks of cancer, and small studies have suggested that these risks depend on the sex of the parent from whom the mutation was inherited. We have conducted the first large study of such a parent-of-origin effect (POE). Our study was based on all MMR gene mutation carriers and their relatives in the Colon Cancer Family Registry, comprising 18,226 people. The POE was estimated as a hazard ratio (HR) using a segregation analysis approach that adjusted for ascertainment. HR = 1 corresponds to no POE and HR > 1 corresponds to higher risks for maternal mutations. For all MMR genes combined, the estimated POE HRs were 1.02 (95% confidence interval (CI) 0.75-1.39, p = 0.9) for male colorectal cancer, 1.12 (95% CI 0.81-1.54, p = 0.5) for female colorectal cancer and 0.84 (95% CI 0.52-1.36, p = 0.5) for endometrial cancer. Separate results for each MMR gene were similar. Therefore, despite being well-powered, our study did not find any evidence that cancer risks for MMR gene mutation carriers depend on the parent-of-origin of the mutation. Based on current evidence, we do not recommend that POEs be incorporated into the clinical guidelines or advice for such carriers.

Indexed as

DNA Mismatch RepairMutationParentsSex FactorsAdultAllelesColonic NeoplasmsColorectal NeoplasmsColorectal Neoplasms, Hereditary NonpolyposisDNA-Binding ProteinsEndometrial NeoplasmsFemaleGenetic Carrier ScreeningHeterozygoteHumansLogistic ModelsDNA-Binding ProteinsG-T mismatch-binding proteinMismatch Repair Endonuclease PMS2MLH1 protein, humanMSH2 protein, humanMutL Protein Homolog 1MutS Homolog 2 ProteinPMS2 protein, humanColorectal cancerEndometrial cancerLynch syndromeMismatch repair genesParent-of-origin effect

Identifiers

PMID32107660
PMCPMC7410789

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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.