Lung cancer is currently a serious health-care problem. According to data of the Spanish National Institute of Statistics, it was the cause of 20401 deaths in 2009, becoming the third cause of death in Spain after ischemic heart disease and cerebrovascular diseases. According to sex, there were 17279 deaths in men and 3122 in women; in order, lung cancer was the second and thirteenth cause of death, respectively.1 In addition to its high incidence, it is also highly lethal. According to recent data, 5-year survival after diagnosis ranges from 12% to 16%.2,3 This survival rate has hardly improved in recent decades and early diagnosis of the disease is therefore essential, as are the need to improve primary prevention activities by eliminating its main risk factors and improving treatments.

Lung cancer is a multifactorial disease.4 It is attributed to smoking in 79% of all cases in men and 47% in women.5 It has been reported that exposure to residential radon is the second cause of lung cancer in smokers and the first in never-smokers.6 More and more studies indicate that lung cancer in never-smokers is a different molecular entity than lung cancer in smokers,7–10 and the study of its risk factors is very useful in order to understand its etiology. However, few research studies have exclusively analyzed lung cancer in never-smokers and none, as far as we know, has been specifically aimed at finding out exactly what is the effect of residential radon exposure in these patients.

Radon is a colorless, odorless, insipid gas that appears during the disintegration chain of uranium 238. At semi-disintegration, radon emits radioactive alpha particles that, when they impact with the cells of the pulmonary epithelium, may cause genetic-molecular alterations and ultimately cause cancer. As alpha particles do not penetrate, they release all their energy in a micrometrical space. Radon has a half-life of 3.8 days; therefore its inhalation is barely a health risk. There are, however, descendants of radon that have a very short half-life (especially polonium 214) that represent a true risk for lung cancer. The radon that is exhaled from the Earth's crust tends to become concentrated in the inside of buildings and, therefore, the risk for lung cancer tends to increase in subjects who are exposed to higher concentrations. Galicia and certain areas of the Iberian Peninsula are risk areas due to the geological substrate on which they lie.11–13 For this reason, we consider it especially interesting to analyze the contribution of exposure to residential radon to lung cancer in never-smokers. Previous studies in Galicia have consistently observed that, even at concentrations within recommended levels,12 radon is an important risk factor for lung cancer that could participate in up to 25% of all lung cancer deaths. In Galicia, this could represent one death per day due to this disease.14

The results that are presented in this article are part of a more extensive study (LCRINS – Lung Cancer Risk in Never Smokers), a multicenter study with international projection. All the hospitals in Galicia and one hospital in Asturias participate in this study, whose objective is to identify risk factors for lung cancer in never-smokers and their possible interaction with certain genetic polymorphisms. The specific objective of this study is to report the residential radon concentrations in a series of cases of lung cancer in never-smokers and to correlate them with several characteristics of said cases (sex, age at diagnosis or histologic type).

This study shows that the concentrations of residential radon are high in a series of lung cancer cases in never-smokers. The median observed concentration is 237Bq/m3, while the level considered in need of action by American authorities is situated at 148Bq/m3 and the WHO has recently recommended that levels should not be higher than 100Bq/m3. It has also been observed that there is a tendency for higher concentrations in those cases with large-cell and small-cell histologic types.

The concentration of radon observed among the participants in the study is almost 3 times higher than the average concentration of residential radon observed in almost 2500 homes in Galicia.19 All these homes are part of the Galician Radon Map. Almost 70% of these measurements have been obtained by randomly selecting the participating subjects (and therefore their homes), and the preliminary results were published in 2007.13 The remaining 30% of the homes measured were obtained from direct contact with the general population and controls from 2 studies of cases and controls about radon and lung cancer done by our group.12,20

