Inhaled corticosteroid use and risks of lung cancer and laryngeal cancer

Lee, Chang Hoon; Hyun, Min Kyung; Jang, Eun Jin; Lee, Na Rae; Kim, Kyungjoo; Yim, Jae Joon

doi:10.1016/j.rmed.2012.12.002

Cited by 45 publications

(56 citation statements)

References 43 publications

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“…CR markedly increases corticosterone levels and, importantly, adrenalectomy abolishes the inhibitory effect of CR on skin and lung tumors, but not mammary tumors . Recently, it was reported that the use of inhaled corticosteroid is associated with a dose‐dependent reduced risk of lung cancer in humans . CR inhibition of mammary tumors is more associated with decreased IGF‐1 levels than circulating corticosterone .…”

Section: Discussionmentioning

confidence: 99%

Cancer prevention by adult‐onset calorie restriction after infant exposure to ionizing radiation in B6C3F1 male mice

Shang¹,

Kakinuma²,

Yamauchi

et al. 2014

Intl Journal of Cancer

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Children are especially sensitive to ionizing radiation and chemical carcinogens, and limiting their cancer risk is of great public concern. Calorie restriction (CR) is a potent intervention for suppressing cancer. However, CR is generally not appropriate for children. This study, therefore, examined to see if adult-onset CR influences the lifetime cancer risk in mice after early-life exposure to ionizing radiation. Infant male mice (1-week-old) were exposed to 3.8 Gy X-rays, fed a control 95 kcal/week or CR 65 kcal/week diet from 7 weeks of age (adult stage), and their lifespan and tumor development were assessed. Irrespective of CR, X-rays shortened lifespan by 38%, and irrespective of irradiation CR extended lifespan by 20%. Thymic lymphoma (TL) and early-occurring non-TL were induced by radiation. The liver and Harderian gland were more susceptible to radiation-induced tumors than the lungs and non-thymic lymphoid tissues (late occurring). CR reduced the risk of hepatocellular carcinoma, late-occurring non-TL, lung tumor, Harderian tumor, and hemangioma but had less impact on TL and early-occurring non-TL. Most notably, the effects of X-rays on induction of lung tumors, late-occurring non-TL and hemangioma were essentially canceled by CR. The ability of CR to prevent late-occurring tumors was the same for non-irradiated and irradiated mice, indicating that the mechanism by which CR influences cancer is independent of irradiation. Our results indicate that adult-onset CR significantly inhibits late-occurring tumors in a tissue-dependent manner regardless of infant radiation exposure.

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Section: Discussionmentioning

confidence: 99%

Cancer prevention by adult‐onset calorie restriction after infant exposure to ionizing radiation in B6C3F1 male mice

Shang¹,

Kakinuma²,

Yamauchi

et al. 2014

Intl Journal of Cancer

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“…had a relatively short follow‐up period, and asthma or other airway diseases without COPD were also included since the study included all subjects using inhaled medications. Smoking status or amount, the most important risk factor for lung cancer, was not evaluated in some previous studies …”

