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Randomized Controlled Trial
. 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

Robert Carreras-Torres  1 , Philip C Haycock  2 , Caroline L Relton  2 , Richard M Martin  2   3 , George Davey Smith  2 , Peter Kraft  4 , Chi Gao  4 , Shelley Tworoger  4   5 , Loïc Le Marchand  6 , Lynne R Wilkens  6 , Sungshim L Park  7 , Christopher Haiman  7 , John K Field  8 , Michael Davies  8 , Michael Marcus  8 , Geoffrey Liu  9 , Neil E Caporaso  10 , David C Christiani  11 , Yongyue Wei  11 , Chu Chen  12 , Jennifer A Doherty  13 , Gianluca Severi  14 , Gary E Goodman  15 , Rayjean J Hung  16 , Christopher I Amos  17 , James McKay  1 , Mattias Johansson  1 , Paul Brennan  1
Affiliations
Randomized Controlled Trial

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

Robert Carreras-Torres et al. Sci Rep. .

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.

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Figures

Figure 1
Figure 1. Forest plot of association analyses between genetic BMI score and measured BMI, pack years, and cigarettes per day (CPD) in the whole sample and within cases and controls.
Cotinine levels are shown in Supplementary Table S6. 95%CI: 95% Confidence Interval; P: P value. I2: Heterogeneity coefficient.
Figure 2
Figure 2. Forest plot of lung cancer risk for an increase of 1 SD of BMI (approximately 4.65 Kg/m2) observed in a likelihood-based MR approach.
AD: Adenocarcinoma; SQ: squamous cell lung cancer; SC: small cell lung cancer; OR: Odds Ratio; 95%CI: 95% Confidence Interval; P: P value; P Het: P value of heterogeneity among individual SNP causal estimates.
See this image and copyright information in PMC

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