Cancer Letters

Cancer Letters

Volume 487, 1 September 2020, Pages 21-26
Cancer Letters

Lung cancer survival in never-smokers and exposure to residential radon: Results of the LCRINS study

https://doi.org/10.1016/j.canlet.2020.05.022Get rights and content

Highlights

  • Lung cancer never-smoker patients appear to have a longer median survival than do ever-smokers.

  • Median survival in never-smokers was higher with lower age at diagnosis, adenocarcinoma, presence of mutations and earlier stage.

  • No differences were found for median survival among never-smokers by residential radon concentration.

Abstract

We aimed to evaluate lung cancer survival in never-smokers, both overall and specifically by sex, exposure to residential-radon, age, histological type, and diagnostic stage.

We included lung cancer cases diagnosed in a multicentre, hospital-based, case-control-study of never-smoker patients, diagnosed from January-2011 to March-2015 (Lung Cancer Research In Never Smokers study).

369 never-smokers (79% women; median age 71 years; 80% adenocarcinoma; 66% stage IV) were included. Median overall survival, and at one, 3 and 5 years of diagnosis was 18.3 months, 61%, 32% and 22%, respectively. Higher median survival rates were obtained for: younger age, adenocarcinoma, actionable mutations, and earlier-stage at diagnosis. Higher indoor radon showed a higher risk of death in multivariate analysis.

Median lung cancer survival in never-smokers seems higher than that in ever-smokers. Patients with actionable mutations have a significantly higher survival. Higher indoor-radon exposure has a negative effect on survival.

Introduction

Lung cancer is a major public health problem, in that it ranks as the leading cause of cancer-related death and causes approximately 388,000 and 1.4 million deaths per annum in Europe and worldwide respectively [1,2]. In the last decade, the number of deaths due to lung cancer has decreased in both sexes, albeit more markedly so in men, owing to women's late incorporation into the smoking habit [3]. While the main risk factor for lung cancer is smoking habit [4], exposure to residential radon is the second leading cause of this disease in smokers and the leading cause in never-smokers [5]. Up to 15% of lung cancers in men and 53% of lung cancers in women are not attributable to smoking habit, with lung cancer in never-smokers being considered a different clinical entity [6,7].

Consequently, approximately 10%–30% of all lung cancers occur in never-smokers [8,9], a phenomenon that tends to be more common in women having a median age at diagnosis of around 69 years, with adenocarcinoma being the predominant histological type [10,11]. Similarly, the presence of mutations in epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) rearrangements are both more frequent among never-smokers.

Overall lung cancer survival is low and has hardly improved in recent years, ranging from 10% to 20% at 5 years of diagnosis [7]. In terms of never-smoker-specific lung cancer survival, the few studies published point to a better survival rate among this group than among ever-smokers. The studies covered in a recent review report median survival figures of 5–23.9 months in smokers versus 7.7–44.6 months in never-smokers [12]. Similarly, the survival rate at 5 years of diagnosis among never-smokers with localised cancer stage was 55.6% [13]. Furthermore, sex and age at diagnosis are known to influence survival, with older-aged men presenting with more comorbidities and higher treatment-related mortality rates than do younger patients [14]. However, the single most influential factor in survival is stage at diagnosis: it is the most important prognostic variable and, as such, accounts for survival rate among never-smokers being low, since most are diagnosed in advanced stages [15].

As mentioned above, among never-smokers exposure to residential radon assumes vital importance. While recent studies show that there is an association between exposure to radon and presence of lung cancer in never-smokers (particularly, if concentrations are higher than 200 Bq/m3), it is not known how such exposure might affect the survival of such never-smoker cases [16], since there are no studies in print.

Accordingly, the aim of this study was to evaluate lung cancer survival in never-smokers, both overall and specifically by sex, exposure to residential radon, age at diagnosis, histological type, and stage at diagnosis. To this end, we analysed data drawn from a series of never-smoker cases recruited in a multicentre hospital-based study in Galicia (Lung Cancer Research In Never Smokers/LCRINS study) [[17], [18], [19]], a Spanish region which is also a high radon-risk area.

Section snippets

Study design and setting

A multicentre, hospital-based, case-control study was conducted on patients from 7 hospitals in north-west Spain (Galicia): patient recruitment took place from January 2011 to March 2015. This present study only included cases drawn from the above case-control study. All the cases included were patients with histologically confirmed lung cancer, and were never-smokers according to the WHO definition, namely, anyone who has smoked: 1) fewer than 100 cigarettes in his/her lifetime; or 2) less

Results

The study covered a total of 369 never-smoker patients (Table 1), 79% of whom were women. Median age at diagnosis was 67 years for men and 72 years for women. The most frequent histological type was adenocarcinoma (294 cases – 80%) and the most frequent stage at diagnosis was stage IV (66%). The median residential radon concentration (available for 306 patients) was 186 Bq/m3. Passive smoking exposure was observed in 155 patients (41,9%), and there were no significant differences on survival at

Discussion

Median lung cancer survival in never-smokers was 18.3 months. Some variables were associated with a higher 5-year survival apart from that already known (chemotherapy, radiotherapy, surgery or stage at diagnosis). These variables were a younger age, with younger patients, histological type, and presence of EGFR or ALK mutations. Of note, we found a better survival at 3 and 5-years of follow-up for those patients having lower residential radon concentrations (i.e. <300 Bq/m3), and this is the

Funding

This paper was funded by the following competitive research grants awarded to the individual case-control studies, which are part of this pooled study:

  • Galician Regional Authority (Xunta de Galicia): 10CSA208057PR “Risk factors of lung cancer in never smokers: a multicentre case-control study in the Northwest of Spain.” 2010. Spain.

  • Carlos III Institute of Health (Instituto de Salud Carlos III), Ministry of Science and Innovation of Spain, grant number PI03/1248. 2003. Spain.

  • Carlos III Institute

Declaration of competing interest

The authors declare that there are no conflicts of interest.

References (27)

  • L.A. Torre et al.

    Global cancer statistics, 2012

    Ca - Cancer J. Clin.

    (2015)
  • R.L. Siegel et al.

    Cancer statistics

    Ca - Cancer J. Clin.

    (2018)
  • WHO et al.

    Handbook on Indoor Radon: a Public Health Perspective

    (2009)
  • Cited by (11)

    • Quantitative evaluation of radon, tobacco use and lung cancer association in an occupational cohort with 27 follow-up years

      2022, Ecotoxicology and Environmental Safety
      Citation Excerpt :

      However, corroborative evidence from other lines of evidence about indoor radon exposure are complicated, because risk from such exposures is likely to be small due to the low radon levels in most homes, furthermore estimation of cumulative lifetime radon exposure in this setting is unlikely to be accurate (Cheng et al., 2021; Council et al., 1999). To our knowledge, no previous studies have reported on the relation of indoor radon exposure to lung cancer risk separately for initial exposure in childhood and adulthood, which highlights the importance of examining this question in an occupational setting as reported here (Casal-Mourino et al., 2020; Cheng et al., 2021; Darby et al., 2005; Gray et al., 2009). On the other hand, in this cohort, we are the first group to report that radon-related lung cancer risk increase with age at last exposure, even after adjustment for tobacco use.

    • Short- and long-term survival outcomes among never smokers who developed lung cancer

      2021, Cancer Epidemiology
      Citation Excerpt :

      Additionally, they typically have fewer co-morbidities and an adenocarcinoma diagnosis [5]. Radon has been cited by the United States Environmental Protection Agency (USEPA) and World Health Organization (WHO) as a leading cause of lung cancer among never smokers ([6,7] and it has recently been reported that indoor radon exposure may have a negative effect on survival [8]. A number of review articles and meta- analyses have further implicated other risk factors for lung cancer among never smokers.

    View all citing articles on Scopus
    1

    This paper forms part of the work leading to Ana Casal-Mouriño’s PhD degree.

    View full text