The Causal Relevance of Body Mass Index in Different Histological Types of Lung Cancer: A Mendelian Randomization Study

Authors

Robert Carreras-Torres, International Agency for Research on Cancer (IARC)Follow
Philip C. Haycock, University of Bristol
Caroline L. Relton, University of Bristol
Richard M. Martin, University of Bristol
George Davey Smith, University of Bristol
Peter Kraft, Harvard T.H. Chan School of Public Health
Chi Gao, Harvard T.H. Chan School of Public Health,
Shelley Tworoger, Harvard T.H. Chan School of Public Health,
Loic Le Marchand, University of Hawaii Cancer Center
Lynne R. Wilkens, University of Hawaii Cancer Center
Sungshim L. Park, University of Southern California
Christopher Haiman, University of Southern California
John K. Field, The University of LiverpoolFollow
Michael Davies, The University of LiverpoolFollow
Mihcael Marcus, The University of Liverpool
Geoffrey Liu, Ontario Cancer Institute, Princess Margaret Cancer Center
Neil E. Caporaso, DCEG
David C. Christiani, Harvard T. H. Chan School of Public Health
Yongyue Wei, Harvard T. H. Chan School of Public Health
Chu Chen, Fred Hutchinson Cancer Research CenterFollow
Jennifer A. Doherty, Dartmouth CollegeFollow
Gianluca Severi, Human Genetics Foundation (HuGeF)
Gary E. Goodman, Fred Hutchinson Cancer Research CenterFollow
Rayjean J. Hung, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital
Christopher I. I. Amos, Dartmouth CollegeFollow
James McKay, International Agency for Research on Cancer (IARC)
Mattias Johansson, International Agency for Research on Cancer (IARC)
Paul Brennan, International Agency for Research on Cancer (IARC)Follow

Document Type

Article

Publication Date

8-4-2016

Publication Title

Scientific Reports

Department

Geisel School of Medicine

Abstract

Body mass index (BMI) is inversely associated with lung cancer risk in observational studies, even though it increases the risk of several other cancers, which could indicate confounding by tobacco smoking or reverse causality. We used the two-sample Mendelian randomization (MR) approach to circumvent these limitations of observational epidemiology by constructing a genetic instrument for BMI, based on results from the GIANT consortium, which was evaluated in relation to lung cancer risk using GWAS results on 16,572 lung cancer cases and 21,480 controls. Results were stratified by histological subtype, smoking status and sex. An increase of one standard deviation (SD) in BMI (4.65 Kg/m²) raised the risk for lung cancer overall (OR = 1.13; P = 0.10). This was driven by associations with squamous cell (SQ) carcinoma (OR = 1.45; P = 1.2 × 10⁻³) and small cell (SC) carcinoma (OR = 1.81; P = 0.01). An inverse trend was seen for adenocarcinoma (AD) (OR = 0.82; P = 0.06). In stratified analyses, a 1 SD increase in BMI was inversely associated with overall lung cancer in never smokers (OR = 0.50; P = 0.02). These results indicate that higher BMI may increase the risk of certain types of lung cancer, in particular SQ and SC carcinoma.

DOI

10.1038/srep31121

Dartmouth Digital Commons Citation

Carreras-Torres, Robert; Haycock, Philip C.; Relton, Caroline L.; Martin, Richard M.; Smith, George Davey; Kraft, Peter; Gao, Chi; Tworoger, Shelley; Le Marchand, Loic; Wilkens, Lynne R.; Park, Sungshim L.; Haiman, Christopher; Field, John K.; Davies, Michael; Marcus, Mihcael; Liu, Geoffrey; Caporaso, Neil E.; Christiani, David C.; Wei, Yongyue; Chen, Chu; Doherty, Jennifer A.; Severi, Gianluca; Goodman, Gary E.; Hung, Rayjean J.; Amos, Christopher I. I.; McKay, James; Johansson, Mattias; and Brennan, Paul, "The Causal Relevance of Body Mass Index in Different Histological Types of Lung Cancer: A Mendelian Randomization Study" (2016). Dartmouth Scholarship. 3391.
https://digitalcommons.dartmouth.edu/facoa/3391