title: Regular inhaled corticosteroids in adult-onset asthma and the risk for future cancer: a population-based cohort study with proper person-time analysis.
abstract: BACKGROUND
  Recent studies have shown that inhaled corticosteroids (ICS) can exert anti-inflammatory effects for chronic airway diseases, and several observational studies suggest that they play a role as cancer chemopreventive agents, particularly against lung cancer. We aimed to examine whether regular ICS use was associated with a reduced risk for future malignancy in patients with newly diagnosed adult-onset asthma.
  
  
  METHODS
  We used a population-based cohort study between 2001 and 2008 with appropriate person-time analysis. Participants were followed up until the first incident of cancer, death, or to the end of 2008. The Cox model was used to derive an adjusted hazard ratio (aHR) for cancer development. Kaplan-Meier cancer-free survival curves of two groups were compared.
  
  
  RESULTS
  The exposed group of 2,117 regular ICS users and the nonexposed group of 17,732 non-ICS users were assembled. After 7,365 (mean, 3.5 years; standard deviation 2.1) and 73,789 (mean, 4.1 years; standard deviation 2.4) person-years of follow-up for the ICS users and the comparator group of non-ICS users, respectively, the aHR for overall cancer was nonsignificantly elevated at 1.33 with 95% confidence interval (CI), 1.00-1.76, P=0.0501. The Kaplan-Meier curves for overall cancer-free proportions of both groups were not significant (log-rank, P=0.065). Synergistic interaction of concurrent presence of regular ICS use was conducted using "ICS-negative and chronic obstructive pulmonary disease (COPD)-negative" as the reference. The aHR for the group of "ICS-positive, COPD-negative" did not reach statistically significant levels with aHR at 1.38 (95% CI, 0.53-3.56). There was a statistically significant synergistic interaction of concurrent presence of regular ICS use and COPD with aHR at 3.78 (95% CI, 2.10-6.81).
  
  
  CONCLUSIONS
  The protective effect of regular ICS use in the studied East Asian patients with adult-onset asthma was not detectable, contrary to reports of previous studies that ICS might prevent the occurrence of future cancer.
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Kuang Tien General Hospital, Taichung, Taiwan ; Department of Biomedical Informatics, Asia University Taiwan, Taichung, Taiwan.
authors.forename: Victor C
authors.initials: VC
authors.lastname: Kok
authors.affiliation: Department of Biomedical Informatics, Asia University Taiwan, Taichung, Taiwan ; Department of Computer Science and Information Engineering, National Central University, Jhongli, Taiwan.
authors.forename: Jorng-Tzong
authors.initials: JT
authors.lastname: Horng
authors.affiliation: Department of Computer Science and Information Engineering, National Central University, Jhongli, Taiwan.
authors.forename: Hsu-Kai
authors.initials: HK
authors.lastname: Huang
authors.affiliation: Statistics Unit, Department of Applied Geomatics, Chien Hsin University, Jhongli, Taiwan.
authors.forename: Tsung-Ming
authors.initials: TM
authors.lastname: Chao
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan.
authors.forename: Ya-Fang
authors.initials: YF
authors.lastname: Hong
keywords: NHIRD; immortal time bias; population-based study; retrospective cohort study; risk of cancer
references.citation: Am Rev Respir Dis. 1990 Oct;142(4):832-6
references.pmid: 2221590
references.citation: Eur Respir Rev. 2013 Mar 1;22(127):44-52
references.pmid: 23457164
references.citation: PLoS One. 2014 Jun 04;9(6):e99102
references.pmid: 24897240
references.citation: Clin Cancer Res. 2004 Oct 1;10(19):6502-11
references.pmid: 15475437
references.citation: Chest. 2008 Jul;134(1):1-2
references.pmid: 18628211
references.citation: Respirology. 2013 Jul;18(5):840-7
references.pmid: 23617551
references.citation: Int J Chron Obstruct Pulmon Dis. 2014 May 27;9:533-42
references.pmid: 24920891
references.citation: Chest. 2009 Aug;136(2):405-11
references.pmid: 19318663
references.citation: Cancer Res. 1997 Dec 15;57(24):5489-92
references.pmid: 9407956
references.citation: Pharmacoepidemiol Drug Saf. 2007 Jan;16(1):86-95
references.pmid: 17006967
references.citation: Epidemiology. 1992 Sep;3(5):452-6
references.pmid: 1391139
references.citation: Am J Respir Crit Care Med. 2006 Feb 15;173(4):464; author reply 464-5
references.pmid: 16467177
references.citation: Am J Respir Crit Care Med. 2008 Jun 1;177(11):1207-14
references.pmid: 18310480
references.citation: Eur Respir J. 2004 Mar;23(3):391-5
references.pmid: 15065827
references.citation: Pharmacoepidemiol Drug Saf. 2007 Mar;16(3):241-9
references.pmid: 17252614
references.citation: Cancer Prev Res (Phila). 2011 Jan;4(1):34-42
references.pmid: 21163939
references.citation: Am J Respir Crit Care Med. 2003 Jul 1;168(1):49-53
references.pmid: 12663327
references.citation: Am J Respir Crit Care Med. 2007 Apr 1;175(7):712-9
references.pmid: 17185647
references.citation: BMC Cardiovasc Disord. 2012 Nov 21;12:108
references.pmid: 23170782
references.citation: Chest. 2008 Sep;134(3):546-51
references.pmid: 18641096
references.citation: Respir Med. 2013 Aug;107(8):1222-33
references.pmid: 23768737
references.citation: Respir Med. 2011 Nov;105(11):1622-8
references.pmid: 21757331
references.citation: Ann Pharmacother. 2009 Mar;43(3):519-27
references.pmid: 19261959
references.citation: Mediators Inflamm. 1995;4(6):426-30
references.pmid: 18475675
references.citation: Allergy. 2013;68(5):674-80
references.pmid: 23590217
references.citation: BMC Cancer. 2014 Aug 29;14:634
references.pmid: 25174953
references.citation: Ann Am Thorac Soc. 2013 Jun;10(3):188-97
references.pmid: 23802814
references.citation: Respir Med. 2009 Jan;103(1):85-90
references.pmid: 18793832
references.citation: Am J Cardiol. 2011 Sep 15;108(6):902-3
references.pmid: 21884882