ArticlePLoS genetics2016
Genome-Wide Interaction Analyses between Genetic Variants and Alcohol Consumption and Smoking for Risk of Colorectal Cancer.
Registry-linked trialOpen access · goldAbstract read
In one paragraph
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02328677 (ColoCare Transdisciplinary Research in Colorectal Cancer Prognosis), which is not on this map. Cited by 36 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 3 pooled it
5.1field-weighted citation impact, top 5% of its field
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.
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.
ColoCare Transdisciplinary Research in Colorectal Cancer Prognosis
Who cites it
36 citing papers in PubMed, 3 syntheses or guidelines pooled it, 43 citations in OpenAlex.
- Alcohol consumption, DNA methylation and colorectal cancer risk: Results from pooled cohort studies and Mendelian randomization analysis.International journal of cancer · 2022Pooled it
- Meta-analysis of 16 studies of the association of alcohol with colorectal cancer.International journal of cancer · 2020Pooled it
- Gene-environment interactions and colorectal cancer risk: An umbrella review of systematic reviews and meta-analyses of observational studies.International journal of cancer · 2019Pooled it
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- TGF-β Pathway-Based Polygenic Risk Score Modifies the Association between Red Meat Intake and Colorectal Cancer Risk: Application of a Novel Pathway-Based PRS Method.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026Article
- Alcohol consumption and molecular subtypes of colorectal cancer: pooled observational and Mendelian randomization analyses.The American journal of clinical nutrition · 2026Observational
- Red meat intake interacts with a TGF-β-pathway-based polygenic risk score to impact colorectal cancer risk: Application of a novel approach for polygenic risk score construction.medRxiv : the preprint server for health sciences · 2025Article
- Decoding the genetic and environmental forces in propelling the surge of early-onset colorectal cancer.Chinese medical journal · 2025Review
- Characterization of Additive Gene-environment Interactions For Colorectal Cancer Risk.Epidemiology (Cambridge, Mass.) · 2025Article
- Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk.British journal of cancer · 2024Article
- Epidemiologic Factors in Relation to Colorectal Cancer Risk and Survival by Genotoxic Colibactin Mutational Signature.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2024Article
- Genome-Wide Gene-Environment Interaction Analyses to Understand the Relationship between Red Meat and Processed Meat Intake and Colorectal Cancer Risk.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2024Article
- Genome-Wide Interaction Study of Dietary Intake and Colorectal Cancer Risk in the UK Biobank.JAMA network open · 2024Article
- Genome-wide interaction analysis of folate for colorectal cancer risk.The American journal of clinical nutrition · 2023Article
- Genome-wide Interaction Study with Smoking for Colorectal Cancer Risk Identifies Novel Genetic Loci Related to Tumor Suppression, Inflammation, and Immune Response.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2023Article
- Article
- Genome-Wide Interaction Analysis of Genetic Variants With Menopausal Hormone Therapy for Colorectal Cancer Risk.Journal of the National Cancer Institute · 2022Article
- Beyond GWAS of Colorectal Cancer: Evidence of Interaction with Alcohol Consumption and Putative Causal Variant for the 10q24.2 Region.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2022Article
- Article
- Traumatic events during childhood and its risks to substance use in adulthood: an observational and genome-wide by environment interaction study in UK Biobank.Translational psychiatry · 2021Observational
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
49 authors at 20 institutions in 6 countries.
Jian GongPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
Carolyn M HutterDivision of Genomic Medicine, National Human Genome Research Institute, Bethesda, Maryland, United States of America.
Polly A NewcombPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
Cornelia M UlrichPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.ORCID http://orcid.org/0000-0001-7641-059X
Stephanie A BienPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.ORCID http://orcid.org/0000-0002-8713-4583
Peter T CampbellEpidemiology Research Program, American Cancer Society, Atlanta, Georgia, United States of America.
John A BaronDepartment of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
Sonja I BerndtDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America.
Stephane BezieauCHU Nantes, Service de Génétique Médicale, Nantes, France.
