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B. Melloni



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    MS 23 - Risk Factors: Beyond the Cigarette (ID 41)

    • Event: WCLC 2015
    • Type: Mini Symposium
    • Track: Prevention and Tobacco Control
    • Presentations: 1
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      MS23.01 - Radon and Lung Cancer (ID 1949)

      14:20 - 14:35  |  Author(s): B. Melloni

      • Abstract
      • Presentation

      Abstract:
      Radon exposure is recognized as the second cause of lung cancer, after active cigarette smoking (1,2). Each year, 15 000 to 21 000 lung cancer deaths are estimated for the consequence of radon exposure in USA. In Europe, 18 000 deaths are attributable to radon, around 9 % of deaths from lung cancer. Atmospheric concentrations of natural radon gas vary importantly due to concentration of [226]Ra and [232]Th, present in soil of some geographic areas. Most of the radon in indoor spaces of houses and other dwellings is derived from the inert gas transfer from the soil or rock. Short-lived radioactive progeny from inhaled radon, polonium-214 and polonium-218 induce emission of alpha particles (2 protons and 2 neutrons) that directly damage DNA and can induce lung cancer. Radon progenies are inhaled either as free particles, or attached to airborne particles, as dust. The adverse effect of radon has been described since the fifteenth century in the Ore Mountains of Eastern Europe. As early as the 20[th] century, radon was identified a cause of lung cancer in miners in Eastern Europe. Large epidemiological studies on miners showed a link between lung cancer risk and radon exposure at high concentration. In 1988, International Agency for Research on Cancer (IARC) recognized radon, as a group 1 carcinogen, based on the results of epidemiological studies in uranium miners. The risk was correlated to radon exposure in eleven cohort studies in non-smoker and smoker miners, with a sub-multiplicative interaction between smoking and radon (3). In 1970s, it was recognized that the population could be exposed to radon in indoor environments, including home and dwellings. An association between the risk of lung cancer and residential radon concentration during the previous 30 years was outlined. Epidemiological case-control studies have reported clear evidence of a relation between lung cancer incidences in the general population and radon indoor exposure, at an average annual concentration above 200 Bq/m[3] (4,5,6). A dose-response model is used without a threshold value, but this concept is matter of controversy for low dose To improve the statistical power, pooled case-control studies have been made in the USA, Europe and China, after variable adjustment for sex, smoking habits (Table 1). The combined estimation from the pooling studies showed an increase of 10% per 100 Bq/m[3 ](7). In the European pooled case-control studies, the estimated lung cancer risk, at 0, 100, and 400 Bq/m[3], was 25.8, 29.9, 42.3 for current smokers (15-24 cigarettes per day) versus 1.0, 1.2, 1.6 for lifelong non-smokers (6). The relationship between active smoking and radon exposure seems to be synergic. The same relation is observed in patients with lung cancer exposed both to radon and environmental tobacco smoke (ETS). In Spain, a case control-study demonstrates that ETS exposure at home upgrades significantly the risk in individuals with radon exposure than 200 Bq/m[3 ](7). Concerning histological types of lung cancers observed, an excessive relative risk for small-cell lung cancer was first reported among the underground miners. In fact, all the histological types are present, most common being adenocarcinoma and squamous cell carcinomas. A recent study in Spain, in never-smoker cases exposed to radon, finds that the most frequent histology is adenocarcinoma, as now observed in non-smoker patients (8). The exact mechanism of lung cancer induced by alpha particles is not known. Alpha particles can cause DNA damage, chromosome aberrations, and generate reactive oxygen species. The results are a cell cycle modification, an up- and down-regulation of cytokines, and an increased potential for carcinogenesis. Despite these promising investigations on a mutation hotspot in one codon of the TP53 gene and in other regions, any molecular fingerprint of alpha particles has been identified in specific genes involved in lung cancer carcinogenesis. Reducing and controlling this natural radiation, the second cause of lung cancer, is paramount in the general population, especially in radon prone area. The WHO guideline has proposed a reference level of 100 Bq/m[3] (2.7 pCi/L) to reduce the risk of lung cancer in the population (9). In the USA, the Environmental Protection Agency action level is 148 Bq/m[3] (4 pCi/L) for the home. In Sweden, 35-40 % of lung cancer attributable to radon could be prevented if in all homes or dwellings radon concentrations over 100 Bq/m[3] were lowered to 100 Bq/m[3] (10). Buildings or houses with high radon concentration must be identified. New constructions should be “radon-proof”. Many strategies have been proposed to reduce indoor radon levels in the home. In conclusion, radon is the second leading cause of lung cancer among smokers and a major cause in non-smokers. Radon exposure must be identified in the population to reduce the level of exposure to individuals. Preventive measures are necessary for new homes in a high radon area. Smoking cessation is also important to reduce the risk of lung cancer from radon exposure. Bibliography 1. Samet JM, Avila-Tang E, Boffetta P, et al. Lung cancer in never smokers: clinical epidemiology and environmental risk factors. Clin Cancer Res 2009;15(18):5626-45. 2. Tirmarche M, Harrison JD, Laurier D et al. ICPR, 2010. Lung cancer risk from radon and progeny and statement on radon. ICPR publications 115, Ann. ICPR 40(1). 3. Lubin JH, Boice JD, Edling JC et al. 1994. Radon and lung cancer risk: A joint analysis of 11 underground miner studies. Publication No. 96-3644. US National Institutes of Health, Bethesda, MD, USA. 4. Krewski D, Lubin JH, Zielenski JM at al. Radon and risk of lung cancer: a combined analysis of 7 North-American case-control studies. Epidemiology 2005;16:137-45. 5. Lubin JH, Wang ZY, Boice JD Jr et al. Risk of lung cancer and residential radon in China: pooled results of two studies. Int J Cancer 2004;109:132-7. 6. Darby S, Hill D, Deo H et al. Residential radon and lung cancer-detailed results of a collaborative analysis of individual data on 7,148 persons with lung cancer and 14,208 persons without lung cancer from 13 epidemiological studies in Europe. Scand J Work Environ Health 2006;32(suppl 1):1-83. 7. Torres-Duràn M, Ruano-Ravina A, Parente-Lamelas I et al. Lung cancer in never smokers. A case-control study in a radon prone area (Galicia, Spain). Eur Respir J 2014;44(4):994-1001. 8. Torres-Duràn M, Ruano-Ravina A, Parente-Lamelas I et al. Residential radon and lung cancer characteristics in never smokers. Int J Radiat Biol. 2015 May 13:1-24. 9.World Health Organization. Handbook on indoor radon. A public health perspective. WHO Geneva, Switzerland, 2009. 10. Axelsson G, Anderssson EM, Barregard L. Lung cancer risk from radon exposure in dwellings in Sweden: how many cases can be prevented if radon levels are lowered? Cancer Causes Control 2015; 26 (4): 541-7.

      Geographic area Population Controls Cases Relative risk per 100 Bq/m[3 ](95% CI)
      USA, Canada 7 studies 4 966 3 662 1.10 (0.99-1.26)
      China 2 studies 1 995 1 050 1.13 (1.01-1.26)
      Europe 13 studies 14 208 7 148 1.08 (1.03-1.16)
      Table 1: Pooled analysis of case-control studies of indoor radon exposure, based on measured concentration radon (4-6).

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