For lifetime non-smokers, lung cancer risk is mainly associated with inhalation exposure to air pollution. For the Chinese population, indoor air pollution due to solid fuel combustion has been the primary source of i...For lifetime non-smokers, lung cancer risk is mainly associated with inhalation exposure to air pollution. For the Chinese population, indoor air pollution due to solid fuel combustion has been the primary source of inhalation exposure for decades. Polycyclic aromatic hydrocarbons （PAHs） are the by-products of incomplete combustion.展开更多
Runs of homozygosity （ROHs） are a class of important but poorly studied genomic variations and may be in- volved in individual susceptibility to diseases. To better understand ROH and its relationship with lung canc...Runs of homozygosity （ROHs） are a class of important but poorly studied genomic variations and may be in- volved in individual susceptibility to diseases. To better understand ROH and its relationship with lung cancer, we performed a genome-wide ROH analysis of a subset of a previous genome-wide case-control study （1,473 cases and 1,962 controls） in a Han Chinese population. ROHs were classified into two classes, based on lengths, intermedi- ate and long ROils, to evaluate their association with lung cancer risk using existing genome-wide single nucleofide polymorphism （SNP） data. We found that the overall level of intermediate ROHs was significantly associated with a decreased risk of lung cancer （odds ratio = 0.63; 95% confidence interval： 0.51-0.77; P = 4.78 × 10-6 ）, while the long ROHs seemed to be a risk factor of lung cancer. We also identified one ROH region at 14q23A that was con- sistently associated with lung cancer risk in the study. These results indicated that ROHs may be a new class of variation which may be associated with lung cancer risk, and genetic variants at 14q23.1 may be involved in the development of lung cancer.展开更多
目的:评估国际肺癌研究协会(International Association for the Study of Lung Cancer,IASLC)分级系统和传统计算机体层成像(computed tomography,CT)影像学特征之间的联系,并构建基于CT影像学特征的预后分层模型。方法:回顾并分析2019...目的:评估国际肺癌研究协会(International Association for the Study of Lung Cancer,IASLC)分级系统和传统计算机体层成像(computed tomography,CT)影像学特征之间的联系,并构建基于CT影像学特征的预后分层模型。方法:回顾并分析2019年1月—2022年5月南京市胸科医院收治的102例原发性病理(p)Ⅰ期(T1N0M0或T2aN0M0)肺腺癌(lung adenocarcinoma,LUAD)患者的病历。根据2020年IASLC分级系统对患者进行分级,比较了不同IASLC组织学分级之间以及复发组和未复发组之间的临床病理和影像学特征。Logistic回归分析用于确定IASLC分级相关的CT征象,并通过多变量Cox回归模型确定患者无病生存期(disease-free survival,DFS)的影响因素。结果:102例LUAD患者分为1级15例(14.7%),2级63例(61.8%)和3级24例(23.5%)。在30.4个月随访期间,16例(15.7%)患者复发。较高的CTR(OR=2.152,95%CI 1.530~3.264,P=0.005)和较高的CT值(OR=3.730,95%CI 2.841~6.353,P=0.001)是较高组织学分级的独立危险因素。联合上述2个独立因素预测IASLC 3级的曲线下面积(area under curve,AUC)为0.912(95%CI 0.877~0.937;P<0.001),与单独使用平均CT值或实变肿瘤比率(consolidation tumor ratio,CTR)的AUC差异无统计学意义。多变量Cox回归分析显示,年龄(HR=1.05,95%CI 1.02~1.09,P=0.003)、CTR(HR=2.81,95%CI 1.16~6.77,P=0.022)、CT值(HR=2.49,95%CI 1.19~5.25,P=0.016)、毛刺征(HR=5.96,95%CI 2.30~15.43,P<0.001)和组织学分级(HR=4.31,95%CI 2.28~8.14,P<0.001)是DFS的独立危险因素。结论:较大的CTR以及较高的平均CT值是较高IASLC组织学分级的独立预测因子。CTR(截断值<0.25和≥0.75)和平均CT值(截断值<-410 HU和≥-210 HU)可用作IASLC分级系统的术前替代物。展开更多
