Factors associated with lung cancer in COPD patients

Martin Sandelin, Stéphanie Mindus, Marcus Thuresson, Karin Lisspers, Björn Ställberg, Gunnar Johansson, Kjell Larsson, Christer Janson, Martin Sandelin, Stéphanie Mindus, Marcus Thuresson, Karin Lisspers, Björn Ställberg, Gunnar Johansson, Kjell Larsson, Christer Janson

Abstract

Background: The risk of dying of lung cancer is up to eightfold higher in patients with COPD than in age- and gender-matched controls. The aim of this study was to investigate the factors associated with lung cancer in a large cohort of COPD patients from primary care centers.

Methods: To analyze whether age, gender, socioeconomic factors, comorbidity, and medication affect the risk of lung cancer in COPD, we used a COPD cohort of primary care patients. Data from primary care medical records and mandatory Swedish national registers were collected and linked in this population-based, retrospective observational registry study (NCT01146392).

Results: Of the total cohort, 19,894 patients were included in the study. Five hundred and ninety-four lung cancer cases were diagnosed, corresponding to 3.0% of the studied population. In a multivariate analysis, the risk of lung cancer was lower if the COPD patients had a concurrent asthma diagnosis (HR: 0.54, CI: 0.41-0.71), while the risk of lung cancer increased with increasing age. A decreased lung cancer risk was observed in an exposure-dependent manner in patients who were prescribed inhaled corticosteroids (HR: 0.52, CI: 0.37-0.73), while the opposite was found for the use of acetylsalicylic acid (HR: 1.58, CI: 1.15-2.16).

Conclusion: In this large population-based cohort, a concurrent asthma diagnosis and use of inhaled corticosteroids were independently related to decreased risk of lung cancer in COPD patients, while the use of acetylsalicylic acid was associated with an increased risk. The findings of the present study should be seen as hypothesis generating and need to be confirmed in prospective studies.

Keywords: ACO; NSCLC; asthma; inhaled corticosteroids; risk factor.

Conflict of interest statement

Disclosure Martin Sandelin has received honoraria for lectures from AstraZeneca, Novartis, Boehringer Ingelheim, and Amirall and has received grants from the Professor John Naeslunds Stipendiefond, Ture Stenholms Minnesfond and Uppsala County Association Against Heart and Lung Diseases. Karin Lisspers has received honoraria for educational activities and lectures from AstraZeneca, GlaxoSmithKline, Novartis, MEDA, and Takeda and has served on advisory boards arranged by MEDA and Novartis. Kjell Larsson has, during the last 5 years, on one or more occasion served on an advisory board, served as a speaker, and/or participated in education arranged by AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Takeda, Novartis, Chiesi, Orion, and TEVA. Gunnar Johansson has served on advisory boards arranged by Astra Zeneca, Novo Nordisk, and Takeda. Christer Janson has received honoraria for educational activities and lectures from Novartis, AstraZeneca, GlaxoSmithKline, and Boehringer Ingelheim outside the submitted work. Björn Ställberg has received honoraria for educational activities and lectures from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, MEDA, and TEVA and has served on advisory boards arranged by AstraZeneca, Novartis, GSK, Boehringer Ingelheim, TEVA, and MEDA. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
The independent association between the relative exposure (calculated as the proportion of days covered of the drug, during the study period) of inhaled corticosteroids and the risk of developing lung cancer assessed by step wise Cox regression in relation to having or not having concurrent asthma.

