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Sci Rep. 2016 Aug 4;6:31121. doi: 10.1038/srep31121.

The causal relevance of body mass index in different histological types of lung cancer: A Mendelian randomization study.

Author information

1
Section of Genetics, International Agency for Research on Cancer (IARC), Lyon, France.
2
MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
3
National Institute for Health Research Biomedical Research Unit in Nutrition, Diet and Lifestyle at University Hospitals Bristol NHS Foundation Trust and the University of Bristol, BS2 8AE, Bristol, UK.
4
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA.
5
Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, USA.
6
Epidemiology Program, University of Hawaii Cancer Center, Honolulu, USA.
7
Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
8
Roy Castle Lung Cancer Research Programme, The University of Liverpool Cancer Research Centre, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, The University of Liverpool, Liverpool, UK.
9
Ontario Cancer Institute, Princess Margaret Cancer Center, Toronto, ON, Canada.
10
Genetic Epidemiology Branch, DCEG, National Cancer Institute, NIH, Rockville, USA.
11
Departments of Environmental Health and Epidemiology, Harvard T. H. Chan School of Public Health and Department of Medicine, Massachusetts General Hospital/Harvard Medical School, Boston, USA.
12
Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA.
13
Department of Epidemiology, Geisel School of Medicine, Dartmouth College, Lebanon, USA.
14
Human Genetics Foundation (HuGeF), Torino, Italy.
15
Fred Hutchinson Cancer Research Center, Seattle, USA.
16
Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Canada.
17
Department of Biomedical Data Science, Geisel School of medicine, Dartmouth College, Lebanon, USA.

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/m(2)) 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.

PMID:
27487993
PMCID:
PMC4973233
DOI:
10.1038/srep31121
[Indexed for MEDLINE]
Free PMC Article

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