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

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 institution.Methods: We analyzed clinical data of 1860 consecutive patients who were newly diagnosed with NSCLC between June 2011 and December 2014.Results: 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 < 0.001) and earlier stage(stage I–II, 44.5% vs. 38.9%, P < 0.001) a= 0.015) compared with ever?smokers. Epidermal growth factor receptor mutations(57.8% vs. 24.4%, Pnd anaplastic lymphoma kinase rearrangements(7.8% vs. 2.8%, P < 0.001) were more common in 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.

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

Lung cancer is the leading cause of cancer-related mortality globally,accounting for 1.8 million deaths in 2020.While the vast majority are caused by tobacco smoking,15%-25%of all lung cancer cases occur in lifelong neversmokers.The 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 hazards.However,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 ever-smokers.Among 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 overemphasized.Additionally,while initial genetic studies largely focused on lung cancer as a whole,recent studies have also identified genetic risk factors for LCINS.This article presents an overview of several environmental factors associated with LCINS,and some of the emerging evidence for genetic factors associated with LCINS.An 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 disease.Conclusive 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.

云南宣威、富源地区非吸烟女性肺癌生存分析

背景与目的云南东部农村地区宣威市、富源县女性居民主要从事农业生产和家务工作,基本不吸烟,但肺癌死亡率却是世界上最高的,而且发病、死亡年龄提前。本研究对宣威、富源非吸烟女性肺癌生存状况及其影响因素进行分析。方法以2006年-2010年被当地省、市、县9家医院新诊断、并纳入"非吸烟女性肺癌病例对照研究项目"的常住户籍女性肺癌病例为研究对象随访至2016年末。通过Life-table法进行全部病例生存分析,评估人群相对生存率和年龄别标化相对生存率。应用Kaplan-Meier法和Cox比例风险模型分别进行单因素生存分析、分层分析和多因素分析。结果随访的1,250例病例中,死亡1,075例,删失175例,随访中位时间为69个月(95%CI:61.9-76.0)。病例平均年龄(54.8±10.9)岁,I期、II期、III期、IV期和未知分期分别占3.5%、8.7%、20.7%、29.7%和37.4%;手术、非手术治疗和未治疗分别占17. 2%、39.0%和43. 8%,组织学、细胞学诊断占51.6%。中位生存时间13.2个月,5年观察生存率、相对生存率、年龄标化相对生存率分别为8.9%(95%CI:7.0-10.6)、9.4%(95%CI:7.6-11.5)和10.1%(95%CI:3.7-20.5)。I期、II期、III期、IV期、未分期5年生存率分别为41.1%、22.4%、5. 3%、1. 3%、11.2%;手术治疗、非手术治疗、未治疗分别为34.8%和3.2%、4.7%;腺癌、鳞癌分别为17.9%和5.6%。省级医院治疗、X线胸部筛查、非农民职业、城镇居住、65岁以下年龄等因素有利于提高生存率,而市县级医院治疗、农民职业、乡村居住、65岁以上年龄等则生存率较低。分层分析显示,任意原发灶-淋巴结-远处转移(tumornode-met a st a si s,T N M)分期,无论腺癌或鳞癌患者,行手术治疗的生存率明显高于非手术治疗;与未治疗病例相比非手术治疗仅在III期显示差异;腺癌生存率大于鳞癌不仅仅因为早期和手术病例较多,在III期、未分期也显示明显生存优势。不同级别医院治疗疗效有明显差异,省级医院治疗的IV期、鳞癌的生存预后明显优于市、县级医院。Cox分析显示治疗方法、TNM分期、治疗医院级别、X线胸部筛查是独立预后因素,其中TNM分期、手术治疗对肺癌患者生存影响较大,而治疗医院级别、X胸部筛查相对较弱。结论宣威、富源非吸烟女性肺癌生存率较低,主要与其诊断时早期病例和手术、综合治疗较少、而未治疗病例较多有关,其次较差的农村社会经济、健康保障等也是生存预后的不利因素。

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

Recently,an increasing number of young never-smokers are diagnosed with lung cancer.The 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 never-smokers.Peripheral blood was collected from 123 never-smoking east-Asian patients diagnosed with lung adenocarcinoma before the age of 40.Whole-exome sequencing(WES)was conducted on genomic DNA extracted from peripheral blood cells.As a result,3,481 single nucleotide variants were identified.By 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 WAS.Patients 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 effects.Gene ontology analysis further showed that these genes with germline mutations were mainly located in nucleo-plasm and associated with DNA repair-related biological processes.The 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.

广州市从不吸烟青少年对电子烟认知及控烟态度

目的了解广东省广州市从不吸烟青少年对电子烟的认知及控烟态度,为新型烟草制品挑战下控烟策略的制定和调整提供初步依据。方法于2017年9月1日—2018年9月30日采用随机抽样方法在广州市抽取1601名从不吸烟青少年进行了问卷调查。结果广州市1601名从不吸烟的青少年中,仅283名(17.68%)从不吸烟青少年未听说过电子烟,自行了解过电子烟的从不吸烟青少年仅261人(16.30%),有395名(24.67%)从不吸烟青少年身边的朋友或亲人使用过电子烟;传统燃烧卷烟与电子烟比较,从不吸烟青少年中认为应禁止未成年人购买传统燃烧卷烟的比例(98.56%)高于电子烟(92.44%),认为应在室内公共场所全面禁止传统燃烧卷烟的比例(95.32%)高于电子烟(80.51%),认为应在室外等候区域等全面禁止传统燃烧卷烟的比例(91.94%)高于电子烟(73.39%),差异均有统计学意义(均P<0.001)。结论电子烟在广州市流行情况可能较想象中严重,且与传统燃烧卷烟相比,从不吸烟青少年对电子烟较为宽容。

Epidermal growth factor receptor mutations detected in tumors from Chinese “never smokers” with lung adenocarcinoma

Lung cancer is the leading cause of cancer-related death in the world as well as in China. It is estimated that approximately 429 000 Chinese individuals may die from lung cancer in 2005, and the mortality rate for lung cancer will double in the next century. 1 Currently, chemotherapy is the a main treatment of advanced and recurrent lung cancer. However, the recent development of tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib may change the therapeutic approaches for this disease. Gefitinib, for example, induces clinical responses in approximately 10% of patients with non-small cell lung cancer (NSCLC) in the USA and Europe, and 26% in Japan. 2,3 A study of gefitinib in 31 patients from Beijing showed an objective tumor response rate of 36%. 4