肺癌导致的死亡人数位于各类恶性肿瘤之首,它是对人类健康和生命威胁最大的恶性肿瘤之一。肺癌的TNM分期系统描述了肺癌的生长和扩散等信息,对于指导其临床治疗起了非常重要的作用。目前临床上广泛采用的是国际抗癌联盟(Union for Inter...肺癌导致的死亡人数位于各类恶性肿瘤之首,它是对人类健康和生命威胁最大的恶性肿瘤之一。肺癌的TNM分期系统描述了肺癌的生长和扩散等信息,对于指导其临床治疗起了非常重要的作用。目前临床上广泛采用的是国际抗癌联盟(Union for International Cancer Control,UICC)和美国癌症联合会(American Joint Committee on Cancer,AJCC)于2009年发布的第七版肺癌TNM分期。随着肺癌综合治疗的发展以及临床实践模式的改变,肺癌的疗效及其预后也有了明显的改变,旧的分期标准可能难以满足目前的临床需求。因此,国际肺癌研究协会(international association for the study of lung cancer,IASLC)于2014年就开始进行最新一轮的肺癌TNM分期标准修订研究计划。本次分期研究克服了以往分析数据均为回顾性数据的缺陷,采用囊括了回顾性和前瞻性数据的新数据库。该数据库主要是由1999—2010年间新确诊的94 708名肺癌患者数据组成。通过对该数据库分析研究,国际肺癌研究协会对TNM分期进行了相应的修改,并最终在2015年发表了第八版国际肺癌TNM分期的修订稿。本文就该修订稿的细节进行解读。展开更多
目前国内外学术界采用的是美国癌症联合会（American Joint Commission for Cancer，AJCC）和国际抗癌联盟（Union Internationale Contre le Cancer，UICC）2002年公布的第六版肺癌TNM分期标准，其制定乃基于对德州-安德森医学中心的4...目前国内外学术界采用的是美国癌症联合会（American Joint Commission for Cancer，AJCC）和国际抗癌联盟（Union Internationale Contre le Cancer，UICC）2002年公布的第六版肺癌TNM分期标准，其制定乃基于对德州-安德森医学中心的4351例（1975—1988年）和国立癌症研究所肺癌研究组的968例（1977—1982年）肺癌患者资料的分析。随着手术前分期手段如多层CT、FDG—PET以及内窥镜等技术的发展，以及全球肺癌研究合作的不断增多，第六版分期标准逐渐显卅不足之处。国际肺癌研究联合会（International Association for the Studv of Lung Cancer，IASLC）收集了1990—2000年间，展开更多
Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely unknown.By integr...Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely unknown.By integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants.We identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites.Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific.Functional annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency related.Our results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.展开更多
基金funded by the National Natural Science Foundation of China(41390240 and 41571130010)the 111 Project(B14001)
文摘For lifetime non-smokers, lung cancer risk is mainly associated with inhalation exposure to air pollution. For the Chinese population, indoor air pollution due to solid fuel combustion has been the primary source of inhalation exposure for decades. Polycyclic aromatic hydrocarbons （PAHs） are the by-products of incomplete combustion.
基金supported in part the by National Natural Science Foundation of China(81230067,81270044 and 30901233)Doctoral Fund of Ministry of Education of China(20093234110001)+1 种基金New Century Excellent Talents in University(NCET-10-0178)a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘Runs of homozygosity （ROHs） are a class of important but poorly studied genomic variations and may be in- volved in individual susceptibility to diseases. To better understand ROH and its relationship with lung cancer, we performed a genome-wide ROH analysis of a subset of a previous genome-wide case-control study （1,473 cases and 1,962 controls） in a Han Chinese population. ROHs were classified into two classes, based on lengths, intermedi- ate and long ROils, to evaluate their association with lung cancer risk using existing genome-wide single nucleofide polymorphism （SNP） data. We found that the overall level of intermediate ROHs was significantly associated with a decreased risk of lung cancer （odds ratio = 0.63; 95% confidence interval： 0.51-0.77; P = 4.78 × 10-6 ）, while the long ROHs seemed to be a risk factor of lung cancer. We also identified one ROH region at 14q23A that was con- sistently associated with lung cancer risk in the study. These results indicated that ROHs may be a new class of variation which may be associated with lung cancer risk, and genetic variants at 14q23.1 may be involved in the development of lung cancer.
