Mendelian randomization study of height and risk of colorectal cancer

Aaron P Thrift; Jian Gong; Ulrike Peters; Jenny Chang-Claude; Anja Rudolph; Martha L Slattery; Andrew T Chan; Tonu Esko; Andrew R Wood; Jian Yang; Sailaja Vedantam; Stefan Gustafsson; Tune H Pers; GIANT Consortium; John A Baron; Stéphane Bezieau; Sébastien Küry; Shuji Ogino; Sonja I Berndt; Graham Casey; Robert W Haile; Mengmeng Du; Tabitha A Harrison; Mark Thornquist; David J Duggan; Loic Le Marchand; Mathieu Lemire; Noralane M Lindor; Daniela Seminara; Mingyang Song; Stephen N Thibodeau; Michelle Cotterchio; Aung Ko Win; Mark A Jenkins; John L Hopper; Cornelia M Ulrich; John D Potter; Polly A Newcomb; Robert E Schoen; Michael Hoffmeister; Hermann Brenner; Emily White; Li Hsu; Peter T Campbell

doi:10.1093/ije/dyv082

Mendelian randomization study of height and risk of colorectal cancer

Int J Epidemiol. 2015 Apr;44(2):662-72. doi: 10.1093/ije/dyv082. Epub 2015 May 20.

Authors

Aaron P Thrift¹, Jian Gong¹, Ulrike Peters¹, Jenny Chang-Claude¹, Anja Rudolph¹, Martha L Slattery¹, Andrew T Chan¹, Tonu Esko¹, Andrew R Wood¹, Jian Yang¹, Sailaja Vedantam¹, Stefan Gustafsson¹, Tune H Pers¹; GIANT Consortium; John A Baron¹, Stéphane Bezieau¹, Sébastien Küry¹, Shuji Ogino¹, Sonja I Berndt¹, Graham Casey¹, Robert W Haile¹, Mengmeng Du¹, Tabitha A Harrison¹, Mark Thornquist¹, David J Duggan¹, Loic Le Marchand¹, Mathieu Lemire¹, Noralane M Lindor¹, Daniela Seminara¹, Mingyang Song¹, Stephen N Thibodeau¹, Michelle Cotterchio¹, Aung Ko Win¹, Mark A Jenkins¹, John L Hopper¹, Cornelia M Ulrich¹, John D Potter¹, Polly A Newcomb¹, Robert E Schoen¹, Michael Hoffmeister¹, Hermann Brenner¹, Emily White¹, Li Hsu¹, Peter T Campbell¹

Affiliation

¹ Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA, Department of Medicine and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA, Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, UT, USA, Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA, Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, Estonian Genome Center, University of Tartu, Tartu, Estonia, Divisions of Endocrinology and Genetics and Center for Basic Translational Obesity Research, Boston Children's Hospital, Boston, MA, USA, Department of Genetics, Harvard Medical School, Boston, MA, USA, Broad Institute, Cambridge, MA, USA, Genetics of Complex Traits, University of Exeter Medical School, Exeter, UK, Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia, University of Queensland Diamantina Institute, Translation Research Institute, Brisbane, QLD, Australia, Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark, Department of Medical Sciences, Uppsala University, Uppsala, Sweden, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA, CHU Nantes, Service de Génétique Médicale, Nantes, France, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA, Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, USC Norris

Abstract

Background: For men and women, taller height is associated with increased risk of all cancers combined. For colorectal cancer (CRC), it is unclear whether the differential association of height by sex is real or is due to confounding or bias inherent in observational studies. We performed a Mendelian randomization study to examine the association between height and CRC risk.

Methods: To minimize confounding and bias, we derived a weighted genetic risk score predicting height (using 696 genetic variants associated with height) in 10,226 CRC cases and 10,286 controls. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for associations between height, genetically predicted height and CRC.

Results: Using conventional methods, increased height (per 10-cm increment) was associated with increased CRC risk (OR = 1.08, 95% CI = 1.02-1.15). In sex-specific analyses, height was associated with CRC risk for women (OR = 1.15, 95% CI = 1.05-1.26), but not men (OR = 0.98, 95% CI = 0.92-1.05). Consistent with these results, carrying greater numbers of (weighted) height-increasing alleles (per 1-unit increase) was associated with higher CRC risk for women and men combined (OR = 1.07, 95% CI = 1.01-1.14) and for women (OR = 1.09, 95% CI = .01-1.19). There was weaker evidence of an association for men (OR = 1.05, 95% CI = 0.96-1.15).

Conclusion: We provide evidence for a causal association between height and CRC for women. The CRC-height association for men remains unclear and warrants further investigation in other large studies.

Keywords: Body height; colorectal cancer; epidemiology.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Body Height / genetics*
Case-Control Studies
Colonic Neoplasms / genetics*
Female
Humans
Male
Mendelian Randomization Analysis
Middle Aged
Rectal Neoplasms / genetics*
Risk Factors
Sex Distribution

Abstract

Publication types

MeSH terms

Grants and funding