Section: Discussionmentioning

confidence: 99%

Inhaled corticosteroids in COPD and the risk of lung cancer

Lee

Kim

Lee

et al. 2018

Intl Journal of Cancer

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Inhaled corticosteroids (ICS) might reduce the risk of lung cancer by controlling airway inflammation in patients with chronic obstructive pulmonary disease (COPD) because both are associated with chronic inflammation. The objective was to assess the impact of ICS on lung cancer risk reduction in COPD patients. We performed a nested case-control study based on the database of the National Health Insurance Service-National Sample Cohort, a nationally representative cohort of 1,125,691 participants in Korea followed over 11 years. The eligible population was patients aged 30-89 years who were newly diagnosed with COPD and initiated inhaled medications after diagnosis. Cases were defined as individuals diagnosed with lung cancer after the initiation of inhaled medications and were matched with controls by propensity score at a 1:4 ratio. We identified 265 individuals with lung cancer, matched with 1,060 controls. Use of ICS was associated with reduced risk of lung cancer (adjusted hazard ratio [aHR] 0.74, 95% CI 0.57-0.96). The high cumulative ICS dose group, defined as those above the third quartile of ICS dose distribution, had a lower risk of lung cancer than the low cumulative dose group (aHR 0.51, 95% CI 0.34-0.75). The effect of ICS on lung cancer risk reduction was more remarkable in former smokers than current smokers. Additionally, the result was consistent in men regardless of the classification according to ICS use, while it was not significant in women. ICS, particularly at high cumulative dose, might be associated with decreased risk of lung cancer in patients with COPD. Severe COPD frequently warrants treatment with inhaled corticosteroids, which exert immunomodulatory and antiproliferative effects. Despite an association between COPD and increased lung cancer risk, patients on ICS appear to have a reduced likelihood of developing lung cancer. Here, analyzing data from the National Health Insurance Service-National Sample Cohort in Korea, the authors show that ICS use is associated with decreased lung cancer risk in COPD patients. An inverse dose-response relationship was detected, whereby increasing cumulative ICS dose was associated with decreasing lung cancer risk. The effect was most pronounced in men and former smokers.

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“…However, in that case we would expect that there would be an increased risk of lung cancer (or at least no significant and protective effect of ICS use), which was not the case in the observational studies. The influence of protopathic bias was discounted in an observational study evaluating the impact of ICS exposure on lung cancer incidence . This study, which was not included in this review because the study population included subjects with either COPD, asthma or another respiratory condition, reported a significant protective effect of ICS against lung cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Similar to the two observational studies that were included in this review, this protective effect was dose‐dependent. With respect to protopathic bias, those authors performed a sensitivity analysis where exposure to ICS within 3–6 months prior to lung cancer diagnosis was excluded, and the protective effect of ICS persisted . Neither identified observational study used a lagged exposure period to reduce the possibility of protopathic bias in their base‐case analysis; however, Parimon et al .…”

Section: Discussionmentioning

confidence: 99%

Do inhaled corticosteroids protect against lung cancer in patients with COPD? A systematic review

et al. 2016

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Inhaled corticosteroids (ICS) are commonly prescribed to COPD patients, particularly those with more advanced stages of the disease. These patients are also at increased risk of lung cancer. A systematic review was undertaken to identify studies that examined the association between lung cancer risk and ICS therapy in COPD patients. The search strategy was created in MEDLINE and extended to EMBASE as well as other relevant databases. Both randomized controlled trials (RCTs) and observational studies were considered for inclusion. Studies were required to have incident lung cancer or deaths from lung cancer as an outcome in order to be included in the review. Six studies met the inclusion criteria. Two observational studies directly addressed the specific research. Four RCTs presented sufficient data to calculate the relative risk of lung cancer in COPD patients. None of the identified RCTs showed a statistically significant association of ICS use with lung cancer risk. Observational studies showed a protective effect from ICS use, particularly at high doses. Given the observational evidence and the low numbers of lung cancer events in the RCTs, these results may be prone to type II error. The observational studies dealt with very specific patient populations and exposure definitions, which might not have adequately captured the complex relationship between ICS exposure and lung cancer risk. Results from RCTs suggest no effect of ICS on the risk of lung cancer. However, results from observational studies suggest the potential that ICS may confer a protective effect, particularly at high doses.

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Inhaled corticosteroid use and risks of lung cancer and laryngeal cancer

Cited by 45 publications

References 43 publications

Cancer prevention by adult‐onset calorie restriction after infant exposure to ionizing radiation in B6C3F1 male mice

Cancer prevention by adult‐onset calorie restriction after infant exposure to ionizing radiation in B6C3F1 male mice

Inhaled corticosteroids in COPD and the risk of lung cancer

Do inhaled corticosteroids protect against lung cancer in patients with COPD? A systematic review

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