BACKGROUND: Identifying circulating metabolites related to cigarette smoking may provide insight into the biological mechanisms of smoking-related diseases and the nature of addiction. However, previous studies are limited, generally small, and have largely targeted a priori metabolites. METHODS: We examined associations between cigarette smoking and metabolites using an untargeted metabolomics approach in 892 men and women from four studies including participants from Italy, USA, China and Finland. We examined associations between individual log-transformed metabolites and two key smoking phenotypes (current smoking status and cigarettes per day [cig/day]) using linear regression. Fixed-effect meta-analysis was used to combine results across studies. Strict Bonferroni thresholds were used as our significance criteria. We further examined associated metabolites with other metrics of smoking behaviuor (current versus former, former versus never, smoking duration and years since quitting) in the US study. RESULTS: We identified a total of 25 metabolites associated with smoking behaviours; 24 were associated with current smoking status and eight with cig/day. In addition to three well-established nicotine metabolites (cotinine, hydroxycotinine, cotinine N-oxide), we found an additional 12 xenobiotic metabolites involved in benzoatic (e.g. 3-ethylphenylsulphate) or xanthine metabolism (e.g. 1-methylurate), three amino acids (o-cresol sulphate, serotonin, indolepropionate), two lipids (scyllo-inositol, pregnenolone sulphate), four vitamins or cofactors [e.g. bilirubin (Z,Z)], and one carbohydrate (oxalate). CONCLUSIONS: We identified associations between cigarette smoking and a diverse range of metabolites. Our findings, with further validation in future studies, have implications regarding aetiology and study design of smoking-related diseases. Published by Oxford University Press on behalf of the International Epidemiological Association 2015. This work is written by US Government employees and is in the public domain in the United States.
BACKGROUND: Identifying circulating metabolites related to cigarette smoking may provide insight into the biological mechanisms of smoking-related diseases and the nature of addiction. However, previous studies are limited, generally small, and have largely targeted a priori metabolites. METHODS: We examined associations between cigarette smoking and metabolites using an untargeted metabolomics approach in 892 men and women from four studies including participants from Italy, USA, China and Finland. We examined associations between individual log-transformed metabolites and two key smoking phenotypes (current smoking status and cigarettes per day [cig/day]) using linear regression. Fixed-effect meta-analysis was used to combine results across studies. Strict Bonferroni thresholds were used as our significance criteria. We further examined associated metabolites with other metrics of smoking behaviuor (current versus former, former versus never, smoking duration and years since quitting) in the US study. RESULTS: We identified a total of 25 metabolites associated with smoking behaviours; 24 were associated with current smoking status and eight with cig/day. In addition to three well-established nicotine metabolites (cotinine, hydroxycotinine, cotinine N-oxide), we found an additional 12 xenobiotic metabolites involved in benzoatic (e.g. 3-ethylphenylsulphate) or xanthine metabolism (e.g. 1-methylurate), three amino acids (o-cresol sulphate, serotonin, indolepropionate), two lipids (scyllo-inositol, pregnenolone sulphate), four vitamins or cofactors [e.g. bilirubin (Z,Z)], and one carbohydrate (oxalate). CONCLUSIONS: We identified associations between cigarette smoking and a diverse range of metabolites. Our findings, with further validation in future studies, have implications regarding aetiology and study design of smoking-related diseases. Published by Oxford University Press on behalf of the International Epidemiological Association 2015. This work is written by US Government employees and is in the public domain in the United States.
