Evidence map›Paper›PMID 27427428›Full record

ArticleInternational journal of epidemiology2016

Mendelian randomization study of adiposity-related traits and risk of breast, ovarian, prostate, lung and colorectal cancer.

Chi Gao, Chirag J Patel, Kyriaki Michailidou, Ulrike Peters, Jian Gong, Joellen Schildkraut, Fredrick R Schumacher, Wei Zheng, Paolo Boffetta, Isabelle Stucker and 13 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of epidemiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed, 10 pooled it
9.5field-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

98 citing papers in PubMed, 10 syntheses or guidelines pooled it, 162 citations in OpenAlex.

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  7. Genetic Variation and Hot Flashes: A Systematic Review.The Journal of clinical endocrinology and metabolism · 2020
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38 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 12 institutions in 5 countries.

Chi GaoProgram in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Chirag J PatelDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Kyriaki MichailidouCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK, Department of Electron Microscopy/Molecular Pathology, Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus and.
Ulrike PetersPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Jian GongPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Joellen SchildkrautCancer Prevention, Detection & Control Research Program, Duke Cancer Institute, Durham, NC, USA, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
Fredrick R SchumacherDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Wei ZhengDepartment of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.
Paolo BoffettaTisch Cancer institute and Institute for Transitional Epidemiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Isabelle StuckerCentre for Research in Epidemiology and Population Health, INSERM, Villejuif, France.
Walter WillettDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA, Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Stephen GruberUSC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
Douglas F EastonCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK, Department of Oncology, University of Cambridge, Cambridge, UK.
David J HunterDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Thomas A SellersDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
Christopher HaimanDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Brian E HendersonDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Rayjean J HungLunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada.
Christopher AmosCenter for Genomic Medicine, Geisel School of Medicine, Dartmouth College, Lebanon, NH, USA.
Brandon L PierceDepartment of Public Health Studies, University of Chicago, Chicago, IL, USA.
Sara LindströmProgram in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Peter Kraft
the Colorectal Transdisciplinary Study (CORECT); Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE); Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE); Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI); and Transdisciplinary Research in Cancer of the Lung (TRICL)
Harvard University · USUniversity of Southern California · USFred Hutch Cancer Center · USUniversity of Cambridge · GBCentre de recherche en Epidémiologie et Santé des Populations · FRChicago Department of Public Health · USDartmouth College · USIcahn School of Medicine at Mount Sinai · USMoffitt Cancer Center · USMount Sinai Hospital · CAUniversity of Virginia · USVanderbilt University · US

