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this study has recruited more than 400 cases of LC in never-smokers with an equal number of controls&#44; making it an important source of epidemiological data in this subgroup of LC cases&#46; Moreover&#44; the study provides a model that might serve as a basis for other multicenter studies&#44; a highly desirable design in the investigation of rare diseases&#46; The main findings of the LCRINS study&#44; focusing primarily on residential radon&#44; are highlighted and discussed below&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Residential radon is the second most important risk factor for LC after smoking&#44; and the most important in never-smokers&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a> Other significant risk factors for LC include certain occupations that involve exposure primarily to asbestos&#44; polycyclic aromatic hydrocarbons &#40;diesel exhaust&#41;&#44; silica dust&#44; or heavy metals&#44; and environmental exposure to tobacco&#46; However&#44; only a small proportion of the population is employed in risk occupations &#40;a risk that has decreased since environmental exposure to tobacco smoke among workers in the bar and restaurant sector has been eliminated&#41;&#46; Environmental exposure to tobacco smoke is a quantitatively smaller risk than indoor radon&#44; and is less ubiquitous&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Galicia&#44; along with regions of Madrid&#44; Extremadura and Castile-Leon&#44; are areas with high radon concentrations&#44; due to the geological characteristics of the subsoil&#46; Other studies have suggested that the greatest numbers of cases of LC in female never-smokers occurred in the province of Ourense&#44; which may be due to exposure to indoor radon&#44; although this was not measured&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The World Health Organization sets the action level of radon at 100<span class="elsevierStyleHsp" style=""></span>Bq per cubic meter&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a> while the United States Environmental Protection Agency sets it at 148<span class="elsevierStyleHsp" style=""></span>Bq per cubic meter&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a> The action level is understood as the lowest concentration at which radon significantly increases the risk of LC&#46; 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2&#46;42&#59; 95&#37; CI&#58; 1&#46;45&#8211;4&#46;06&#41;&#44; indicating that radon is a risk factor for LC&#46; These results suggest that to induce LC&#44; never-smokers must be exposed to higher radon concentrations than smokers&#46; This study also showed evidence of an interaction between residential radon and environmental exposure to tobacco smoke&#46; A detailed analysis of the cases reveals that subjects diagnosed before the age of 60 years were exposed to a higher concentration of residential radon than those diagnosed at older ages&#44; suggesting that exposure to a very high concentration of radon could cause LC to develop earlier&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a> Our analysis of histological types showed that residential radon appears to be more closely associated with small cell cancer and other less common histological types&#44; such as large cell LC&#46; Nevertheless&#44; exposure to radon is associated with all histological types of LC in never-smokers&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">10&#44;11</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The LCRINS study also showed that there may be an association between residential radon and mutations or alterations in LC driver genes&#46; We found no differences in residential radon concentrations between patients with and without EGFR mutations&#44; but we did find close to significant differences in radon exposure in patients with the exon 19 deletion compared to patients with the L858R single-point substitution mutation&#44; who were less exposed to radon &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;057&#41;&#46; We also found that subjects with ALK translocation had almost twice the radon exposure as subjects without ALK translocation&#44; although the results were not significant<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a> &#40;the proportion of ALK-positive subjects is low&#41;&#46; We will have to wait for the results of future studies to see if these findings are confirmed or not&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Genes conferring sensitivity to LC&#44; such as GSTM1 and GSTT1&#44; seem to modulate exposure to residential radon to a certain extent&#44; and&#44; similar to findings in smokers&#44; studies performed in Galicia and other regions indicate that subjects with any of these gene deletions exposed to the same concentrations of radon had a greater risk of lung cancer&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">13&#44;14</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">In view of the accumulated evidence&#44; we propose that scales predicting the risk of LC death or incidence should include exposure to radon&#44; in addition to tobacco consumption and the many other variables that are already included&#44; but which do not show the same degree of causal association as seen for residential radon&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Radon is a risk factor for LC&#44; both in smokers and never-smokers&#46; It should be considered as a cause of LC when this disease is detected in a never-smoker&#44; particularly in areas with high exposure to radon&#46; From a practical point of view&#44; studies such as this highlight the usefulness of multicenter research in respiratory medicine for relatively unusual diseases such as LC in never-smokers or small cell LC&#44; in which we began a similar study in 2015&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0055" class="elsevierStylePara elsevierViewall">The LCRINS study was partially funded by the Government of Galicia &#40;10CSA208057PR&#41;&#46; Part of the study was performed with a Fulbright grant for senior researchers awarded to Alberto Ruano Ravi&#241;a &#40;PRX14&#47;00365&#41;&#46; The protocol was approved by the Clinical Research Ethics Committee of Galicia &#40;2010&#47;295&#41;&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">LCRINS investigators</span><p id="par0060" class="elsevierStylePara elsevierViewall">Carmen Montero Mart&#237;nez &#40;Corunna&#41;&#44; Iria Vidal Garc&#237;a &#40;Corunna&#41;&#44; Olalla Castro A&#241;&#243;n &#40;Lugo&#41;&#44; Margarita Amenedo &#40;Corunna&#41;&#44; Antonio Golpe G&#243;mez &#40;Santiago&#41;&#44; Francisco J Gonz&#225;lez Barcala &#40;Santiago&#41;&#44; Isaura Parente Lamelas &#40;Ourense&#41;&#44; Jos&#233; Abal Arca &#40;Ourense&#41;&#44; &#193;ngeles Rodr&#237;guez &#40;Pontevedra&#41;&#44; Mar&#237;a Torres-Dur&#225;n &#40;Vigo&#41;&#44; Virginia Leiro Fern&#225;ndez &#40;Vigo&#41;&#44; Mariano Provencio Pulla &#40;Majadahonda&#41;&#44; Rosirys Guzm&#225;n Taveras &#40;Oviedo&#41;&#44; Cristina Mart&#237;nez &#40;Oviedo&#41; y Mar&#237;a Jos&#233; Mejuto Mart&#237; &#40;Ferrol&#41;&#46;</p></span></span>"
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Editorial
Residential Radon and Risk of Lung Cancer in Never-Smokers
Radón residencial y riesgo de cáncer de pulmón en nunca fumadores
Alberto Ruano-Ravinaa,b,
Corresponding author
alberto.ruano@usc.es

Corresponding author.