The studies available today have observed that the risk for lung cancer due to residential radon could be higher in never-smokers compared with smokers. These studies come from the addition of pooling studies from European and American case–control research, with the consequent heterogeneity in the data collection.21,22 In the European pooling study, there was an observed dosage–response relationship between lung cancer risk and the concentration of residential radon in never-smokers. Individuals exposed to more than 400Bq/m3 have 1.7 (95% CI: 1.2–2.3) times more risk for lung cancer compared with those who are exposed to less than 25Bq/m3. The number of subjects in the high exposure level was low.21 Nevertheless, the effect of residential radon in never-smokers has shown conflicting results. Sandler et al.23 observed a non-significant excess risk of 0.141 in never-smokers for every 100Bq/m3. However, this effect was higher than that observed in the total of the analyzed sample. In the American pooling study, the effect of the exposure to residential radon was the same for smokers and never-smokers,22 and the same was observed in the Iowa study.24 In another recently published environmental study among subjects participating in the Cancer Prevention Study II, no effect was found for the exposure to residential radon in never-smokers,25 while Wilcox et al. have observed that the effect of radon on lung cancer was higher in never-smokers than in smokers.26 Studies in miners have also obtained contradictory results.27,28

The results of this study show that never-smoker men and women with lung cancer are exposed to similar concentrations of residential radon. We have not found studies that enable us to compare these results. Initially, there do not seem to be reasons to think of a differential effect, contrary to tobacco. Both risk factors may have different carcinogenic mechanisms. As for age, the cases diagnosed at a later age have higher radon concentrations, although the difference is not significant. One possible explanation would be that radon needs a longer induction period and that, therefore, older subjects have been exposed for longer periods. We also have not found studies that have compared age at diagnosis in never-smoker lung cancer patients.

As for the histologic type, the results agree with other research and previous studies done by our group. The evidence available consistently indicates that radon, as it is a risk factor for lung cancer in all histologic types, should have greater influence in small-cell cancer and in other histologic types (including large-cell carcinoma). The American pooling study had the highest risk for small-cell carcinoma, followed by other histologic types,22 like the European pooling and other studies.26 The same pattern has been observed for studies done in miners.28 This same pattern has recently been observed in a case–control study in Galicia.20

Northwestern Spain, and especially the province of Galicia, provides a unique opportunity to analyze the effect of residential radon exposure in never-smokers. Due to the high concentrations of residential radon produced by the geological characteristics of the subsoil, the conditions for “natural experimentation” enable us to clearly determine the dose–response effect of radon on lung cancer in never-smokers given the high variability in the concentrations. This fact is accentuated by the constructive characteristics of many single-family homes made of granite that contribute to the increased concentrations of interior radon.13 Another study that was carried out in an area of less geological risk for residential radon concentrations did not find an association between radon and lung cancer,29 which reinforces the importance of the characteristics of the subsoil in lung cancer risk attributable to radon gas in the home.

This research presents a series of limitations, including the presentation of the results of the concentrations of residential radon between lung cancer cases without having available the concentrations from controls. In coming months, these results will be made available. We believe, however, that these preliminary data sufficiently illuminate the importance of radon in the etiology of lung cancer in never-smokers. Another limitation is the sample size, although the 69 cases included in the present analysis are a relatively high number when one considers the infrequency of lung cancer in never-smokers. Lastly, other variables may influence in the appearance of lung cancer, such as occupation or exposure to second-hand smoke. Nevertheless, its relative importance in the appearance of lung cancer is much less when compared with the effect of radon.

On the other hand, this present study presents several advantages. Perhaps the most important of these is its multicenter nature, given the low incidence of lung cancer in never-smokers. This fact increases the external validity of the results and achieves a sample size that is sufficiently high enough to obtain precise conclusions about lung cancer risk factors in never-smokers. Another advantage is the ample variability of residential radon concentrations, linked with the fact that the study was done in a risk area, which makes it easier to find out the effect of residential radon in never-smokers. Furthermore, the number of unreturned detectors was very small, with a return rate of more than 85% as a result of the participating researcher's efforts and their follow-up phone calls to the patients. The unreturned detectors have been associated with participants with some type of comprehension problem or those who were in the final phases of life at the time of diagnosis.

The concentrations of residential radon in the cases included are very high, at around 3 times the average residential radon concentration to which the Galician general public is exposed.19 It is therefore necessary to make both the population and the administrations aware of the importance that this gas can have in the development of lung cancer, both in smokers as well as never-smokers, and to promote preventive measures that have been demonstrated to be effective at reducing home exposure to radon.

This study has been financed with a competitive research project grant from the Galician Provincial Government (Xunta de Galicia, ref. 10CSA208057PR).

The authors declare having no conflict of interests.