Funding

Translational Engineering in Cancer (TEC)P30CA023108 · NCI · DARTMOUTH COLLEGE · PI Steven D Leach · 1985 to 2026
$91.3M
Transdisciplinary Studies of Genetic Variation in Colorectal CancerU19CA148107 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GRUBER, STEPHEN B · 2010 to 2014
$11.1M
Transdisciplinary Research in Cancer of the Lung (TRICL)U19CA148127 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI AMOS, CHRISTOPHER I., LE MARCHAND, LOIC · 2010 to 2014
$10.9M
Epidemiologic StudiesU19CA148065 · NCI · HARVARD SCHOOL OF PUBLIC HEALTH · PI AHSAN, HABIBUL, BRUGGE, JOAN SIEFERT · 2010 to 2014
$10.6M
Epidemiological and Clinical Translational Studies Post Genome-Wide AssociationU19CA148537 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI EASTON, DOUGLAS FREDERICK, EELES, ROSALIND · 2010 to 2014
$10.4M
Ovarian cancer GWAS discovery, expansion and replication (N2 - Project #1)U19CA148112 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI SELLERS, THOMAS A · 2010 to 2014
$10.2M
Haplotype-Based Genome Screen for Ovarian Cancer LociR01CA114343 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI SELLERS, THOMAS A · 2007 to 2011
$7.5M
Data-driven identification of environmental factors in cardiovascular diseaseR00ES023504 · NIEHS · HARVARD MEDICAL SCHOOL · PI PATEL, CHIRAG J. · 2016 to 2018
$728k
Increasing the power of GxE detection by using multi-locus genome-wide predictorsR21ES025052 · NIEHS · HARVARD MEDICAL SCHOOL · PI PATEL, CHIRAG J. · 2015 to 2017
$434k
Data-driven identification of environmental factors in cardiovascular diseaseK99ES023504 · NIEHS · HARVARD MEDICAL SCHOOL · PI PATEL, CHIRAG J. · 2014 to 2015
$245k
GWAS on childhood body fatness as an intermediate phenotype of breast cancerR03CA165131 · NCI · HARVARD SCHOOL OF PUBLIC HEALTH · PI LINDSTROEM, SARA · 2012 to 2013
$174k
Cancer Research UK 16563Cancer Research UK C1178/A3947Cancer Research UK C1287/A16563Cancer Research UK C150/A5660Cancer Research UK C490/A8339Medical Research Council MC_UU_12013/5NCI NIH HHS P30 CA023108NCI NIH HHS R01 CA114343NCI NIH HHS R03 CA165131NCI NIH HHS U19 CA148065NCI NIH HHS U19 CA148107NCI NIH HHS U19 CA148112NCI NIH HHS U19 CA148127NCI NIH HHS U19 CA148537NIEHS NIH HHS K99 ES023504NIEHS NIH HHS R00 ES023504NIEHS NIH HHS R21 ES025052Wellcome Trust 076113Wellcome Trust 085475
6 · The paper itself

Abstract

backgroundAdiposity traits have been associated with risk of many cancers in observational studies, but whether these associations are causal is unclear. Mendelian randomization (MR) uses genetic predictors of risk factors as instrumental variables to eliminate reverse causation and reduce confounding bias. We performed MR analyses to assess the possible causal relationship of birthweight, childhood and adult body mass index (BMI), and waist-hip ratio (WHR) on the risks of breast, ovarian, prostate, colorectal and lung cancers.

methodsWe tested the association between genetic risk scores and each trait using summary statistics from published genome-wide association studies (GWAS) and from 51 537 cancer cases and 61 600 controls in the Genetic Associations and Mechanisms in Oncology (GAME-ON) Consortium.

resultsWe found an inverse association between the genetic score for childhood BMI and risk of breast cancer [odds ratio (OR) = 0.71 per standard deviation (s.d.) increase in childhood BMI; 95% confidence interval (CI): 0.60, 0.80; P = 6.5 × 10(-5)). We also found the genetic score for adult BMI to be inversely associated with breast cancer risk (OR = 0.66 per s.d. increase in BMI; 95% CI: 0.57, 0.77; P = 2.5 × 10(-7)), and positively associated with ovarian cancer (OR = 1.35; 95% CI: 1.05, 1.72; P = 0.017), lung cancer (OR = 1.27; 95% CI: 1.09, 1.49; P = 2.9 × 10(-3)) and colorectal cancer (OR = 1.39; 95% CI: 1.06, 1.82, P = 0.016). The inverse association between genetically predicted adult BMI and breast cancer risk remained even after adjusting for directional pleiotropy via MR-Egger regression.

conclusionsFindings from this study provide additional understandings of the complex relationship between adiposity and cancer risks. Our results for breast and lung cancer are particularly interesting, given previous reports of effect heterogeneity by menopausal status and smoking status.

Indexed as

Body Mass IndexPolymorphism, Single NucleotideWaist-Hip RatioAdiposityBreast NeoplasmsColorectal NeoplasmsFemaleHumansLung NeoplasmsMaleMendelian Randomization AnalysisNeoplasmsOdds RatioOvarian NeoplasmsPhenotypeProstatic Neoplasmsbody mass indexCancer riskMendelian randomizationpost-GWAS studywaist-to-hip ratio

Identifiers

PMID27427428
PMCPMC6372135
OpenAlexW2483210912

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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.