Novel Genetic Associations Between Lung Cancer and Indoor Radon Exposure

Choi, Jung Ran; Koh, Shin Ok; Park, Sung Yong; Kim, Hye Ryun; Lee, Hyojin; Kang, Dae Ryong

doi:10.15430/jcp.2017.22.4.234

Cited by 9 publications

(5 citation statements)

References 30 publications

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“…Concerning the molecular alterations, TP53 mutations were less common in our Rn-exposed cohort (20%) in comparison to NSCLC patients of our non-exposed group (64%) and in the AACR project (50.3%) [ 36 ]. Our results are in line with the findings of a large review of Ruano-Ravina et al including 578 individuals reporting a frequency of TP53 mutations in 26% in uranium miners and 24% in environmental Rn-exposed patients [ 22 ], and with Choi et al in a Rn-exposed Asian cohort (21%) [ 20 ]. In summary, Rn-exposed people showed less TP53 mutations and neither we nor others found specific Rn-induced mutations.…”

Section: Discussionsupporting

confidence: 93%

“…Rn exposures measured for our cohort with >300 Bq/m 3 in 81.8% of the available cases were higher than in other studies [ 20 , 23 , 33 ] and far exceed the WHO recommended limit of 100 Bq/m 3 [ 5 ]. This emphasizes Umhausen as an area with extensive environmental Rn exposure.…”

Section: Discussioncontrasting

confidence: 57%

“…McDonald et al described KRAS mutations as more frequent in Rn-exposed uranium miners [ 37 ]. Choi et al described KRAS mutations in 5.0% of their Rn-exposed study population [ 20 ]. The limited numbers hamper our results, but differences might well be due to differences in the investigated cohorts.…”

Section: Discussionmentioning

confidence: 99%

“…The largest investigation found that epidermal growth factor receptor (EGFR), tumor protein p53 (TP53), NK2 homeobox1 (NKX 2.1), phosphatase and tensin homolog (PTEN), chromodomain helicase DNA binding protein 7 (CHD7), discoidin domain receptor tyrosine kinase 2 (DDR2), lysine methyltransferase 2C (MLL3, approved abbr. is KMT2C), chromodomain helicase DNA binding protein 5 (CHD5), FAT atypical cadherin 1 (FAT1) and serine/threonine/tyrosine interacting like 2 (DUSP27, now: STYXL2), LAK receptor tyrosine kinase (ALK), ret proto-oncogene (RET), AKT serine/threonine kinase 1 (AKT1), B-Raf proto-oncogene, serine/threonine kinase (BRAF), catenin beta 1(CTNNB1), erb-b2 receptor tyrosine kinase 2 (ERBB2), KRAS proto-oncogene, GTPase (KRAS), mitogen-activated protein kinase kinase 1 (MAP2K1), MET proto-oncogene, receptor tyrosine kinase (MET), NRAS proto-oncogene, GTPase (NRAS), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) out of 37 cancer susceptive genes related to LCINS were associated with Rn exposure [ 20 ]. The results of those molecular investigations are summarized in Table 1 [ 7 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

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Molecular Characteristics of Radon Associated Lung Cancer Highlights MET Alterations

Gamerith

Kloppenburg

Mildner

et al. 2022

Cancers

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Effective targeted treatment strategies resulted from molecular profiling of lung cancer with distinct prevalent mutation profiles in smokers and non-smokers. Although Rn is the second most important risk factor, data for Rn-dependent driver events are limited. Therefore, a Rn-exposed cohort of lung cancer patients was screened for oncogenic drivers and their survival and genetic profiles were compared with data of the average regional population. Genetic alterations were analysed in 20 Rn-exposed and 22 histologically matched non-Rn exposed LC patients using targeted Next generation sequencing (NGS) and Fluorescence In Situ Hybridization (FISH). Sufficient material and sample quality could be obtained in 14/27 non-exposed versus 17/22 Rn-exposed LC samples. Survival was analysed in comparison to a histologically and stage-matched regional non-exposed lung cancer cohort (n = 51) for hypothesis generating. Median overall survivals were 83.02 months in the Rn-exposed and 38.7 months in the non-exposed lung cancer cohort (p = 0.22). Genetic alterations of both patient cohorts were in high concordance, except for an increase in MET alterations and a decrease in TP53 mutations in the Rn-exposed patients in this small hypothesis generating study.

