Evidence map›Paper›PMID 25781442›Full record

ArticleJAMA2015

Association of aspirin and NSAID use with risk of colorectal cancer according to genetic variants.

Hongmei Nan, Carolyn M Hutter, Yi Lin, Eric J Jacobs, Cornelia M Ulrich, Emily White, John A Baron, Sonja I Berndt, Hermann Brenner, Katja Butterbach and 45 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JAMA, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
105citing papers in PubMed, 7 pooled it
29.3field-weighted citation impact, top 1% 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

105 citing papers in PubMed, 7 syntheses or guidelines pooled it, 201 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Aspirin and the Primary Prevention of Cardiovascular Diseases: An Approach Based on Individualized, Integrated Estimation of Risk.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2017
    Guideline
  5. Pooled it
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  8. Trial
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  12. Review
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  15. Article
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  17. Recalibrating the Genetics and Epidemiology of Colorectal Cancer Consortium Environmental Risk Score for Use in US Veterans.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2024
    Article
  18. Review
  19. Article
  20. Review

45 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

55 authors at 20 institutions in 6 countries.

Hongmei NanDepartment of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis2Indiana University Melvin and Bren Simon Cancer Center, Indianapolis.
Carolyn M HutterNational Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland.
Yi LinPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Eric J JacobsEpidemiology Research Program, American Cancer Society, Atlanta, Georgia.
Cornelia M UlrichPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington6Huntsman Cancer Institute, University of Utah, Salt Lake City.
Emily WhitePublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington7Department of Epidemiology, University of Washington School of Public Health, Seattle.
John A BaronDivision of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill.
Sonja I BerndtDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Hermann BrennerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany11German Cancer Consortium (DKTK), Heidelberg, Germany.
Katja ButterbachDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Bette J CaanDivision of Research, Kaiser Permanente Medical Care Program of Northern California, Oakland.
Peter T CampbellEpidemiology Research Program, American Cancer Society, Atlanta, Georgia.
Christopher S CarlsonPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Graham CaseyDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles.
Jenny Chang-ClaudeDivision of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
Stephen J ChanockDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Michelle CotterchioPrevention and Cancer Control, Cancer Care Ontario, Toronto, Ontario, Canada.
David DugganGenetic Basis of Human Disease Division, Translational Genomics Research Institute (TGen), Phoenix, Arizona.
Jane C FigueiredoDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles.
Charles S FuchsDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts.
Edward L GiovannucciChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massacusetts.
Jian GongPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Robert W HaileDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles.
Tabitha A HarrisonPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Richard B HayesDivision of Epidemiology, Department of Population Health, New York University School of Medicine, New York, New York.
Michael HoffmeisterDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
John L HopperMelbourne School of Population Health, University of Melbourne, Victoria, Australia.
Thomas J HudsonDepartment of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada22Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
Mark A JenkinsMelbourne School of Population Health, University of Melbourne, Victoria, Australia.
Shuo JiaoPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Noralane M LindorDepartment of Health Sciences Research, Mayo Clinic, Scottsdale, Arizona.
Mathieu LemireOntario Institute for Cancer Research, Toronto, Ontario, Canada.
Loic Le MarchandEpidemiology Program, University of Hawaii Cancer Center, Honolulu.
Polly A NewcombPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Shuji OginoDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts25Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts26Department of Epidemiology, Harvard School of Public Health, Boston, Masschusetts.
Bethann M PflugeisenPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
John D PotterPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington27Centre for Public Health Research, Massey University, Wellington, New Zealand.
Conghui QuPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Stephanie A RossePublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Anja RudolphDivision of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
Robert E SchoenDepartment of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Fredrick R SchumacherDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles.
Daniela SeminaraNational Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland.
Martha L SlatteryDepartment of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City.
Stephen N ThibodeauDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota31Department of Medical Genetics, Mayo Clinic, Rochester, Minnesota.
Fridtjof ThomasDivision of Biostatistics and Epidemiology, Department of Preventive Medicine, University of Tennessee Healthy Science Center, Memphis.
Mark ThornquistPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Greg S WarnickPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Brent W ZankeClinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
W James GaudermanDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles.
Ulrike PetersPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington7Department of Epidemiology, University of Washington School of Public Health, Seattle.
Li HsuPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington34Department of Biostatistics, University of Washington, Seattle.
Andrew T ChanChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massacusetts35Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
CCFR
GECCO
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa · ZAUniversity of Southern California · USFred Hutch Cancer Center · USHeidelberg University · DENational Institutes of Health · USAmerican Cancer Society · USBrigham and Women's Hospital · USGerman Cancer Research Center · DEOntario Institute for Cancer Research · CAThe University of Melbourne · AUUniversity of Washington · USCancer Care Ontario · CADana-Farber Brigham Cancer Center · USDana-Farber Cancer Institute · USHuntsman Cancer Institute · USIndiana University Health · USKaiser Permanente · USMayo Clinic · USMayo Clinic in Arizona · USNational Cancer Institute · US

