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, Xiao Ou Shu, Wanqing Wen, Peter Kraft, Sara Lindström, Ulrike Peters, Joellen Schildkraut, Fredrick Schumacher, Paolo Bofetta, Angela Risch, Heike Bickeböller, Christopher I. Amos, Douglas Easton, Rosalind A. Eeles, Stephen B. Gruber, Christopher A. Haiman, David J. Hunter, Stephen J. Chanock, Brandon L. Pierce, Wei Zheng*Kendra Blalock, Peter T. Campbell, Graham Casey, David V. Conti, Christopher K. Edlund, Jane Figueiredo, W. James Gauderman, Jian Gong, Roger C. Green, John F. Harju, Tabitha A. Harrison, Eric J. Jacobs, Mark A. Jenkins, Shuo Jiao, Li Li, Yi Lin, Frank J. Manion, Victor Moreno, Bhramar Mukherjee, Leon Raskin, Fredrick R. Schumacher, Daniela Seminara, Gianluca Severi, Stephanie L. Stenzel, Duncan C. Thomas, John L. Hopper, Melissa C. Southey, Enes Makalic, Daniel F. Schmidt, Olivia Fletcher, Julian Peto, Lorna Gibson, Isabel dos Santos Silva, Habib Ahsan, Alice Whittemore, Quinten Waisfisz, Hanne Meijers-Heijboer, Muriel Adank, Rob B. van der Luijt, Andre G. Uitterlinden, Albert Hofman, Alfons Meindl, Rita K. Schmutzler, Bertram Müller-Myhsok, Peter Lichtner, Heli Nevanlinna, Taru A. Muranen, Kristiina Aittomäki, Carl Blomqvist, Jenny Chang-Claude, Rebecca Hein, Norbert Dahmen, Lars Beckman, Laura Crisponi, Per Hall, Kamila Czene, Astrid Irwanto, Jianjun Liu, Douglas F. Easton, Clare Turnbull, Nazneen Rahman, Rosalind Eeles, Zsofia Kote-Jarai, Kenneth Muir, Graham Giles, David Neal, Jenny L. Donovan, Freddie C. Hamdy, Fredrik Wiklund, Henrik Gronberg, Christopher Haiman, Fred Schumacher, Ruth Travis, Elio Riboli, David Hunter, Susan Gapstur, Sonja Berndt, Stephen Chanock, Younghun Han, Li Su, Yongyue Wei, Rayjean J. Hung, Yonathan Brhane, John McLaughlin, Paul Brennan, James D. McKay, Albert Rosenberger, Richard S. Houlston, Neil Caporaso, Maria Teresa Landi, Joachim Heinrich, Xifeng Wu, Yuanqing Ye, David C. Christiani

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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 - 1 Sep 2016

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