Hermann BrennerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Graham CaseyKeck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
Andrew T ChanDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
Jenny Chang-ClaudeDivision of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
Mengmeng DuPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
David DugganTranslational Genomics Research Institute, Phoenix, Arizona, United States of America.ORCID http://orcid.org/0000-0002-4696-3940
Jane C FigueiredoKeck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
Steven GallingerDepartment of Surgery, University Health Network Toronto General Hospital, Toronto, Ontario, Canada.
Edward L GiovannucciChanning Division of Network Medicine, Brigham and Women's Hospital, Boston Massachusetts, United States of America.
Robert W HaileKeck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
Tabitha A HarrisonPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
Richard B HayesDivision of Epidemiology, New York University School of Medicine, New York, New York, United States of America.
Michael HoffmeisterDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
John L HopperMelbourne School of Population Health, The University of Melbourne, Melbourne, Australia.
Thomas J HudsonOntario Institute for Cancer Research, Toronto, Ontario, Canada.
Jihyoun JeonPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
Mark A JenkinsMelbourne School of Population Health, The University of Melbourne, Melbourne, Australia.
Jonathan KocarnikPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.ORCID http://orcid.org/0000-0001-8084-1608
Sébastien KüryCHU Nantes, Service de Génétique Médicale, Nantes, France.
Loic Le MarchandEpidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, United States of America.
Yi LinPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
Noralane M LindorDepartment of Health Sciences Research, Mayo Clinic, Scottsdale, Arizona, United States of America.
Reiko NishiharaDana-Farber Cancer Institute, Harvard School of Public Health, Boston, Massachusetts, United States of America.
Shuji OginoHarvard Medical School, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America.
John D PotterPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
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, United States of America.
Petra Schrotz-KingDivision of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-2397-9480
Daniela SeminaraDivision of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland, United States of America.
Martha L SlatteryDepartment of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah, United States of America.
Stephen N ThibodeauDepartments of Laboratory Medicine and Pathology and Laboratory Genetics, Mayo Clinic, Rochester, Minnesota, United States of America.
Mark ThornquistPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
Reka TothDivision of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany.
Robert WallaceDepartment of Epidemiology, The University of Iowa, Iowa City, Iowa, United States of America.
Emily WhitePublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
Shuo JiaoPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
Mathieu LemireOntario Institute for Cancer Research, Toronto, Ontario, Canada.
Li HsuPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
Ulrike PetersPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
CCFR and GECCO
Fred Hutch Cancer Center · USGerman Cancer Research Center · DEUniversity of Southern California · USBrigham and Women's Hospital · USGénétique Médicale & Génomique Fonctionelle · FRNational Cancer Institute · USOntario Institute for Cancer Research · CAThe University of Melbourne · AUUniversity of Utah · USAmerican Cancer Society · USDana-Farber Cancer Institute · USHarvard University · USMayo Clinic · USMayo Clinic in Arizona · USNational Human Genome Research Institute · USNew York University · USTranslational Genomics Research Institute · USUniversity Health Network · CAUniversity of Hawaiʻi at Mānoa · USUniversity of Iowa · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MWomen's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI AKHILESH PANDEY · 1985 to 2026
$151.3MStatistical MethodsP01CA087969 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ROSNER, BERNARD A · 2000 to 2019
$77.8MUniversity of Hawaii Cancer Center CCSGP30CA071789 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI GERTRAUD MASKARINEC · 1996 to 2026