Authors: Daniel C Müller; Christian Degen; Gerhard Scherer; Gerhard Jahreis; Reinhard Niessner; Max Scherer Journal: J Chromatogr B Analyt Technol Biomed Life Sci Date: 2014-03-03 Impact factor: 3.205
Authors: Arun Sreekumar; Laila M Poisson; Thekkelnaycke M Rajendiran; Amjad P Khan; Qi Cao; Jindan Yu; Bharathi Laxman; Rohit Mehra; Robert J Lonigro; Yong Li; Mukesh K Nyati; Aarif Ahsan; Shanker Kalyana-Sundaram; Bo Han; Xuhong Cao; Jaeman Byun; Gilbert S Omenn; Debashis Ghosh; Subramaniam Pennathur; Danny C Alexander; Alvin Berger; Jeffrey R Shuster; John T Wei; Sooryanarayana Varambally; Christopher Beecher; Arul M Chinnaiyan Journal: Nature Date: 2009-02-12 Impact factor: 49.962
Authors: Amanda J Cross; Simina Boca; Neal D Freedman; Neil E Caporaso; Wen-Yi Huang; Rashmi Sinha; Joshua N Sampson; Steven C Moore Journal: Carcinogenesis Date: 2014-03-19 Impact factor: 4.944
Authors: Rui Wang-Sattler; Yao Yu; Kirstin Mittelstrass; Eva Lattka; Elisabeth Altmaier; Christian Gieger; Karl H Ladwig; Norbert Dahmen; Klaus M Weinberger; Pei Hao; Lei Liu; Yixue Li; H-Erich Wichmann; Jerzy Adamski; Karsten Suhre; Thomas Illig Journal: PLoS One Date: 2008-12-05 Impact factor: 3.240
Authors: Qi Yan; Zeyan Liew; Karan Uppal; Xin Cui; Chenxiao Ling; Julia E Heck; Ondine S von Ehrenstein; Jun Wu; Douglas I Walker; Dean P Jones; Beate Ritz Journal: Environ Int Date: 2019-06-20 Impact factor: 9.621
Authors: Lukas Entenmann; Maik Pietzner; Anna Artati; Anke Hannemann; Ann-Kristin Henning; Gabi Kastenmüller; Henry Völzke; Matthias Nauck; Jerzy Adamski; Henri Wallaschofski; Nele Friedrich Journal: PLoS One Date: 2017-09-18 Impact factor: 3.240
Authors: Atif Khan; Thomas H Thatcher; Collynn F Woeller; Patricia J Sime; Richard P Phipps; Philip K Hopke; Mark J Utell; Pamela L Krahl; Timothy M Mallon; Juilee Thakar Journal: J Occup Environ Med Date: 2019-12 Impact factor: 2.162
Authors: Elizabeth A Regan; Craig P Hersh; Peter J Castaldi; Dawn L DeMeo; Edwin K Silverman; James D Crapo; Russell P Bowler Journal: Am J Respir Cell Mol Biol Date: 2019-08 Impact factor: 6.914
Authors: Peter G Shields; Micah Berman; Theodore M Brasky; Jo L Freudenheim; Ewy Mathe; Joseph P McElroy; Min-Ae Song; Mark D Wewers Journal: Cancer Epidemiol Biomarkers Prev Date: 2017-06-22 Impact factor: 4.254
Authors: Jiaqi Huang; Stephanie J Weinstein; Steven C Moore; Andriy Derkach; Xing Hua; Linda M Liao; Fangyi Gu; Alison M Mondul; Joshua N Sampson; Demetrius Albanes Journal: Am J Epidemiol Date: 2018-08-01 Impact factor: 4.897
Authors: Sophia Kwon; Myeonggyun Lee; George Crowley; Theresa Schwartz; Rachel Zeig-Owens; David J Prezant; Mengling Liu; Anna Nolan Journal: Am J Respir Crit Care Med Date: 2021-11-01 Impact factor: 21.405
Authors: Hana Zahed; Mattias Johansson; Per M Ueland; Øivind Midttun; Roger L Milne; Graham G Giles; Jonas Manjer; Malte Sandsveden; Arnulf Langhammer; Elin Pettersen Sørgjerd; Kjell Grankvist; Mikael Johansson; Neal D Freedman; Wen-Yi Huang; Chu Chen; Ross Prentice; Victoria L Stevens; Ying Wang; Loic Le Marchand; Lynne R Wilkens; Stephanie J Weinstein; Demetrius Albanes; Qiuyin Cai; William J Blot; Alan A Arslan; Anne Zeleniuch-Jacquotte; Xiao-Ou Shu; Wei Zheng; Jian-Min Yuan; Woon-Puay Koh; Kala Visvanathan; Howard D Sesso; Xuehong Zhang; J Michael Gaziano; Anouar Fanidi; David Muller; Paul Brennan; Florence Guida; Hilary A Robbins Journal: Sci Rep Date: 2021-07-05 Impact factor: 4.996