Obesity, metabolic factors and risk of different histological types of lung cancer: A Mendelian randomization study
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Obesity, metabolic factors and risk of different histological types of lung cancer : A Mendelian randomization study. / Carreras-Torres, Robert; Johansson, Mattias; Haycock, Philip C; Wade, Kaitlin H; Relton, Caroline L; Martin, Richard M; Davey Smith, George; Albanes, Demetrius; Aldrich, Melinda C; Andrew, Angeline; Arnold, Susanne M; Bickeböller, Heike; Bojesen, Stig E; Brunnström, Hans; Manjer, Jonas; Brüske, Irene; Caporaso, Neil E; Chen, Chu; Christiani, David C; Christian, W Jay; Doherty, Jennifer A; Duell, Eric J; Field, John K; Davies, Michael P A; Marcus, Michael W; Goodman, Gary E; Grankvist, Kjell; Haugen, Aage; Hong, Yun-Chul; Kiemeney, Lambertus A; van der Heijden, Erik H F M; Kraft, Peter; Johansson, Mikael B; Lam, Stephen; Landi, Maria Teresa; Lazarus, Philip; Le Marchand, Loïc; Liu, Geoffrey; Melander, Olle; Park, Sungshim L; Rennert, Gad; Risch, Angela; Haura, Eric B; Scelo, Ghislaine; Zaridze, David; Mukeriya, Anush; Savić, Milan; Lissowska, Jolanta; Swiatkowska, Beata; Janout, Vladimir; Holcatova, Ivana; Mates, Dana; Schabath, Matthew B; Shen, Hongbing; Tardon, Adonina; Teare, M Dawn; Woll, Penella; Tsao, Ming-Sound; Wu, Xifeng; Yuan, Jian-Min; Hung, Rayjean J; Amos, Christopher I; McKay, James; Brennan, Paul.
I: PloS one, Bind 12, Nr. 6, e0177875, 2017.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Obesity, metabolic factors and risk of different histological types of lung cancer
T2 - A Mendelian randomization study
AU - Carreras-Torres, Robert
AU - Johansson, Mattias
AU - Haycock, Philip C
AU - Wade, Kaitlin H
AU - Relton, Caroline L
AU - Martin, Richard M
AU - Davey Smith, George
AU - Albanes, Demetrius
AU - Aldrich, Melinda C
AU - Andrew, Angeline
AU - Arnold, Susanne M
AU - Bickeböller, Heike
AU - Bojesen, Stig E
AU - Brunnström, Hans
AU - Manjer, Jonas
AU - Brüske, Irene
AU - Caporaso, Neil E
AU - Chen, Chu
AU - Christiani, David C
AU - Christian, W Jay
AU - Doherty, Jennifer A
AU - Duell, Eric J
AU - Field, John K
AU - Davies, Michael P A
AU - Marcus, Michael W
AU - Goodman, Gary E
AU - Grankvist, Kjell
AU - Haugen, Aage
AU - Hong, Yun-Chul
AU - Kiemeney, Lambertus A
AU - van der Heijden, Erik H F M
AU - Kraft, Peter
AU - Johansson, Mikael B
AU - Lam, Stephen
AU - Landi, Maria Teresa
AU - Lazarus, Philip
AU - Le Marchand, Loïc
AU - Liu, Geoffrey
AU - Melander, Olle
AU - Park, Sungshim L
AU - Rennert, Gad
AU - Risch, Angela
AU - Haura, Eric B
AU - Scelo, Ghislaine
AU - Zaridze, David
AU - Mukeriya, Anush
AU - Savić, Milan
AU - Lissowska, Jolanta
AU - Swiatkowska, Beata
AU - Janout, Vladimir
AU - Holcatova, Ivana
AU - Mates, Dana
AU - Schabath, Matthew B
AU - Shen, Hongbing
AU - Tardon, Adonina
AU - Teare, M Dawn
AU - Woll, Penella
AU - Tsao, Ming-Sound
AU - Wu, Xifeng
AU - Yuan, Jian-Min
AU - Hung, Rayjean J
AU - Amos, Christopher I
AU - McKay, James
AU - Brennan, Paul
PY - 2017
Y1 - 2017
N2 - BACKGROUND: Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer.METHODS AND FINDINGS: We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR) [95% confidence interval (CI)] = 1.20 [1.01-1.43] and for small cell lung cancer (OR [95%CI] = 1.52 [1.15-2.00]) for each standard deviation (SD) increase in BMI [4.6 kg/m2]), but not for adenocarcinoma (OR [95%CI] = 0.93 [0.79-1.08]) (Pheterogeneity = 4.3x10-3). Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10-3), providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95%CI] = 0.90 [0.84-0.97] per SD of 38 mg/dl), while fasting insulin was positively associated (OR [95%CI] = 1.63 [1.25-2.13] per SD of 44.4 pmol/l). Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results.CONCLUSIONS: Our results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously unrecognized effect of obesity on smoking behavior.
AB - BACKGROUND: Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer.METHODS AND FINDINGS: We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR) [95% confidence interval (CI)] = 1.20 [1.01-1.43] and for small cell lung cancer (OR [95%CI] = 1.52 [1.15-2.00]) for each standard deviation (SD) increase in BMI [4.6 kg/m2]), but not for adenocarcinoma (OR [95%CI] = 0.93 [0.79-1.08]) (Pheterogeneity = 4.3x10-3). Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10-3), providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95%CI] = 0.90 [0.84-0.97] per SD of 38 mg/dl), while fasting insulin was positively associated (OR [95%CI] = 1.63 [1.25-2.13] per SD of 44.4 pmol/l). Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results.CONCLUSIONS: Our results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously unrecognized effect of obesity on smoking behavior.
KW - Body Mass Index
KW - Fasting
KW - Humans
KW - Insulin
KW - Insulin Resistance
KW - Likelihood Functions
KW - Lipids
KW - Lung Neoplasms
KW - Mendelian Randomization Analysis
KW - Obesity
KW - Phenotype
KW - Polymorphism, Single Nucleotide
KW - Risk Factors
KW - Journal Article
U2 - 10.1371/journal.pone.0177875
DO - 10.1371/journal.pone.0177875
M3 - Journal article
C2 - 28594918
VL - 12
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 6
M1 - e0177875
ER -
ID: 186482477