Lung cancer risk and residential radon exposure: A pooling of case-control studies in northwestern Spain

Highlights

• Residential radon is a clear risk factor for lung cancer in ever and never-smokers.

• Radon is a risk factor even at levels considered low by international organizations.

• This risk is found in the different subtypes of non-small cell lung cancer.

• There is an effect modification between residential radon and tobacco consumption.

Abstract

Background

Through a pooled case-control study design, we have assessed the relationship between residential radon exposure and lung cancer risk. Other objectives of the study were to evaluate the different risk estimates for the non-small cell lung cancer histological types and to assess the effect modification of the radon exposure on lung cancer risk by tobacco consumption.

Methods

We collected individual data from various case-control studies performed in northwest Spain that investigated residential radon and lung cancer. Cases had a confirmed anatomopathological diagnosis of primary lung cancer and controls were selected because they were undergoing ambulatory evaluation or surgical procedures that were unrelated to tobacco use. Residential radon was measured using alpha track detectors. Results were analyzed using logistic regression.

Results

3704 participants were enrrolled, 1842 cases and 1862 controls. Data show that lung cancer risk increases with radon exposure, finding a significant association of radon exposure with lung cancer at radon exposures above 50 Bq/m³. The estimated adjusted OR for individuals exposed to concentrations >200 Bq/m³ was 2.06 (95% CI: 1.61–2.64) compared with those exposed to ≤50 Bq/m³. Within a smoking category, lung cancer risk increases markedly as radon concentration increases, reaching an OR of 29.3 (95% CI: 15.4–55.7) for heavy smokers exposed to more than 200 Bq/m.³

Conclusions

This study confirms that residential radon exposure is a risk factor for lung cancer well below action levels established by international organizations. As expected, there is also an effect modification between radon exposure and tobacco consumption.

Introduction

Lung cancer has now become a major public health problem throughout the world, owing to both its high incidence and its high lethality. It is currently considered the most frequently diagnosed cancer as well as the most frequent cause of mortality from cancer worldwide, accounting around 11.6% of total cancer cases and 18.4% of all deaths from cancer in 2018 according to the data published in thee GLOBOCAN report (Bray et al., 2018). In spite of the diagnostic and therapeutic development, unfortunately survival rates have hardly improved in the last decades due to the fact that many of those patients are already diagnosed at advanced stages (De Angelis et al., 2014; Siegel et al., 2018).

It is estimated that tobacco use is responsible for approximately 79% of all lung cancer cases among men and 47% among women, as the leading cause for lung cancer (Lopez et al., 2006), which represents the most relevant modifiable risk factor for this disease. In Spain, 32.5% of the smoking-attributable mortality is due to lung cancer (Perez-Rios et al., 2020). On the other hand, between 20% and 25% of lung cancer cases are found among those people who have never smoked, thereby showing the importance of non-smoking risk factors (Rudin et al., 2009; Sun et al., 2007). Residential radon exposure is the second major contributor to the risk of lung cancer after cigarette smoking and the leading one among never-smokers (U.S. Environmental Protection Agency, 2012). In 1988 radon was identified as a cancer-causing agent by the International Agency for Research on Cancer (IARC) (IARC, 1988) and the World Health Organization (WHO) reported that about 3–15% of all lung cancers worldwide may be attributable to indoor radon (WHO, 2009).

Radon (222Rn) is a chemically inert, colorless, odorless, and tasteless gas which naturally occurs in the environment through the radioactive disintegration of the uranium contained on all rocks and soils (National Research Council, 1999). Outdoors, radon is rapidly degraded into the atmosphere, however, high concentrations of radon can be accumulated in enclosed places such as homes or workplaces (Darby et al., 2001). Radon enters the body through inhalation and its short-life decay products release alpha particles that may cause DNA damage on the lung cells, enhancing lung cancer risk as a result of prolonged exposures (National Research Council, 1999; Yngvenson et al., 1999).

The first evidence linking radon to lung cancer risk came from epidemiological studies conducted on uranium miners (National Research Council, 1999; Keil et al., 2015; Rage et al., 2015; Van Dillen et al., 2011). A greater risk because of radon exposure was also detected for the general population through studies with a case-control design. European and American pooling included some of these studies (Darby et al., 2005; Krewski et al., 2005) which indicate an increase in lung cancer risk by 16% and 11% for each 100 Bq/m³, respectively, proving a linear relationship between exposure to radon and risk of lung cancer. This is similar to the published preliminary results from our group in smokers (Barros-Dios et al., 2002, 2012) and never-smokers (Torres-Durán et al., 2014a,b). Smokers when exposed to large concentrations of radon are more likely to develop lung cancer than smokers who are exposed lesser levels, highlighting the existence of effect modification between smoking and radon exposure (National Research Council, 1999). Nevertheless, this association has been relatively poorly studied.

The aims of the current study were, through a pooled case-control design: 1) to identify the association of residential radon exposure to lung cancer risk for the general population, 2) to know the different risks for histological types of non-small cell lung cancer, and 3) to quantitatively assess the effect modification of the radon exposure and lung cancer risk by tobacco consumption.