Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses

Nikhil K. Khankari, the Colorectal Transdisciplinary Study (CORECT), Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE), Transdisciplinary Research in Cancer of the Lung (TRICL), Transdisciplinary Research in Cancer of the Lung (TRICL), Xiao Ou Shu, Wanqing Wen, Peter Kraft, Sara Lindström, Ulrike Peters, Joellen Schildkraut, Fredrick R. Schumacher, Paolo Bofetta, Angela Risch, Heike Bickeböller, Christopher I. Amos, Douglas F. Easton, Rosalind A. Eeles, Stephen B. Gruber, Christopher A. HaimanDavid J. Hunter, Stephen J. Chanock, Brandon L. Pierce, Wei Zheng*, Li Li, Hanne Meijers-Heijboer, Muriel Adank, Andre G. Uitterlinden, Albert Hofman, Joachim Heinrich

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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. Methods and Findings: 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.

Original languageEnglish
Article numbere1002118
JournalPLoS Medicine
Volume13
Issue number9
DOIs
Publication statusPublished - Sept 2016

Bibliographical note

Funding:
The work for this project at Vanderbilt
University was supported primarily by US NIH (http://
www.nih.gov) grant R37CA070867 and by funds from
the Ingram Professorship and Anne Potter Wilson
endowments. NKK was supported by NIH grant
R25CA160056-03. The Post-Cancer GWAS (GAMEON) initiative was supported by NIH grants
U19CA148065 (DRIVE, PI: DJH), U19CA148107
(CORECT, PI: SBG), U19CA148127 (TRICL, PI: CIA), and U19CA148537 (ELLIPSE, PI: CAH). RAE
is supported by Cancer Research UK (http://www.
cancerresearchuk.org/), Prostate Cancer UK (http://
prostatecanceruk.org/), The Institute of Cancer
Research (http://www.icr.ac.uk/), and Royal Marsden
Biomedical Research Centre, which receives support
from the National Institute of Health Research (http://
www.nihr.ac.uk) (C5047/A17528). The funders had
no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2016 This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.

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