Lung cancer and residential radon in never-smokers: A pooling study in the Northwest of Spain

Lorenzo-González, María; Ruano-Raviña, Alberto; Torres-Durán, María; Kelsey, Karl T.; Provencio, Mariano; Parente-Lamelas, Isaura; Leiro-Fernández, Virginia; Vidal-García, Iria; Castro‐Añón, Olalla; Martínez, Cristina; Golpe-Gómez, Antonio; Zapata-Cachafeiro, Maruxa; Piñeiro‐Lamas, María; Pérez-Ríos, Mónica; Abal-Arca, José; Montero-Martínez, Carmen; Fernández-Villar, Alberto; Barros-Dios, Juan Miguel

doi:10.1016/j.envres.2019.03.011

Cited by 63 publications

(36 citation statements)

References 27 publications

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“…To date, it is widely accepted that radon and its progeny contribute significantly to excess lung cancer among underground miners [ 40 , 41 ]. Although not nearly comparable to the high dose received by uranium miners, several case-control studies conducted in non-occupational settings showed that low dose radon exposure was associated with higher risk of lung cancer [ 42 – 46 ]. In fact, the National Council on Radiation Protection & Measurements (NCRP) estimated approximately 10,000 deaths per year in the U.S., for an average annual radon exposure of 1 pCi/L [ 40 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Low dose environmental radon exposure and breast tumor gene expression

et al. 2020

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Background The International Agency for Research on Cancer classified radon and its decay-products as Group-1-human-carcinogens, and with the current knowledge they are linked specifically to lung cancer. Biokinetic models predict that radon could deliver a carcinogenic dose to breast tissue. Our previous work suggested that low-dose radon was associated with estrogen-receptor (ER)-negative breast cancer risk. However, there is limited research to examine the role of radon in breast cancer biology at the tissue level. We aim to understand molecular pathways linking radon exposure with breast cancer biology using transcriptome-wide-gene-expression from breast tumor and normal-adjacent tissues. Methods Our study included 943 women diagnosed with breast cancer from the Nurses’ Health Study (NHS) and NHSII. We estimated cumulative radon concentration for each participant up-to the year of breast cancer diagnosis by linking residential addresses with a radon exposure model. Transcriptome-wide-gene-expression was measured with the Affymetrix-Glue-Human-Transcriptome-Array-3.0 and Human-Transcriptome-Array-2.0. We performed covariate-adjusted linear-regression for individual genes and further employed pathway-analysis. All analyses were conducted separately for tumor and normal-adjacent samples and by ER-status. Results No individual gene was associated with cumulative radon exposure in ER-positive tumor, ER-negative tumor, or ER-negative normal-adjacent tissues at FDR < 5%. In ER-positive normal-adjacent samples, PLCH 2—reached transcriptome-wide-significance (FDR < 5%). Gene-set-enrichment-analyses identified 2-upregulated pathways (MAPK signaling and phosphocholine biosynthesis) enriched at FDR < 25% in ER-negative tumors and normal-adjacent tissues, and both pathways have been previously reported to play key roles in ionizing radiation induced tumorigenesis in experimental settings. Conclusion Our findings provide insights into the molecular pathways of radon exposure that may influence breast cancer etiology.

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Section: Discussionmentioning

confidence: 99%

Low dose environmental radon exposure and breast tumor gene expression

et al. 2020

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“…Study-design and setting. A multicenter, hospital-based, case-control study performed in never-smokers, (Lung Cancer Research In Never Smokers-LCRINS) was conducted at 7 hospitals in Galicia, northwest Spain 23 . Patient recruitment took place from January 2011 through July 2019, and only included cases with histologic confirmation of LC who were never-smokers according to the WHO definition, i.e., anyone who has smoked: (1) fewer than 100 cigarettes in his/her lifetime; or (2) less than 1 cigarette per day during a period of no less than 6 months.…”

Section: Methodsmentioning

confidence: 99%

“…All patients were interviewed by trained researchers, who administered a questionnaire used in a number of previous studies 23,24 to collect data on LC risk factors. Exposure to environmental tobacco smoke was assessed through personal interview and included all persons living with the participant in the last 20 years.…”

Section: Data-collectionmentioning

confidence: 99%

Polymorphisms in the BER and NER pathways and their influence on survival and toxicity in never-smokers with lung cancer

Casal-Mouriño

Ruano-Raviña

Torres-Durán

et al. 2020

Sci Rep

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Polymorphisms in DNA repair pathways may play a relevant role in lung cancer survival in never-smokers. Furthermore, they could be implicated in the response to chemotherapy and toxicity of platinum agents. The aim of this study was to evaluate the influence of various genetic polymorphisms in the BER and NER DNA repair pathways on survival and toxicity in never-smoker LC patients. The study included never-smokers LC cases diagnosed from 2011 through 2019, belonging to the Lung Cancer Research In Never Smokers study. A total of 356 never-smokers cases participated (79% women; 83% adenocarcinoma and 65% stage IV). Survival at 3 and 5 years from diagnosis was not associated with genetic polymorphisms, except in the subgroup of patients who received radiotherapy or chemo-radiotherapy, and presented with ERCC1 rs3212986 polymorphism. There was greater toxicity in those presenting OGG1 rs1052133 (CG) and ERCC1 rs11615 polymorphisms among patients treated with radiotherapy or chemo-radiotherapy, respectively. In general, polymorphisms in the BER and NER pathways do not seem to play a relevant role in survival and response to treatment among never-smoker LC patients.

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“…Data from Lorenzo-González et al showed that natural radon is an important risk factor for lung cancer in non-smoking patients exposed to radon levels above 200 Bq/m 3 [42].…”

Section: Radon Exposure and Lung Cancer: Epidemiology And Biomonitoringmentioning

confidence: 99%

Radon Biomonitoring and microRNA in Lung Cancer

Bersimbaev

Pulliero

Bulgakova

et al. 2020

IJMS

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Radon is the number one cause of lung cancer in non-smokers. microRNA expression in human bronchial epithelium cells is altered by radon, with particular reference to upregulation of miR-16, miR-15, miR-23, miR-19, miR-125, and downregulation of let-7, miR-194, miR-373, miR-124, miR-146, miR-369, and miR-652. These alterations alter cell cycle, oxidative stress, inflammation, oncogene suppression, and malignant transformation. Also DNA methylation is altered as a consequence of miR-29 modification induced by radon. Indeed miR-29 targets DNA methyltransferases causing inhibition of CpG sites methylation. Massive microRNA dysregulation occurs in the lung due to radon expose and is functionally related with the resulting lung damage. However, in humans this massive lung microRNA alterations only barely reflect onto blood microRNAs. Indeed, blood miR-19 was not found altered in radon-exposed subjects. Thus, microRNAs are massively dysregulated in experimental models of radon lung carcinogenesis. In humans these events are initially adaptive being aimed at inhibiting neoplastic transformation. Only in case of long-term exposure to radon, microRNA alterations lead towards cancer development. Accordingly, it is difficult in human to establish a microRNA signature reflecting radon exposure. Additional studies are required to understand the role of microRNAs in pathogenesis of radon-induced lung cancer.

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Lung cancer and residential radon in never-smokers: A pooling study in the Northwest of Spain

Cited by 63 publications

References 27 publications

Low dose environmental radon exposure and breast tumor gene expression

Low dose environmental radon exposure and breast tumor gene expression

Polymorphisms in the BER and NER pathways and their influence on survival and toxicity in never-smokers with lung cancer

Radon Biomonitoring and microRNA in Lung Cancer

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