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

Robert Carreras-Torres, Philip C Haycock, Caroline L Relton, Richard M Martin, George Davey Smith, Peter Kraft, Chi Gao, Shelley Tworoger, Loïc Le Marchand, Lynne R Wilkens, Sungshim L Park, Christopher Haiman, John K Field, M Davies, Michael Marcus, Geoffrey Liu, Neil E Caporaso, David C Christiani, Yongyue Wei, Chu ChenJennifer A Doherty, Gianluca Severi, Gary E Goodman, Rayjean J Hung, Christopher I Amos, James McKay, Mattias Johansson, Paul Brennan

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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.

Original languageEnglish
Article number31121
Number of pages6
JournalScientific Reports
Publication statusPublished - 4 Aug 2016

Structured keywords

  • ICEP


  • Cancer genomics
  • Epidemiology
  • Lung cancer
  • Risk factors


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