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Lung cancer risk in never-smokers:An overview of environmental and genetic factors

Chinese Journal of Cancer Research 2021年第5期33卷 548-562页

作者： Elvin S Cheng Marianne Weber Julia Steinberg Xue Qin Yu The Daffodil Centre the University of Sydneya joint venture with Cancer Council NSWSydneyNSW 2011Australia

Lung cancer is the leading cause of cancer-related mortality globally,accounting for 1.8 million deaths in *** the vast majority are caused by tobacco smoking,15%-25%of all lung cancer cases occur in lifelong *** International Agency for Research on Cancer(IARC)has classified multiple agents with sufficient evidence for lung carcinogenesis in humans,which include tobacco smoking,as well as several environmental exposures such as radon,second-hand tobacco smoke,outdoor air pollution,household combustion of coal and several occupational ***,the IARC evaluation had not been stratified based on smoking status,and notably lung cancer in never-smokers(LCINS)has different epidemiological,clinicopathologic and molecular characteristics from lung cancer in *** several risk factors proposed for the development of LCINS,environmental factors have the most available evidence for their association with LCINS and their roles cannot be ***,while initial genetic studies largely focused on lung cancer as a whole,recent studies have also identified genetic risk factors for *** article presents an overview of several environmental factors associated with LCINS,and some of the emerging evidence for genetic factors associated with *** increased understanding of the risk factors associated with LCINS not only helps to evaluate a never-smoker’s personal risk for lung cancer,but also has important public health implications for the prevention and early detection of the *** evidence on causal associations could inform longer-term policy reform in a range of areas including occupational health and safety,urban design,energy use and particle emissions,and the importance of considering the impacts of second-hand smoke in tobacco control policy.

关键词： Lung cancer never-smoker risk factor environmental factor genetic factor

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Identification of Germline Mutations in East‑Asian Young never‑smokers with Lung Adenocarcinoma by Whole‑Exome Sequencing

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Phenomics 2023年第2期3卷 182-189页

作者： Fangqiu Fu Xiaoting Tao Zhonglin Jiang Zhendong Gao Yue Zhao Yuan Li Hong Hu Libing Shen Yihua Sun Yang Zhang Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering Fudan University Shanghai Cancer Center270 Dong‑An RoadShanghai 200032China Institute of Thoracic Oncology Fudan UniversityShanghai 200032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032China Key Laboratory of Systems Biology Center for Excellence in Molecular Cell ScienceInstitute of Biochemistry and Cell BiologyShanghai Institutes for Biological SciencesChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China Department of Pathology Fudan University Shanghai Cancer CenterShanghai 200032China International Human Phenome Institutes(Shanghai) Shanghai 200433China

Recently,an increasing number of young never-smokers are diagnosed with lung *** aim of this study is to investigate the genetic predisposition of lung cancer in these patients and discover candidate pathogenic variants for lung adenocarcinoma in young *** blood was collected from 123 never-smoking east-Asian patients diagnosed with lung adenocarcinoma before the age of ***-exome sequencing(WES)was conducted on genomic DNA extracted from peripheral blood *** a result,3,481 single nucleotide variants were *** bioinformatical tools and the published gene list associated with genetic predisposition of cancer,pathogenic variants were detected in ten germline genes:ATR,FANCD2,FANCE,GATA2,HFE,MSH2,PDGFRA,PMS2,SDHB,and *** with pathogenic variants were more likely to occur in females(9/10,90.0%)and have stage IV lung adenocarcinoma(4/10,40%).Furthermore,germline muta-tions in 17 genes(ASB18,B3GALT5,CLEC4F,COL6A6,CYP4B1,C6orf132,EXO1,GATA4,HCK,KCP,NPHP4,PIGX,PPIL2,PPP1R3G,RRBP1,SALL4,and TTC28),which occurred in at least two patients,displayed potentially pathogenic *** ontology analysis further showed that these genes with germline mutations were mainly located in nucleo-plasm and associated with DNA repair-related biological *** study provides spectrum of pathogenic variants and functional explanation for genetic predisposition of lung adenocarcinoma in young never-smokers,which sheds a light on prevention and early diagnosis of lung cancer.

关键词： Lung adenocarcinoma Germline mutation never-smoker Young age DNA repair

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Proportion and clinical features of never-smokers with non-small cell lung cancer

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Chinese Journal of Cancer 2017年第2期36卷 81-87页

作者： Jaeyoung Cho Sun Mi Choi Jinwoo Lee Chang-Hoon Lee Sang-Min Lee Dong-Wan Kim Jae-Joon Yim Young Tae Kim Chul-Gyu Yoo Young Whan Kim Sung Koo Han Young Sik Park Department of Internal Medicine Seoul National University HospitalSeoul 110-744Republic of Korea Department of Thoracic and Cardiovascular Surgery Seoul National University HospitalSeoul 110-744Republic of Korea

Background: The proportion of never?smokers with non?small cell lung cancer(NSCLC) is increasing, but that in Korea has not been well addressed in a large population. We aimed to evaluate the proportion and clinical features of never?smokers with NSCLC in a large single ***: We analyzed clinical data of 1860 consecutive patients who were newly diagnosed with NSCLC between June 2011 and December ***: Of the 1860 NSCLC patients, 707(38.0%) were never?smokers. The proportions of women(83.7% vs. 5.6%) and adenocarcinoma(89.8% vs. 44.9%) were higher among never?smokers than among ever?smokers. Significantly more never?smokers were diagnosed at a younger median age(65 vs. 68 years, P smokers. Epidermal growth factor receptor mutations(57.8% vs. 24.4%, Pnd anaplastic lymphoma kinase rearrangements(7.8% vs. 2.8%, P never?smokers, whereas Kirsten rat sarcoma viral oncogene homolog mutations(5.8% vs. 9.6%, P ntly encountered in never?smokers than in ever?smokers. never?smokers showed longer su= 0.021) were less frequervival after adjust?ing for the favorable effects of younger age, female sex, adenocarcinoma histology, better performance status, early stage disease, being asymptomatic at diagnosis, received antitumor treatment, and the presence of driver mutations(hazard ratio, 0.624; 95% confidence interval, 0.460–0.848; P = 0.003).Conclusions: More than one?third of the Korean patients with NSCLC were never?smokers. NSCLC in never?smokers had different clinical characteristics and major driver mutations and resulted in longer overall survival compared with NSCLC in ever?smokers.

关键词： Non-small cell lung carcinoma never-smoker Epidermal growth factor receptor KRAS Prognosis

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