Funding

Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3M
Statistical MethodsP01CA087969 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI TWOROGER, SHELLEY S · 2000 to 2019
$77.8M
University of Hawaii Cancer Center CCSGP30CA071789 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI Xin Chen · 1996 to 2026
$56.2M
Validity of Diet and Activity Measures in WomenP01CA055075 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI WILLETT, WALTER C. · 1991 to 2009
$41.8M
Tissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI EL-BARDEESY, NABEEL, SELLERS, WILLIAM R · 2007 to 2023
$33.2M
Molecular pathological epidemiology of colorectal cancerU01CA137088 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PETERS, ULRIKE · 2009 to 2018
$21.8M
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
Detection of Colorectal Cancer Susceptibility Loci Using Genome-Wide SequencingU01CA164930 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PETERS, ULRIKE · 2012 to 2015
$12.4M
Cancer Epidemiology Cohort in Male Health ProfessionalsUM1CA167552 · NCI · HARVARD SCHOOL OF PUBLIC HEALTH · PI WILLETT, WALTER C. · 2012 to 2016
$11.5M
Genome-Wide Association Study of Nonsynonymous SNPs in Colon CancerR01CA059045 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PETERS, ULRIKE · 1994 to 2011
$11.5M
Colon Cancer Family Registry CohortUM1CA167551 · NCI · STANFORD UNIVERSITY · PI HAILE, ROBERT WILLIAM, JENKINS, MARK A · 2013 to 2017
$11.3M
CIHRIntramural NIH HHSNCI NIH HHS K05 CA154337NCI NIH HHS P01 CA053996NCI NIH HHS P01 CA 055075NCI NIH HHS P01 CA055075NCI NIH HHS P01 CA 087969NCI NIH HHS P01 CA087969NCI NIH HHS P30 CA015083NCI NIH HHS P30 CA071789NCI NIH HHS P50 CA 127003NCI NIH HHS P50 CA127003NCI NIH HHS R01 CA048998NCI NIH HHS R01 CA059045NCI NIH HHS R01 CA076366NCI NIH HHS R01 CA137178NCI NIH HHS R01 CA151993NCI NIH HHS R01 CA48998NCI NIH HHS RFA CA-95-011NCI NIH HHS U01 CA074783NCI NIH HHS U01 CA074794NCI NIH HHS U01 CA097735NCI NIH HHS U01 CA122839NCI NIH HHS U01 CA137088NCI NIH HHS U01 CA164930NCI NIH HHS U24 CA074783NCI NIH HHS U24 CA074794NCI NIH HHS U24 CA097735NCI NIH HHS UM1 CA167551NCI NIH HHS UM1 CA167552NHLBI NIH HHS HHSN268201100001INHLBI NIH HHS HHSN268201100002INHLBI NIH HHS HHSN268201100003INHLBI NIH HHS HHSN268201100004INHLBI NIH HHS HHSN268201100046CNIA NIH HHS HHSN271201100004CNIDDK NIH HHS K24 DK098311PHS HHS R01 137178WHI NIH HHS HHSN268201100001CWHI NIH HHS HHSN268201100002CWHI NIH HHS HHSN268201100003CWHI NIH HHS HHSN268201100004C
6 · The paper itself

Abstract

importanceUse of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with lower risk of colorectal cancer.

objectiveTo identify common genetic markers that may confer differential benefit from aspirin or NSAID chemoprevention, we tested gene × environment interactions between regular use of aspirin and/or NSAIDs and single-nucleotide polymorphisms (SNPs) in relation to risk of colorectal cancer. DESIGN, SETTING, AND

participantsCase-control study using data from 5 case-control and 5 cohort studies initiated between 1976 and 2003 across the United States, Canada, Australia, and Germany and including colorectal cancer cases (n=8634) and matched controls (n=8553) ascertained between 1976 and 2011. Participants were all of European descent. EXPOSURES: Genome-wide SNP data and information on regular use of aspirin and/or NSAIDs and other risk factors. MAIN OUTCOMES AND MEASURES: Colorectal cancer.

resultsRegular use of aspirin and/or NSAIDs was associated with lower risk of colorectal cancer (prevalence, 28% vs 38%; odds ratio [OR], 0.69 [95% CI, 0.64-0.74]; P = 6.2 × 10(-28)) compared with nonregular use. In the conventional logistic regression analysis, the SNP rs2965667 at chromosome 12p12.3 near the MGST1 gene showed a genome-wide significant interaction with aspirin and/or NSAID use (P = 4.6 × 10(-9) for interaction). Aspirin and/or NSAID use was associated with a lower risk of colorectal cancer among individuals with rs2965667-TT genotype (prevalence, 28% vs 38%; OR, 0.66 [95% CI, 0.61-0.70]; P = 7.7 × 10(-33)) but with a higher risk among those with rare (4%) TA or AA genotypes (prevalence, 35% vs 29%; OR, 1.89 [95% CI, 1.27-2.81]; P = .002). In case-only interaction analysis, the SNP rs16973225 at chromosome 15q25.2 near the IL16 gene showed a genome-wide significant interaction with use of aspirin and/or NSAIDs (P = 8.2 × 10(-9) for interaction). Regular use was associated with a lower risk of colorectal cancer among individuals with rs16973225-AA genotype (prevalence, 28% vs 38%; OR, 0.66 [95% CI, 0.62-0.71]; P = 1.9 × 10(-30)) but was not associated with risk of colorectal cancer among those with less common (9%) AC or CC genotypes (prevalence, 36% vs 39%; OR, 0.97 [95% CI, 0.78-1.20]; P = .76). CONCLUSIONS AND RELEVANCE: In this genome-wide investigation of gene × environment interactions, use of aspirin and/or NSAIDs was associated with lower risk of colorectal cancer, and this association differed according to genetic variation at 2 SNPs at chromosomes 12 and 15. Validation of these findings in additional populations may facilitate targeted colorectal cancer prevention strategies.

Indexed as

Gene-Environment InteractionPolymorphism, Single NucleotideAnti-Inflammatory Agents, Non-SteroidalAspirinCase-Control StudiesChromosomes, Human, Pair 12Chromosomes, Human, Pair 15Colorectal NeoplasmsFemaleGenetic MarkersGenotypeHumansMaleRisk FactorsAnti-Inflammatory Agents, Non-SteroidalAspirinGenetic Markers

Identifiers

PMID25781442
PMCPMC4382867
OpenAlexW2082035590

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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.