文摘目的:评估国际肺癌研究协会(International Association for the Study of Lung Cancer,IASLC)分级系统和传统计算机体层成像(computed tomography,CT)影像学特征之间的联系,并构建基于CT影像学特征的预后分层模型。方法:回顾并分析2019年1月—2022年5月南京市胸科医院收治的102例原发性病理(p)Ⅰ期(T1N0M0或T2aN0M0)肺腺癌(lung adenocarcinoma,LUAD)患者的病历。根据2020年IASLC分级系统对患者进行分级,比较了不同IASLC组织学分级之间以及复发组和未复发组之间的临床病理和影像学特征。Logistic回归分析用于确定IASLC分级相关的CT征象,并通过多变量Cox回归模型确定患者无病生存期(disease-free survival,DFS)的影响因素。结果:102例LUAD患者分为1级15例(14.7%),2级63例(61.8%)和3级24例(23.5%)。在30.4个月随访期间,16例(15.7%)患者复发。较高的CTR(OR=2.152,95%CI 1.530~3.264,P=0.005)和较高的CT值(OR=3.730,95%CI 2.841~6.353,P=0.001)是较高组织学分级的独立危险因素。联合上述2个独立因素预测IASLC 3级的曲线下面积(area under curve,AUC)为0.912(95%CI 0.877~0.937;P<0.001),与单独使用平均CT值或实变肿瘤比率(consolidation tumor ratio,CTR)的AUC差异无统计学意义。多变量Cox回归分析显示,年龄(HR=1.05,95%CI 1.02~1.09,P=0.003)、CTR(HR=2.81,95%CI 1.16~6.77,P=0.022)、CT值(HR=2.49,95%CI 1.19~5.25,P=0.016)、毛刺征(HR=5.96,95%CI 2.30~15.43,P<0.001)和组织学分级(HR=4.31,95%CI 2.28~8.14,P<0.001)是DFS的独立危险因素。结论:较大的CTR以及较高的平均CT值是较高IASLC组织学分级的独立预测因子。CTR(截断值<0.25和≥0.75)和平均CT值(截断值<-410 HU和≥-210 HU)可用作IASLC分级系统的术前替代物。
文摘肺癌导致的死亡人数位于各类恶性肿瘤之首,它是对人类健康和生命威胁最大的恶性肿瘤之一。肺癌的TNM分期系统描述了肺癌的生长和扩散等信息,对于指导其临床治疗起了非常重要的作用。目前临床上广泛采用的是国际抗癌联盟(Union for International Cancer Control,UICC)和美国癌症联合会(American Joint Committee on Cancer,AJCC)于2009年发布的第七版肺癌TNM分期。随着肺癌综合治疗的发展以及临床实践模式的改变,肺癌的疗效及其预后也有了明显的改变,旧的分期标准可能难以满足目前的临床需求。因此,国际肺癌研究协会(international association for the study of lung cancer,IASLC)于2014年就开始进行最新一轮的肺癌TNM分期标准修订研究计划。本次分期研究克服了以往分析数据均为回顾性数据的缺陷,采用囊括了回顾性和前瞻性数据的新数据库。该数据库主要是由1999—2010年间新确诊的94 708名肺癌患者数据组成。通过对该数据库分析研究,国际肺癌研究协会对TNM分期进行了相应的修改,并最终在2015年发表了第八版国际肺癌TNM分期的修订稿。本文就该修订稿的细节进行解读。
文摘目前国内外学术界采用的是美国癌症联合会（American Joint Commission for Cancer，AJCC）和国际抗癌联盟（Union Internationale Contre le Cancer，UICC）2002年公布的第六版肺癌TNM分期标准，其制定乃基于对德州-安德森医学中心的4351例（1975—1988年）和国立癌症研究所肺癌研究组的968例（1977—1982年）肺癌患者资料的分析。随着手术前分期手段如多层CT、FDG—PET以及内窥镜等技术的发展，以及全球肺癌研究合作的不断增多，第六版分期标准逐渐显卅不足之处。国际肺癌研究联合会（International Association for the Studv of Lung Cancer，IASLC）收集了1990—2000年间，
基金the Key International(Regional)Cooperative Research Project(No.81820108028)the National Natural Science Foundation of China(Nos.81521004,81922061,81973123,and 81803306)+2 种基金the Science Foundation for Distinguished Young Scholars of Jiangsu(No.BK20160046)the Priority Academic Program for the Development of Jiangsu Higher Education Institutions(Public Health and Preventive Medicine).the National Cancer Institute,National Institutes of Health of USA through grants U01-CA063673,UM1-CA167462,and U01-CA167462.
文摘Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely unknown.By integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants.We identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites.Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific.Functional annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency related.Our results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.
