Indoor radon exposure increases tumor mutation burden in never-smoker patients with lung adenocarcinoma

Lim, Sun Min; Choi, Jae Woo; Hong, Min Hee; Jung, Dongmin; Lee, Chang Young; Park, Sung Yong; Shim, Hyo Sup; Sheen, Seungsoo; Kwak, Kyeong Im; Kang, Dae Ryong; Cho, Byoung Chul; Kim, Hye Ryun

doi:10.1016/j.lungcan.2019.04.002

Cited by 26 publications

(19 citation statements)

References 36 publications

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“…Thus, the ability to identify responders based on clinical characteristics would be of great clinical significance. Smoking history is a risk factor for pulmonary carcinogenesis, and smoking is known to alter the immune microenvironment and TMB in lung cancer, effects which have been linked with the therapeutic efficacy of immunotherapy (7)(8)(9)(10). However, direct evidence for whether a smoking history is associated with the response to immunotherapy is lacking.…”

Section: Introductionmentioning

confidence: 99%

Impact of Smoking History on Response to Immunotherapy in Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

et al. 2021

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ObjectivesTo evaluate the impact of smoking history on the clinical benefit of immunotherapy in patients with non-small cell lung cancer (NSCLC).MethodsTwenty-three randomized clinical trials and seven real-world studies were included in this meta-analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) and odds ratios for the overall response rate (ORR) were extracted. A fixed-effects or random-effects model was applied to obtain pooled estimates.ResultsData from 16 high-quality trials involving 10,643 NSCLC patients receiving either immunotherapy or chemotherapy/placebo enabled direct comparison of the survival impact of smoking. Anti-PD-1/PD-L1/CTLA-4 immunotherapy was found to significantly prolong OS and PFS as compared to chemotherapy/placebo in smokers (HR for OS, 0.76 [0.69–0.83], P<0.00001; HR for PFS, 0.65 [0.56–0.75], P<0.00001), and these trends were less or not significant in non-smokers (HR for OS, 0.91 [0.78–1.06], P=0.25; HR for PFS, 0.68 [0.45–1.03], P=0.07). Consistent results were obtained for the first-line or second/third-line use of immunotherapy and for non-squamous NSCLC patients only. Furthermore, the data from 7 trials and 7 real-world studies involving 4,777 patients receiving immunotherapy allowed direct comparison of therapeutic outcomes between smokers and non-smokers. Prolonged OS (HR 0.86 [0.75–0.99], P=0.04) and PFS (HR 0.69 [0.60–0.81], P<0.0001) and a higher response rate (ORR 1.20 [0.94–1.53], P=0.15) were observed in smokers compared to non-smokers receiving immunotherapy.ConclusionsImmunotherapy was found to have a greater benefit in NSCLC patients with a smoking history than in those who had never smoked.

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Section: Introductionmentioning

confidence: 99%

Impact of Smoking History on Response to Immunotherapy in Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

et al. 2021

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“…Lung cancer is the 6 th leading overall cause of death and the foremost cause of cancer death in the world. It is understood to be predominantly triggered by chronic inhalation of tobacco smoke and/or radioactive radon ( 222 Rn) gas, often coupled with underlying genetic predispositions 1–6 . Radon is a primary cause of lung cancer in never smokers and the second leading cause in smokers, encompassing an estimated 3–20% of lung cancer deaths worldwide 7,8 .…”

Section: Introductionmentioning

confidence: 99%

Radon exposure is rising steadily within the modern North American residential environment, and is increasingly uniform across seasons

Stanley

Irvine

Jacques

et al. 2019

Sci Rep

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Human-made buildings can artificially concentrate radioactive radon gas of geologic origin, exposing occupants to harmful alpha particle radiation emissions that damage DNA and increase lung cancer risk. We examined how North American residential radon exposure varies by modern environmental design, occupant behaviour and season. 11,727 residential buildings were radon-tested using multiple approaches coupled to geologic, geographic, architectural, seasonal and behavioural data with quality controls. Regional residences contained 108 Bq/m3 geometric mean radon (min < 15 Bq/m3; max 7,199 Bq/m3), with 17.8% ≥ 200 Bq/m3. Pairwise analysis reveals that short term radon tests, despite wide usage, display limited value for establishing dosimetry, with precision being strongly influenced by time of year. Regression analyses indicates that the modern North American Prairie residential environment displays exceptionally high and worsening radon exposure, with more recent construction year, greater square footage, fewer storeys, greater ceiling height, and reduced window opening behaviour all associated with increased radon. Remarkably, multiple test approaches reveal minimal winter-to-summer radon variation in almost half of properties, with the remainder having either higher winter or higher summer radon. This challenges the utility of seasonal correction values for establishing dosimetry in risk estimations, and suggests that radon-attributable cancers are being underestimated.

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“…Rn exposure also correlates with tumor mutation burden (TMB), and subjects with a high exposure have almost twice as many mutations/Mb compared with those with low exposures. Apparently, this mutational signature is associated with defective DNA mismatch repair [ 115 ]. There is also evidence that adjacent cells may sustain damage via a “bystander effect”, phenomenon for which no irradiated cells respond to signals emitted by adjacent irradiated cells [ 116 ].…”

Section: Discussionmentioning

confidence: 99%

Environmental/Occupational Exposure to Radon and Non-Pulmonary Neoplasm Risk: A Review of Epidemiologic Evidence

Mozzoni

Pinelli

Corradi

et al. 2021

IJERPH

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Although Radon (Rn) is a known agent for lung cancer, the link between Rn exposure and other non-pulmonary neoplasms remains unclear. The aim of this review is to investigate the role of Rn in the development of tumors other than lung cancer in both occupational and environmental exposure. Particularly, our attention has been focused on leukemia and tumors related to brain and central nervous system (CNS), skin, stomach, kidney, and breast. The epidemiologic literature has been systematically reviewed focusing on workers, general population, and pediatric population. A weak increase in leukemia risk due to Rn exposure was found, but bias and confounding factors cannot be ruled out. The results of studies conducted on stomach cancer are mixed, although with some prevalence for a positive association with Rn exposure. In the case of brain and CNS cancer and skin cancer, results are inconclusive, while no association was found for breast and kidney cancers. Overall, the available evidence does not support a conclusion that a causal association has been established between Rn exposure and the risk of other non-pulmonary neoplasms mainly due to the limited number and heterogeneity of existing studies. To confirm this result, a statistical analysis should be necessary, even if it is now not applicable for the few studies available.

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Indoor radon exposure increases tumor mutation burden in never-smoker patients with lung adenocarcinoma

Cited by 26 publications

References 36 publications

Impact of Smoking History on Response to Immunotherapy in Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

Impact of Smoking History on Response to Immunotherapy in Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

Radon exposure is rising steadily within the modern North American residential environment, and is increasingly uniform across seasons

Environmental/Occupational Exposure to Radon and Non-Pulmonary Neoplasm Risk: A Review of Epidemiologic Evidence

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