$56.2MValidity of Diet and Activity Measures in WomenP01CA055075 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI RIMM, ERIC B · 1991 to 2009
$41.8MTissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI BASS, ADAM JOEL · 2007 to 2023
$33.2MPLCO Trial Etiologic and Early Marker StudyZIACP010152 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI MOORE, STEVEN · 2009 to 2025
$29.9MJH/CIDR Genotyping for Genome-Wide Association StudiesU01HG004438 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2007 to 2011
$24.2MGENETIC SUSCEPTIBILITY TO CANCER IN MULTIETHNIC COHORTSR01CA063464 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HENDERSON, BRIAN E · 2001 to 2005
$23.2MMultiethnic Cohort Study of Diet and CancerR37CA054281 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI KOLONEL, LAURENCE N. · 2003 to 2012
$23.2MLong Term Multidisciplinary Study of Cancer in Women: The Nurses Health StudyUM1CA186107 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER, STAMPFER, MEIR · 2014 to 2023
$22.3MMolecular pathological epidemiology of colorectal cancerU01CA137088 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PETERS, ULRIKE · 2009 to 2018
$21.8MIntramural NIH HHS Z01 CP010200NCI NIH HHS K05 CA152715NCI NIH HHS K05 CA154337NCI NIH HHS K07 CA190673NCI NIH HHS P01 CA033619NCI NIH HHS P01 CA055075NCI NIH HHS P01 CA087969NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA015083NCI NIH HHS P30 CA071789NCI NIH HHS P50 CA127003NCI NIH HHS R01 CA042182NCI NIH HHS R01 CA048998NCI NIH HHS R01 CA059045NCI NIH HHS R01 CA060987NCI NIH HHS R01 CA063464NCI NIH HHS R01 CA076366NCI NIH HHS R01 CA120582NCI NIH HHS R01 CA137178NCI NIH HHS R01 CA143237NCI NIH HHS R01 CA151993NCI NIH HHS R01 CA195789NCI NIH HHS R35 CA197735NCI NIH HHS R37 CA054281NCI 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 U01 CA206110NCI NIH HHS U24 CA074783NCI NIH HHS U24 CA074794NCI NIH HHS U24 CA097735NCI NIH HHS UM1 CA167551NCI NIH HHS UM1 CA167552NCI NIH HHS UM1 CA186107NHGRI NIH HHS U01 HG004438NHGRI NIH HHS U01 HG004446NHLBI NIH HHS HHSN268201100001INHLBI NIH HHS HHSN268201100002INHLBI NIH HHS HHSN268201100003INHLBI NIH HHS HHSN268201100004INHLBI NIH HHS HHSN268201100046CNIA NIH HHS HHSN271201100004CWHI NIH HHS HHSN268201100001CWHI NIH HHS HHSN268201100002CWHI NIH HHS HHSN268201100003CWHI NIH HHS HHSN268201100004C
Abstract
Genome-wide association studies (GWAS) have identified many genetic susceptibility loci for colorectal cancer (CRC). However, variants in these loci explain only a small proportion of familial aggregation, and there are likely additional variants that are associated with CRC susceptibility. Genome-wide studies of gene-environment interactions may identify variants that are not detected in GWAS of marginal gene effects. To study this, we conducted a genome-wide analysis for interaction between genetic variants and alcohol consumption and cigarette smoking using data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Interactions were tested using logistic regression. We identified interaction between CRC risk and alcohol consumption and variants in the 9q22.32/HIATL1 (Pinteraction = 1.76×10-8; permuted p-value 3.51x10-8) region. Compared to non-/occasional drinking light to moderate alcohol consumption was associated with a lower risk of colorectal cancer among individuals with rs9409565 CT genotype (OR, 0.82 [95% CI, 0.74-0.91]; P = 2.1×10-4) and TT genotypes (OR,0.62 [95% CI, 0.51-0.75]; P = 1.3×10-6) but not associated among those with the CC genotype (p = 0.059). No genome-wide statistically significant interactions were observed for smoking. If replicated our suggestive finding of a genome-wide significant interaction between genetic variants and alcohol consumption might contribute to understanding colorectal cancer etiology and identifying subpopulations with differential susceptibility to the effect of alcohol on CRC risk.
Indexed as
AgedAlcohol DrinkingColorectal NeoplasmsFemaleGene-Environment InteractionGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansMaleMembrane Transport ProteinsMiddle AgedPolymorphism, Single NucleotideRisk FactorsSmokingTumor Suppressor ProteinsMembrane Transport ProteinsMFSD14B protein, humanTumor Suppressor Proteins
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NCT02328677ClinicalTrials.gov
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.