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; Michael Davies; Michael Marcus; Geoffrey Liu; Neil E. Caporaso; David C. Christiani; Yongyue Wei; Chu Chen; Jennifer A. Doherty; Gianluca Severi; Gary E. Goodman; Rayjean J. Hung; Christopher I. Amos; James McKay; Mattias Johansson; Paul Brennan

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, 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, Michael 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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Résumé

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.

langue originale	Anglais
Numéro d'article	31121
journal	Scientific Reports
Volume	6
Les DOIs	https://doi.org/10.1038/srep31121
état	Publié - 4 août 2016
Modification externe	Oui

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10.1038/srep31121

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Carreras-Torres, R., Haycock, P. C., Relton, C. L., Martin, R. M., Smith, G. D., Kraft, P., Gao, C., Tworoger, S., Le Marchand, L., Wilkens, L. R., Park, S. L., Haiman, C., Field, J. K., Davies, M., Marcus, M., Liu, G., Caporaso, N. E., Christiani, D. C., Wei, Y., ... Brennan, P. (2016). The causal relevance of body mass index in different histological types of lung cancer: A Mendelian randomization study. Scientific Reports, 6, Article 31121. https://doi.org/10.1038/srep31121

@article{b27a66382cd2493a971bc43873e33e4b,

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

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.",

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

year = "2016",

month = aug,

day = "4",

doi = "10.1038/srep31121",

language = "English",

volume = "6",

journal = "Scientific Reports",

issn = "2045-2322",

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Carreras-Torres, R, Haycock, PC, Relton, CL, Martin, RM, Smith, GD, Kraft, P, Gao, C, Tworoger, S, Le Marchand, L, Wilkens, LR, Park, SL, Haiman, C, Field, JK, Davies, M, Marcus, M, Liu, G, Caporaso, NE, Christiani, DC, Wei, Y, Chen, C, Doherty, JA, Severi, G, Goodman, GE, Hung, RJ, Amos, CI, McKay, J, Johansson, M & Brennan, P 2016, 'The causal relevance of body mass index in different histological types of lung cancer: A Mendelian randomization study', Scientific Reports, VOL. 6, 31121. https://doi.org/10.1038/srep31121

TY - JOUR

T1 - The causal relevance of body mass index in different histological types of lung cancer

T2 - A Mendelian randomization study

AU - Carreras-Torres, Robert

AU - Haycock, Philip C.

AU - Relton, Caroline L.

AU - Martin, Richard M.

AU - Smith, George Davey

AU - Kraft, Peter

AU - Gao, Chi

AU - Tworoger, Shelley

AU - Le Marchand, Loïc

AU - Wilkens, Lynne R.

AU - Park, Sungshim L.

AU - Haiman, Christopher

AU - Field, John K.

AU - Davies, Michael

AU - Marcus, Michael

AU - Liu, Geoffrey

AU - Caporaso, Neil E.

AU - Christiani, David C.

AU - Wei, Yongyue

AU - Chen, Chu

AU - Doherty, Jennifer A.

AU - Severi, Gianluca

AU - Goodman, Gary E.

AU - Hung, Rayjean J.

AU - Amos, Christopher I.

AU - McKay, James

AU - Johansson, Mattias

AU - Brennan, Paul

PY - 2016/8/4

Y1 - 2016/8/4

N2 - 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.

AB - 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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U2 - 10.1038/srep31121

DO - 10.1038/srep31121

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VL - 6

JO - Scientific Reports

JF - Scientific Reports

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