Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses.
BACKGROUND
Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS), to evaluate the association of adult height with these cancers.


RESULTS
A systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15), 1.07 (95% CI 1.05, 1.10), and 1.06 (95% CI 1.02, 1.11) for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18) and lung cancer (OR = 1.10, 95% CI 1.00, 1.22) associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15). Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate.


CONCLUSIONS
Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the risk of these cancers.
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Nikhil K
NK
Khankari
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Xiao-Ou
XO
Shu
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Wanqing
W
Wen
Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.
Peter
P
Kraft
Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.
Sara
S
Lindström
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
Ulrike
U
Peters
Cancer Prevention, Detection & Control Research Program, Duke Cancer Institute, Durham, North Carolina, United States of America.
Joellen
J
Schildkraut
Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, United States of America.
Fredrick
F
Schumacher
Tisch Cancer Institute and Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Paolo
P
Bofetta
Division of Cancer Genetics/Epigenetics, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.|Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Translational Lung Research Center Heidelberg, German Center for Lung Research (DZL), Heidelberg, Germany.
Angela
A
Risch
Department of Genetic Epidemiology, University Medical Center, Georg-August-Universität Göttingen, Göttingen, Germany.
Heike
H
Bickeböller
Center for Genomic Medicine, Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire, United States of America.
Christopher I
CI
Amos
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
Douglas
D
Easton
Institute of Cancer Research, London, United Kingdom.|Royal Marsden NHS Foundation Trust, London, United Kingdom.
Rosalind A
http://orcid.org/0000-0002-7472-5384
RA
Eeles
USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, United States of America.
Stephen B
SB
Gruber
USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, United States of America.|Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
Christopher A
CA
Haiman
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.
David J
DJ
Hunter
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
Stephen J
SJ
Chanock
Department of Public Health Studies, University of Chicago, Chicago, Illinois, United States of America.
Brandon L
BL
Pierce
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Wei
W
Zheng
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001827:Body Height; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000235:genetics; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D016017:Odds Ratio; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000453:epidemiology* / Q000235:genetics; D012307:Risk Factors; D055815:Young Adult