References

    1. Teramoto S. 1. COPD pathogenesis from the viewpoint of risk factors. Intern Med. 2007;46(2):77–79.
    1. Sorheim IC, Johannessen A, Gulsvik A, et al. Gender differences in COPD: are women more susceptible to smoking effects than men? Thorax. 2010;65(6):480–485.
    1. Houghton AM. Mechanistic links between COPD and lung cancer. Nat Rev Cancer. 2013;13(4):233–245.
    1. Stallberg B, Janson C, Johansson G, et al. Management, morbidity and mortality of COPD during an 11-year period: an observational retrospective epidemiological register study in Sweden (PATHOS) Prim Care Respir J. 2014;23(1):38–45.
    1. Mannino DM, Aguayo SM, Petty TL, Redd SC. Low lung function and incident lung cancer in the United States: data From the First National Health and Nutrition Examination Survey follow-up. Arch Intern Med. 2003;163(12):1475–1480.
    1. Church DF, Pryor WA. Free-radical chemistry of cigarette smoke and its toxicological implications. Environ Health Perspect. 1985;64:111–126.
    1. Goldkorn T, Filosto S, Chung S. Lung injury and lung cancer caused by cigarette smoke-induced oxidative stress: Molecular mechanisms and therapeutic opportunities involving the ceramide-generating machinery and epidermal growth factor receptor. Antioxid Redox Signal. 2014;21(15):2149–2174.
    1. Turner MC, Chen Y, Krewski D, Calle EE, Thun MJ. Chronic obstructive pulmonary disease is associated with lung cancer mortality in a prospective study of never smokers. Am J Respir Crit Care Med. 2007;176(3):285–290.
    1. Brenner DR, Boffetta P, Duell EJ, et al. Previous lung diseases and lung cancer risk: a pooled analysis from the International Lung Cancer Consortium. Am J Epidemiol. 2012;176(7):573–585.
    1. de Torres JP, Bastarrika G, Wisnivesky JP, et al. Assessing the relationship between lung cancer risk and emphysema detected on low-dose CT of the chest. Chest. 2007;132(6):1932–1938.
    1. Parimon T, Chien JW, Bryson CL, et al. Inhaled corticosteroids and risk of lung cancer among patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007;175(7):712–719.
    1. Lee CH, Hyun MK, Jang EJ, et al. Inhaled corticosteroid use and risks of lung cancer and laryngeal cancer. Respir Med. 2013;107(8):1222–1233.
    1. Sayin VI, Ibrahim MX, Larsson E, et al. Antioxidants accelerate lung cancer progression in mice. Sci Transl Med. 2014;6(221):221r.a15.
    1. Jiang HY, Huang TB, Xu L, et al. Aspirin use and lung cancer risk: a possible relationship? Evidence from an updated meta-analysis. PLoS One. 2015;10(4):e0122962.
    1. Lisspers K, Johansson G, Jansson C, et al. Improvement in COPD management by access to asthma/COPD clinics in primary care: data from the observational PATHOS study. Respir Med. 2014;108(9):1345–1354.
    1. Soler-Cataluna JJ, Cosio B, Izquierdo JL, et al. Consensus document on the overlap phenotype COPD-asthma in COPD. Archiv Bronconeumol. 2012;48(9):331–337.
    1. Chatila WM, Thomashow BM, Minai OA, Criner GJ, Make BJ. Comorbidities in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2008;5(4):549–555.
    1. Vanfleteren LE, Spruit MA, Groenen M, et al. Clusters of comorbidities based on validated objective measurements and systemic inflammation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;187(7):728–735.
    1. Zhang MW, Ho RC, Cheung MW, Fu E, Mak A. Prevalence of depressive symptoms in patients with chronic obstructive pulmonary disease: a systematic review, meta-analysis and meta-regression. Gen Hosp Psychiatry. 2011;33(3):217–223.
    1. Martinell M, Stalhammar J, Hallqvist J. Automated data extraction – a feasible way to construct patient registers of primary care utilization. Ups J Med Sci. 2012;117(1):52–56.
    1. Santillan AA, Camargo CA, Jr, Colditz GA. A meta-analysis of asthma and risk of lung cancer (United States) Cancer Causes Control. 2003;14(4):327–334.
    1. Gorlova OY, Zhang Y, Schabath MB, et al. Never smokers and lung cancer risk: a case-control study of epidemiological factors. Int J Cancer. 2006;118(7):1798–1804.
    1. El-Zein M, Parent ME, Ka K, et al. History of asthma or eczema and cancer risk among men: a population-based case-control study in Montreal, Quebec, Canada. Ann Allergy Asthma Immunol. 2010;104(5):378–384.
    1. Ramanakumar AV, Parent ME, Menzies D, Siemiatycki J. Risk of lung cancer following nonmalignant respiratory conditions: evidence from two case-control studies in Montreal, Canada. Lung Cancer. 2006;53(1):5–12.
    1. Harada T, Yamasaki A, Fukushima T, et al. Causes of death in patients with asthma and asthma-chronic obstructive pulmonary disease overlap syndrome. Int J Chron Obstruct Pulm Dis. 2015;10:595–602.
    1. Sohal SS, Soltani A, Reid D, et al. A randomized controlled trial of inhaled corticosteroids (ICS) on markers of epithelial-mesenchymal transition (EMT) in large airway samples in COPD: an exploratory proof of concept study. Int J Chron Obstruct Pulm Dis. 2014;9:533–542.
    1. Jacobs EJ, Thun MJ, Bain EB, et al. A large cohort study of long-term daily use of adult-strength aspirin and cancer incidence. J Natl Cancer Inst. 2007;99(8):608–615.
    1. Ishikawa H, Wakabayashi K, Suzuki S, et al. Preventive effects of low-dose aspirin on colorectal adenoma growth in patients with familial adenomatous polyposis: double-blind, randomized clinical trial. Cancer Med. 2013;2(1):50–56.
    1. Ye X, Fu J, Yang Y, et al. Frequency-risk and duration-risk relationships between aspirin use and gastric cancer: a systematic review and meta-analysis. PLoS One. 2013;8(7):e71522.
    1. Khuder SA, Herial NA, Mutgi AB, Federman DJ. Nonsteroidal anti-inflammatory drug use and lung cancer: a metaanalysis. Chest. 2005;127(3):748–754.
    1. McCormack VA, Hung RJ, Brenner DR, et al. Aspirin and NSAID use and lung cancer risk: a pooled analysis in the International Lung Cancer Consortium (ILCCO) Cancer Causes Control. 2011;22(12):1709–1720.
    1. Lim WY, Chuah KL, Eng P, et al. Aspirin and non-aspirin non-steroidal anti-inflammatory drug use and risk of lung cancer. Lung Cancer. 2012;77(2):246–251.
    1. Feskanich D, Bain C, Chan AT, et al. Aspirin and lung cancer risk in a cohort study of women: dosage, duration and latency. Br J Cancer. 2007;97(9):1295–1299.
    1. Hernandez-Diaz S, Garcia Rodriguez LA. Nonsteroidal anti-inflammatory drugs and risk of lung cancer. Int J Cancer. 2007;120(7):1565–1572.
    1. Meyer A, Buhl R, Magnussen H. The effect of oral N-acetylcysteine on lung glutathione levels in idiopathic pulmonary fibrosis. Eur Respir J. 1994;7(3):431–436.
    1. Celli B, Decramer M, Kesten S, et al. Mortality in the 4-year trial of tiotropium (UPLIFT) in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2009;180(10):948–955.
    1. Zhong S, Zhang X, Chen L, et al. Statin use and mortality in cancer patients: systematic review and meta-analysis of observational studies. Cancer Treat Rev. 2015;41(6):554–567.

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться