Cancer Letters

Cancer Letters

Volume 426, 10 July 2018, Pages 57-62
Cancer Letters

Mini-review
Residential radon and small cell lung cancer. A systematic review

https://doi.org/10.1016/j.canlet.2018.04.003Get rights and content

Highlights

  • Radon exposure increases the risk of small cell lung cancer (SCLC).

  • SLCL is the lung cancer histological type most closely linked with radon exposure.

  • The different contribution of radon and tobacco on the onset of SCLC is unknown.

Abstract

Residential radon exposure is considered the second cause of lung cancer and the first in never smokers. Nevertheless, the association between the different histological types of lung cancer and radon is not completely clear, and radon effect on small cell lung cancer is not completely understood. We aim to asses the effect of residential radon exposure on the risk of small cell lung cancer (SCLC) in general population and miners through a systematic review applying predefined inclusion and exclusion criteria. 16 studies were included. Most of them point to a relationship between indoor radon and SCLC, though some investigations show no association. When comparing the risk of SCLC due to radon exposure with NSCLC, it can be observed that an increased risk for SCLC is present. Small cell lung cancer seems to be the histological type of lung cancer most tightly related with residential radon.

Introduction

Lung cancer is a serious health problem today. According to GLOBOCAN 2012, the annual number of new cases in the world is around 1,825,000, with a total of annual deaths of 1,590,000, being the first cause of death in developed countries [1]. In Europe, it represents 26.3% of all cancer deaths [2]. 5-year survival ranges between 15 and 20% in developed countries according to recent data [3]. Lung cancer histological subtypes are usually classified in non-small cell cancer (NSCLC) and small cell lung cancer (SCLC). This classification is based on the neoplastic cell characteristics, as well as in its different behaviour, evolution and response to treatment.

The epidemiology of small cell lung cancer has been poorly studied because it comprises around 14% of all lung cancer cases, far from the frequency of adenocarcinoma or squamous cell carcinoma [4]. Although the incidence of small cell lung cancer is decreasing, the incidence in women with respect to males is increasing, with a male/female ratio of 1:1, compared to the historical 1:3 [5]. This fact has been correlated with the general decrease in tobacco consumption in males, which is the main risk factor for this pathology, compared to the increase in the prevalence of tobacco consumption in women.

Small cell lung cancer is the lung cancer type with the worst prognosis. It has a 5-year survival of 10% in cases with limited stage and only 4.6% at two years in cases diagnosed with extended disease [6]. In both situations, survival rate is slightly higher in women compared to men. In addition, chemotherapy and/or radiotherapy have barely evolved in the last 30 years, and the same occurs with cytostatic drugs used, without a second line of treatment showing an increased relevant survival. There are currently promising treatments for this disease with novel agents such as rovalpituzumab, nivolumab or lurbinectedin, but their specific role and impact on the outcome has to be defined [7,8].

SCLC is the lung cancer type most associated with tobacco consumption [9], but little studies have analyzed the influence of other risk factors different than tobacco, such as indoor radon. Radon is a chemical element in the group of noble gases. It is a product of the disintegration of radium, from which different isotopes descend. It ultimately comes from the Uranium content in the rocks of the earth crust and therefore its concentration is directly related with the uranium concentration on these rocks. Therefore, its presence is heterogeneous worldwide. Radon is an odorless, colorless and tasteless gas. Residential radon is the second most important risk factor for lung cancer, after tobacco, and the first in never smokers as recognized by WHO and the US Environmental Protection Agency [10]. Although it was initially associated only with occupational characteristics (workers in uranium mines, wolfram, etc.), it was subsequently associated with an increase in the incidence of lung cancer [11] in general population. Radon disintegration emits alpha radiation which damage cells on the lung lining, producing mutations. The recommended method of measurement of indoor radon consists in putting at home (preferably in the main bedroom) an alpha-track type detector for a period of three months or more. This device registers the number of alpha particles impacts of radon and short-lived radon descendants and afterwards the impacts are counted in a specific microscope. Radon concentration is measured in becquerels per cubic metre, being a becquerel the production of one alpha particle in a volume of 1 cubic metre in a second. Some studies have shown some association between radon and p53, ALK (anaplastic lymphoma kinase) or EGFR (epidermal growth factor receptor) alterations [12,13], but few studies have analyzed the influence of radon in different histological types of lung cancer, and there is some suggestion that small cell lung cancer might be the histological type most associated with radon exposure.

We aim to know the effect of radon on small cell lung cancer through a systematic review of the scientific literature.

Section snippets

Literature research

We performed a literature research in PubMed (Medline) and EMBASE following PRISMA methodology [14]. To retrieve information, we used a predefined search strategy employing a combination of MeSH terms (radon; small cell lung cancer; lung neoplasm; residential radon) complemented with free text. We also searched in the databases of the Center of Reviews and Dissemination (CRD databases) of the York University and on the Cochrane Library. Latest European, American and Spanish Clinical Guidelines

Search results

A description of the search process appears in Fig. 1. We obtained 438 papers through the literature search and after reading all the abstracts we selected 35 papers for full-text reading. 16 fullfilled the established inclusion criteria, and their characteristics appear in Table 2. We included 11 case-control studies [[17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27]]; 3 pooling studies in Europe and North America [11,28,29] and 2 cohort studies [30,31] in miners. The total

Discussion

To our knowledge, this is the first systematic review focused exclusively on the effect of radon exposure on small cell lung cancer risk. The available studies suggest that this is the histological type of lung cancer most related with radon exposure. This effect seems to occur both in miners' studies and also in general population studies. Though some investigations have not reached a statistically significant association or do not even show a p-value, the investigations with better design and

Conflicts of interest

The authors declare not to have any conflict of interest.

Funding

This paper has been partially funded by a grant from the Instituto de Salud Carlos III. PI15/01211. “Small cell lung cancer, risk factors and genetic susceptibility. A multicenter case-control study in Spain (Small Cell Study)”.

References (37)

  • R. Govindan et al.

    Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database

    J Clin Oncol Off J Am Soc Clin Oncol

    (2006 Oct 1)
  • M. Früh et al.

    Small-cell lung cancer (SCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

    Ann Oncol Off J Eur Soc Med Oncol

    (2013 Oct)
  • A. Rossi et al.

    Current and future therapeutic approaches for the treatment of small cell lung cancer

    Expert Rev. Anticancer Ther.

    (2018 Mar 20)
  • Surveillance, epidemiology, and end results program. Cancer stat facts: lung and bronchus cancer [Internet]

  • OMS | El radón y sus efectos en la salud [Internet]. WHO. [cited 2017 Jan 24]. Available from:...
  • S. Darby et al.

    Radon in homes and risk of lung cancer: collaborative analysis of individual data from 13 European case-control studies

    BMJ

    (2005 Jan 29)
  • A. Ruano-Ravina et al.

    Residential radon, EGFR mutations and ALK alterations in never-smoking lung cancer cases

    Eur. Respir. J.

    (2016 Nov)
  • A. Ruano-Ravina et al.

    Is there a specific mutation of p53 gene due to radon exposure? A systematic review

    Int. J. Radiat. Biol.

    (2009 Jul)
  • Cited by (43)

    • SCLC: Epidemiology, Risk Factors, Genetic Susceptibility, Molecular Pathology, Screening, and Early Detection

      2023, Journal of Thoracic Oncology
      Citation Excerpt :

      Several environmental and occupational exposures and hormonal factors have been suggested to play a role in SCLC. In many populations, residential exposure to radon is the second most import risk for lung cancer after cigarette smoking.44 Prior research suggested that residential radon is associated with a marked increased risk of SCLC: the excess of relative risk per each 100 Bq/m3 was 31.2% (12.8%–60.6%), higher than for other lung cancer histology subtypes at 2.6% (0%–10%).44

    • Residential Radon and Small Cell Lung Cancer. Final Results of the Small Cell Study

      2022, Archivos de Bronconeumologia
      Citation Excerpt :

      For those with a similar tobacco habit, the increase in radon exposure seems to increase importantly the risk of lung cancer. It is important to highlight the high sample size of the present study compared to other studies performed before.17 The linear association observed between radon and lung cancer risk was also observed in other previous studies such as the one by Darby et al.9; Blot et al.19; Pershagen et al.18; Svensson et al.19; Saccomanno et al.20 and Barros-Dios et al.10 These studies support the findings of the present study which were detailed in a systematic review.18

    View all citing articles on Scopus

    This work is part of the research conducting to the PhD Degree of Ángeles Rodríguez Martínez.

    View full text