, Alberto Fernández-Villarc, Juan M. Barros-Diosa,b,d
a Área de Medicina Preventiva y Salud Pública, Universidad de Santiago de Compostela, Santiago de Compostela, La Coruña, Spain
b CIBER de Epidemiología y Salud Pública (CIBERESP), Spain
c Servicio de Neumología, Hospital Álvaro Cunqueiro, Vigo, Pontevedra, Spain
d Servicio de Medicina Preventiva, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, La Coruña, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Scientific evidence suggests that lung cancer &#40;LC&#41; in never-smokers is a different molecular entity to LC in smokers&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">1&#44;2</span></a> The Lung Cancer Risk in Never-Smokers &#40;LCRINS&#41; study&#44; a multicenter case control study competitively funded by the Government of Galicia&#44; began in January 2011&#46; Ten hospitals participated in 3 autonomous communities &#40;Galicia&#44; Asturias&#44; and Madrid&#41;&#46; The aim of the study was to determine LC risk factors in never-smokers&#44; looking particularly at residential radon&#44; and the initial results were published in <span class="elsevierStyleSmallCaps">Archivos de Bronconeumolog&#237;a</span> in 2012&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Six years later&#44; this study has recruited more than 400 cases of LC in never-smokers with an equal number of controls&#44; making it an important source of epidemiological data in this subgroup of LC cases&#46; Moreover&#44; the study provides a model that might serve as a basis for other multicenter studies&#44; a highly desirable design in the investigation of rare diseases&#46; The main findings of the LCRINS study&#44; focusing primarily on residential radon&#44; are highlighted and discussed below&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Residential radon is the second most important risk factor for LC after smoking&#44; and the most important in never-smokers&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a> Other significant risk factors for LC include certain occupations that involve exposure primarily to asbestos&#44; polycyclic aromatic hydrocarbons &#40;diesel exhaust&#41;&#44; silica dust&#44; or heavy metals&#44; and environmental exposure to tobacco&#46; However&#44; only a small proportion of the population is employed in risk occupations &#40;a risk that has decreased since environmental exposure to tobacco smoke among workers in the bar and restaurant sector has been eliminated&#41;&#46; Environmental exposure to tobacco smoke is a quantitatively smaller risk than indoor radon&#44; and is less ubiquitous&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Galicia&#44; along with regions of Madrid&#44; Extremadura and Castile-Leon&#44; are areas with high radon concentrations&#44; due to the geological characteristics of the subsoil&#46; Other studies have suggested that the greatest numbers of cases of LC in female never-smokers occurred in the province of Ourense&#44; which may be due to exposure to indoor radon&#44; although this was not measured&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The World Health Organization sets the action level of radon at 100<span class="elsevierStyleHsp" style=""></span>Bq per cubic meter&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a> while the United States Environmental Protection Agency sets it at 148<span class="elsevierStyleHsp" style=""></span>Bq per cubic meter&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a> The action level is understood as the lowest concentration at which radon significantly increases the risk of LC&#46; These risk levels are based on a European study that included over 7000 cases and 14<span class="elsevierStyleHsp" style=""></span>000 controls and revealed a significant linear risk of developing LC due to exposure to residential radon&#44; namely&#44; a 16&#37; increase in risk per 100<span class="elsevierStyleHsp" style=""></span>Bq&#47;m<span class="elsevierStyleSup">3</span> increase in indoor radon concentration&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Most of the research performed on residential radon before the start of the LCRINS study had included cases of LC in smokers and former smokers&#46; The LCRINS study confirmed that the risk of LC was also greater in never-smokers&#44; and that this risk was significant at concentrations higher than 200<span class="elsevierStyleHsp" style=""></span>Bq per cubic meter<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a> compared to the risk in subjects exposed to less than 100<span class="elsevierStyleHsp" style=""></span>Bq per cubic meter &#40;OR&#58; 2&#46;42&#59; 95&#37; CI&#58; 1&#46;45&#8211;4&#46;06&#41;&#44; indicating that radon is a risk factor for LC&#46; These results suggest that to induce LC&#44; never-smokers must be exposed to higher radon concentrations than smokers&#46; This study also showed evidence of an interaction