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Section: Discussionsupporting

confidence: 93%

Section: Discussioncontrasting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Molecular Characteristics of Radon Associated Lung Cancer Highlights MET Alterations

Gamerith

Kloppenburg

Mildner

et al. 2022

Cancers

View full text Add to dashboard Cite

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“…However, the role of TP53 in the molecular response to radon exposure may be relevant to the bystander effect, wherein TP53 may mediate the inhibition of response signals coming from irradiated cells [103]. Additionally, other key lung cancer-related genes may also be mutated by radon exposure, including EGFR and phosphatase and tensin homolog (PTEN), but the exact mechanisms remain to be characterized [113].…”

Section: Prominent Cancer Genes Affected By Radonmentioning

confidence: 99%

Oncogenes and Carcinogenesis

Erkekoğlu¹

2019

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Pınar Erkekoglu was born in Ankara, Turkey. She graduated from Hacettepe University Faculty of Pharmacy (BS). Later, she received her MSci and PhD degrees in Toxicology. She completed part of her PhD studies in Grenoble, France, at the Université Joseph Fourier and at CEA/INAC/LAN after receiving full scholarship from both the Erasmus Scholarship Program and CEA. She worked as a post-doc and a visiting associate at the MIT Biological Engineering Department. She has been working as an associate professor in Hacettepe University Faculty of Pharmacy, Department of Pharmaceutical Toxicology, since 2013. Her main interests are carcinogenesis, endocrine disrupting chemicals, oxidative stress, and aromatic amines. She has published more than 140 papers in national and international journals. She has been a European registered toxicologist since 2014. Preface XIII Section 1 Introduction to Oncogene Concept Chapter 1 Introductory Chapter: Interactions between Environmental Chemicals and KRAS Oncogene in Different Cancers -Special Focus on Colorectal, Pancreatic, and Lung Cancers by Pinar Erkekoglu Section 2 Oncogenes and Circadian Clock Chapter 2 A Molecular Link between the Circadian Clock, DNA Damage Responses, and Oncogene Activation

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Single‐cell transcriptome analysis deciphers the CD74‐mediated immune evasion and tumour growth in lung squamous cell carcinoma with chronic obstructive pulmonary disease

Wang,

Li,

Yang

et al. 2024

Clinical & Translational Med

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BackgroundChronic obstructive pulmonary disease (COPD) contributes to the incidence and prognosis of lung cancer. The presence of COPD significantly increases the risk of lung squamous cell carcinoma (LSCC). COPD may promote an immunosuppressive microenvironment in LSCC by regulating the expression of immune‐inhibitory factors in T cells, although the mechanisms remain unclear. In this study, we aimed to decipher the tumour microenvironment signature for LSCC with COPD at a single‐cell level.MethodsWe performed single‐cell RNA sequencing on tumour tissues from LSCC with or without COPD, then investigated the features of the immune and tumour cells. We employed multiple techniques, including multispectral imaging, flow cytometry, tissue microarray analysis, survival analysis, co‐culture systems and in vitro and in vivo treatment experiments, to validate the findings obtained from single‐cell analyses.ResultsLSCC with COPD showed increased proportions of tumour‐associated macrophages (TAMs) and higher levels of CD8+ T cell exhaustion molecules, which contributed to an immunosuppressive microenvironment. Further analysis revealed a critical cluster of CD74+ tumour cells that expressed both epithelial and immune cell signatures, exhibited a stronger capacity for tumorigenesis and predicted worse overall survival. Notably, migration inhibitory factor (MIF) secreted by TAMs from LSCC with COPD may promote the activation of CD74. MIF‐CD74 may interact with CD8+ T cells and impair their anti‐tumour activity by regulating the PI3K‐STAT3‐programmed cell death‐1 ligand 1 signalling pathway, facilitating tumour proliferation and immune evasion.ConclusionsOur comprehensive picture of the tumour ecosystem in LSCC with COPD provides deeper insights into relevant immune evasion mechanisms and potential targets for immunotherapy.Highlight Our results demonstrated higher proportions of tumour‐associated macrophages (TAMs) and higher levels of exhaustion molecules in CD8+ T cells in the microenvironment of LSCC with COPD. CD74+tumour cells were associated with poor disease prognosis. Migration inhibitory factor (MIF)‐CD74 may interact with CD8+ T cells and impair their anti‐tumour activity by regulating the PI3K‐STAT3‐PD‐L1 signalling pathway, facilitating immune evasion.

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Novel Genetic Associations Between Lung Cancer and Indoor Radon Exposure

Cited by 9 publications

References 30 publications

Molecular Characteristics of Radon Associated Lung Cancer Highlights MET Alterations

Molecular Characteristics of Radon Associated Lung Cancer Highlights MET Alterations

Oncogenes and Carcinogenesis

Single‐cell transcriptome analysis deciphers the CD74‐mediated immune evasion and tumour growth in lung squamous cell carcinoma with chronic obstructive pulmonary disease

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