Ge Xiao, Liu Xing, Xu Wang Hong, Sun Yexiang, Lin Hongbo, Shen Peng, Chen Haiquan, He Na
Department of Epidemiology, School of Public Health, and Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China.
Yinzhou District Center for Disease Control and Prevention, Ningbo City, Zhejiang Province, China.
BMJ Open. 2025 Sep 9;15(9):e104941. doi: 10.1136/bmjopen-2025-104941.
Although lung cancer in never smokers (LCNSs) accounts for an estimated 25% of all lung cancer cases, the temporal trends in LCNS incidence and its broader epidemiological patterns remain poorly understood. Our study examines the temporal trends in LCNS incidence and analyses key epidemiological characteristics, specifically, the trends in mortality rates, survival rates and changes in age at onset to illuminate the reasons for temporal trends in LCNS incidence.
Retrospective population-based cohort study.
Regional electronic health record (EHR) database linked to the cancer registry in eastern China.
A total of 1 080 317 adults who have never smoked were included, among whom 4061 incident lung cancer cases were identified between 1 January 2009 and 31 December 2020.
The temporal trends in LCNS incidence in a large population-based dynamic cohort were estimated, overall and separately by sex, age group and histological types. The broader epidemiological patterns of LCNS, such as trends in mortality rates, survival rates and changes in age at onset, were analysed.
From 2009 through 2020, the incidence of LCNS among men increased significantly from 9.51 to 43.4 per 100 000 (average annual percentage change (AAPC) 10.51%; 95% CI (6.88% to 14.26%)) whereas a sharper increase was observed among women from 3.57 to 51.68 per 100 000 (AAPC 22.39%; 95% CI (18.36% to 26.55%)). The 2-year survival of LCNS improved from 39% in 2010 to 64% in 2018 for men, and from 57% in 2009 to 86% in 2020 for women, while the mortality from LCNS remained stable from 2014 through 2020 (men: AAPC -1.77%; 95% CI (-8.95% to 5.97%); women: AAPC 2.19%; 95% CI (-4.09% to 8.89%)). The increasing trend in LCNS incidence was observed across most of the age groups except the elderly population aged ≥85 years in both sexes and the men aged 45-54 years, but the increase was most evident in the younger population aged <45 years (men: AAPC 21.10%; 95% CI (3.57% to 41.60%); women: AAPC 32.05%; 95% CI (23.73% to 40.92%)). The incidence of adenocarcinoma increased sharply in both sexes, whereas the incidence of non-adenocarcinoma histological types either increased slightly or remained stable. The standardised average age at onset of LCNS decreased significantly over time among women (β=-0.58, robust SE=0.16, p=0.005) but not among men (β=-0.21, SE=0.15, p=0.189).
There is a substantial increase in LCNS incidence, especially among women and young populations. However, the reason for these observed trends remains unclear and warrants investigation.
尽管从不吸烟者肺癌（LCNS）估计占所有肺癌病例的25%，但LCNS发病率的时间趋势及其更广泛的流行病学模式仍知之甚少。我们的研究考察了LCNS发病率的时间趋势，并分析了关键的流行病学特征，具体而言，死亡率、生存率趋势以及发病年龄变化，以阐明LCNS发病率时间趋势的原因。
基于人群的回顾性队列研究。
与中国东部癌症登记处相连的区域电子健康记录（EHR）数据库。
共纳入1080317名从不吸烟的成年人，其中在2009年1月1日至2020年12月31日期间确定了4061例肺癌新发病例。
估计了一个大型基于人群的动态队列中LCNS发病率的时间趋势，总体以及按性别、年龄组和组织学类型分别进行估计。分析了LCNS更广泛的流行病学模式，如死亡率、生存率趋势以及发病年龄变化。
从2009年到2020年，男性LCNS发病率从每10万人9.51例显著增加到43.4例（平均年百分比变化（AAPC）10.51%；95%置信区间（6.88%至14.26%）），而女性的增加更为明显，从每10万人3.57例增加到51.68例（AAPC 22.39%；95%置信区间（18.36%至26.55%））。男性LCNS的2年生存率从2010年的39%提高到2018年的64%，女性从2009年的57%提高到2020年的86%，而LCNS的死亡率在2014年至2020年期间保持稳定（男性：AAPC -1.77%；95%置信区间（-8.95%至5.97%）；女性：AAPC 2.19%；95%置信区间（-4.09%至8.89%））。除了85岁及以上的老年人群以及45 - 54岁的男性外，大多数年龄组都观察到LCNS发病率呈上升趋势，但在年龄小于45岁的年轻人群中增加最为明显（男性：AAPC 21.10%；95%置信区间（3.57%至41.60%）；女性：AAPC 32.05%；95%置信区间（23.73%至40.92%））。两性腺癌的发病率均急剧上升，而非腺癌组织学类型的发病率要么略有上升，要么保持稳定。随着时间的推移，女性LCNS发病的标准化平均年龄显著下降（β = -0.58，稳健标准误 = 0.16，p = 0.005），但男性没有下降（β = -0.21，标准误 = 0.15，p = 0.189）。
LCNS发病率大幅上升，尤其是在女性和年轻人群中。然而，这些观察到的趋势的原因仍不清楚，值得进一步研究。