between residential radon and environmental exposure to tobacco smoke&#46; A detailed analysis of the cases reveals that subjects diagnosed before the age of 60 years were exposed to a higher concentration of residential radon than those diagnosed at older ages&#44; suggesting that exposure to a very high concentration of radon could cause LC to develop earlier&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a> Our analysis of histological types showed that residential radon appears to be more closely associated with small cell cancer and other less common histological types&#44; such as large cell LC&#46; Nevertheless&#44; exposure to radon is associated with all histological types of LC in never-smokers&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">10&#44;11</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The LCRINS study also showed that there may be an association between residential radon and mutations or alterations in LC driver genes&#46; We found no differences in residential radon concentrations between patients with and without EGFR mutations&#44; but we did find close to significant differences in radon exposure in patients with the exon 19 deletion compared to patients with the L858R single-point substitution mutation&#44; who were less exposed to radon &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;057&#41;&#46; We also found that subjects with ALK translocation had almost twice the radon exposure as subjects without ALK translocation&#44; although the results were not significant<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a> &#40;the proportion of ALK-positive subjects is low&#41;&#46; We will have to wait for the results of future studies to see if these findings are confirmed or not&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Genes conferring sensitivity to LC&#44; such as GSTM1 and GSTT1&#44; seem to modulate exposure to residential radon to a certain extent&#44; and&#44; similar to findings in smokers&#44; studies performed in Galicia and other regions indicate that subjects with any of these gene deletions exposed to the same concentrations of radon had a greater risk of lung cancer&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">13&#44;14</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">In view of the accumulated evidence&#44; we propose that scales predicting the risk of LC death or incidence should include exposure to radon&#44; in addition to tobacco consumption and the many other variables that are already included&#44; but which do not show the same degree of causal association as seen for residential radon&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Radon is a risk factor for LC&#44; both in smokers and never-smokers&#46; It should be considered as a cause of LC when this disease is detected in a never-smoker&#44; particularly in areas with high exposure to radon&#46; From a practical point of view&#44; studies such as this highlight the usefulness of multicenter research in respiratory medicine for relatively unusual diseases such as LC in never-smokers or small cell LC&#44; in which we began a similar study in 2015&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0055" class="elsevierStylePara elsevierViewall">The LCRINS study was partially funded by the Government of Galicia &#40;10CSA208057PR&#41;&#46; Part of the study was performed with a Fulbright grant for senior researchers awarded to Alberto Ruano Ravi&#241;a &#40;PRX14&#47;00365&#41;&#46; The protocol was approved by the Clinical Research Ethics Committee of Galicia &#40;2010&#47;295&#41;&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">LCRINS investigators</span><p id="par0060" class="elsevierStylePara elsevierViewall">Carmen Montero Mart&#237;nez &#40;Corunna&#41;&#44; Iria Vidal Garc&#237;a &#40;Corunna&#41;&#44; Olalla Castro A&#241;&#243;n &#40;Lugo&#41;&#44; Margarita Amenedo &#40;Corunna&#41;&#44; Antonio Golpe G&#243;mez &#40;Santiago&#41;&#44; Francisco J Gonz&#225;lez Barcala &#40;Santiago&#41;&#44; Isaura Parente Lamelas &#40;Ourense&#41;&#44; Jos&#233; Abal Arca &#40;Ourense&#41;&#44; &#193;ngeles Rodr&#237;guez &#40;Pontevedra&#41;&#44; Mar&#237;a Torres-Dur&#225;n &#40;Vigo&#41;&#44; Virginia Leiro Fern&#225;ndez &#40;Vigo&#41;&#44; Mariano Provencio Pulla &#40;Majadahonda&#41;&#44; Rosirys Guzm&#225;n Taveras &#40;Oviedo&#41;&#44; Cristina Mart&#237;nez &#40;Oviedo&#41; y Mar&#237;a Jos&#233; Mejuto Mart&#237; &#40;Ferrol&#41;&#46;</p></span></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Ruano-Ravina A&#44; Fern&#225;ndez-Villar A&#44; Barros-Dios JM&#46; Rad&#243;n residencial y riesgo de c&#225;ncer de pulm&#243;n en nunca fumadores&#46; Arch Bronconeumol&#46; 2017&#59;53&#58;475&#8211;476&#46;</p>"
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Article information
ISSN: 15792129
Original language: English
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