Danxia Yu1, Wei Zheng1, Mattias Johansson2, Qing Lan3, Yikyung Park4, Emily White5, Charles E Matthews3, Norie Sawada6, Yu-Tang Gao7, Kim Robien8, Rashmi Sinha3, Arnulf Langhammer9, Rudolf Kaaks10,11, Edward L Giovannucci12,13, Linda M Liao3, Yong-Bing Xiang7, DeAnn Lazovich14, Ulrike Peters5, Xuehong Zhang13, Bas Bueno-de-Mesquita15,16,17,18, Walter C Willett12,13, Shoichiro Tsugane6, Yumie Takata1,19, Stephanie A Smith-Warner12, William Blot1, Xiao-Ou Shu1. 1. Vanderbilt Epidemiology Center, Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN. 2. Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France. 3. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD. 4. Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO. 5. Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA. 6. Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan. 7. State Key Laboratory of Oncogene and Related Genes and Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. 8. Department of Exercise and Nutrition Sciences, Milken Institute School of Public Health, George Washington University, Washington, DC. 9. Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway. 10. Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany. 11. Translational Lung Research Center Heidelberg, Member of the German Center for Lung Research, Heidelberg, Germany. 12. Departments of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA. 13. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. 14. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN. 15. Department for Determinants of Chronic Diseases, National Institute for Public Health and the Environment, Bilthoven, the Netherlands. 16. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands. 17. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. 18. Department of Social and Preventive Medicine, University of Malaya, Kuala Lumpur, Malaysia. 19. College of Public Health and Human Sciences, Oregon State University, Corvallis, OR.
Abstract
Background: The obesity-lung cancer association remains controversial. Concerns over confounding by smoking and reverse causation persist. The influence of obesity type and effect modifications by race/ethnicity and tumor histology are largely unexplored. Methods: We examined associations of body mass index (BMI), waist circumference (WC), and waist-hip ratio (WHR) with lung cancer risk among 1.6 million Americans, Europeans, and Asians. Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for potential confounders. Analyses for WC/WHR were further adjusted for BMI. The joint effect of BMI and WC/WHR was also evaluated. Results: During an average 12-year follow-up, 23 732 incident lung cancer cases were identified. While BMI was generally associated with a decreased risk, WC and WHR were associated with increased risk after controlling for BMI. These associations were seen 10 years before diagnosis in smokers and never smokers, were strongest among blacks, and varied by histological type. After excluding the first five years of follow-up, hazard ratios per 5 kg/m2 increase in BMI were 0.95 (95% CI = 0.90 to 1.00), 0.92 (95% CI = 0.89 to 0.95), and 0.89 (95% CI = 0.86 to 0.91) in never, former, and current smokers, and 0.86 (95% CI = 0.84 to 0.89), 0.94 (95% CI = 0.90 to 0.99), and 1.09 (95% CI = 1.03 to 1.15) for adenocarcinoma, squamous cell, and small cell carcinoma, respectively. Hazard ratios per 10 cm increase in WC were 1.09 (95% CI = 1.00 to 1.18), 1.12 (95% CI = 1.07 to 1.17), and 1.11 (95% CI = 1.07 to 1.16) in never, former, and current smokers, and 1.06 (95% CI = 1.01 to 1.12), 1.20 (95% CI = 1.12 to 1.29), and 1.13 (95% CI = 1.04 to 1.23) for adenocarcinoma, squamous cell, and small cell carcinoma, respectively. Participants with BMIs of less than 25 kg/m2 but high WC had a 40% higher risk (HR = 1.40, 95% CI = 1.26 to 1.56) than those with BMIs of 25 kg/m2 or greater but normal/moderate WC. Conclusions: The inverse BMI-lung cancer association is not entirely due to smoking and reverse causation. Central obesity, particularly concurrent with low BMI, may help identify high-risk populations for lung cancer.
Background: The obesity-lung cancer association remains controversial. Concerns over confounding by smoking and reverse causation persist. The influence of obesity type and effect modifications by race/ethnicity and tumor histology are largely unexplored. Methods: We examined associations of body mass index (BMI), waist circumference (WC), and waist-hip ratio (WHR) with lung cancer risk among 1.6 million Americans, Europeans, and Asians. Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for potential confounders. Analyses for WC/WHR were further adjusted for BMI. The joint effect of BMI and WC/WHR was also evaluated. Results: During an average 12-year follow-up, 23 732 incident lung cancer cases were identified. While BMI was generally associated with a decreased risk, WC and WHR were associated with increased risk after controlling for BMI. These associations were seen 10 years before diagnosis in smokers and never smokers, were strongest among blacks, and varied by histological type. After excluding the first five years of follow-up, hazard ratios per 5 kg/m2 increase in BMI were 0.95 (95% CI = 0.90 to 1.00), 0.92 (95% CI = 0.89 to 0.95), and 0.89 (95% CI = 0.86 to 0.91) in never, former, and current smokers, and 0.86 (95% CI = 0.84 to 0.89), 0.94 (95% CI = 0.90 to 0.99), and 1.09 (95% CI = 1.03 to 1.15) for adenocarcinoma, squamous cell, and small cell carcinoma, respectively. Hazard ratios per 10 cm increase in WC were 1.09 (95% CI = 1.00 to 1.18), 1.12 (95% CI = 1.07 to 1.17), and 1.11 (95% CI = 1.07 to 1.16) in never, former, and current smokers, and 1.06 (95% CI = 1.01 to 1.12), 1.20 (95% CI = 1.12 to 1.29), and 1.13 (95% CI = 1.04 to 1.23) for adenocarcinoma, squamous cell, and small cell carcinoma, respectively. Participants with BMIs of less than 25 kg/m2 but high WC had a 40% higher risk (HR = 1.40, 95% CI = 1.26 to 1.56) than those with BMIs of 25 kg/m2 or greater but normal/moderate WC. Conclusions: The inverse BMI-lung cancer association is not entirely due to smoking and reverse causation. Central obesity, particularly concurrent with low BMI, may help identify high-risk populations for lung cancer.
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