More attention should be devoted to the molecular mechanism and clinical research of lung cancer in never-smokers_West China Medical Journal

Authors：

LUO Wenxin ,  LI Weimin

Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

LI Weimin, Email: weimin003@163.com

Keywords：

Lung cancer; Smoking; Gene mutation; Clinicopathology

DOI：

10.7507/1002-0179.201804011

Video：

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Lung cancer in never-smokers has been identified as a separate disease entity. Notably, the proportion of this distinct disease has been reported to increase in recent decades. Due to its occult onset and lack of clinical specificity, patients with this disease are always diagnosed with advanced stage. This review summarizes the current literatures about the risk factors, clinicopathological characteristics, molecular features, and prognosis of lung cancer in never-smokers, which will enhance our understanding and facilitate the precise management of this distinct disease.

Citation： LUO Wenxin, LI Weimin. More attention should be devoted to the molecular mechanism and clinical research of lung cancer in never-smokers. West China Medical Journal, 2018, 33(4): 371-374. doi: 10.7507/1002-0179.201804011 Copy

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2.	Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
3.	Pelosof L, Ahn C, Gao A, et al. Proportion of never-smoker non-small cell lung cancer patients at three diverse institutions. J Natl Cancer Inst, 2017, 109(7). https://doi.org/10.1093/jnci/djw295.
4.	赵爽, 李镭, 邱志新, 等. 四川地区 2008 年-2013 年 3,663 例肺癌临床病理特征及流行趋势分析. 中国肺癌杂志, 2016, 19(2): 70-76.
5.	Jaeyoung, Cho, Sun, et al. Proportion and clinical features of never-smokers with non-small cell lung cancer. Chin J Cancer, 2017, 36(2): 81-87.
6.	Kang H, Park CW, Kim W, et al. Never-smoker lung cancer is increasing. J Lung Cancer, 2012, 11(2): 89-93.
7.	胡丹婧, 李为民. 不吸烟非小细胞肺癌研究进展. 国际呼吸杂志, 2017, 11(37): 842-848.
8.	Vavalà T, Giaj Levra M, Novello S. Lung cancer in never smokers: a different disease. Curr Respir Care Rep, 2014, 3(1): 26-34.
9.	Lin H, Huang YS, Yan HH, et al. A family history of cancer and lung cancer risk in never-smokers: a clinic-based case-control study. Lung Cancer, 2015, 89(2): 94-98.
10.	He Y, Li Y, Qiu Z, et al. Identification and validation of PROM1 and CRTC2 mutations in lung cancer patients. Mol Cancer, 2014, 13(13): 19.
11.	Lan Q, Hsiung CA, Matsuo K, et al. Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia. Nat Genet, 2012, 44(12): 1330-1335.
12.	Rivera GA, Wakelee H. Lung cancer in never smokers. Adv Exp Med Biol, 2016, 893: 43-57.
13.	Planchard D, Besse B. Lung cancer in never-smokers. Eur Respir J, 2015, 45(5): 1214-1217.
14.	Etzel CJ, Lu M, Merriman K, et al. An epidemiologic study of early onset lung cancer. Lung Cancer, 2006, 52(2): 129-134.
15.	李镭, 刘丹, 张立, 等. 6458 例肺癌患者临床特征及诊疗现状分析. 四川大学学报: 医学版, 2017, 48(3): 352-358.
16.	Govindan R, Ding L, Griffith M, et al. Genomic landscape of non-small cell lung cancer in smokers and never-smokers. Cell, 2012, 150(6): 1121-1134.
17.	Wu K, Zhang X, Li F, et al. Frequent alterations in cytoskeleton remodelling genes in primary and metastatic lung adenocarcinomas. Nat Commun, 2015, 6: 10131.
18.	Cgar N. Comprehensive molecular profiling of lung adenocarcinoma. Nature, 2014, 511(7511): 543-550.
19.	Alexandrov LB, Nik-Zainal S, Wedge DC, et al. Signatures of mutational processes in human cancer. Nature, 2013, 500(7463): 415-421.
20.	Lee YJ, Kim JH, Kim SK, et al. Lung cancer in never smokers: change of a mindset in the molecular era. Lung Cancer, 2011, 72(1): 9-15.
21.	Devarakonda S, Morgensztern D, Govindan R. Genomic alterations in lung adenocarcinoma. Lancet Oncol, 2015, 16(7): E342-E351.
22.	Gou LY, Niu FY, Wu YL, et al. Differences in driver genes between smoking-related and non-smoking-related lung cancer in the Chinese population. Cancer, 2015, 121(Suppl 17): 3069-3079.
23.	中国医师协会肿瘤医师分会, 中国抗癌协会肿瘤临床化疗专业委员会. 中国表皮生长因子受体基因敏感性突变和间变淋巴瘤激酶融合基因阳性非小细胞肺癌诊断治疗指南（2015 版）中华肿瘤杂志, 2015, 37(10): 796-799.
24.	Dearden S, Stevens J, Wu YL, et al. Mutation incidence and coincidence in non small-cell lung cancer: meta-analyses by ethnicity and histology (mutMap) Ann Oncol, 2013, 24(9): 2371-2376.
25.	Wang J, Dong Y, Cai Y, et al. Clinicopathologic characteristics of ALK rearrangements in primary lung adenocarcinoma with identified EGFR and KRAS status. J Cancer Res Clin Oncol, 2014, 140(3): 453-460.
26.	Shi YK, Li JL, Zhang SC, et al. Molecular epidemiology of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology - mainland China subset analysis of the PIONEER study. PLoS One, 2015, 10(11): e0143515.
27.	Pan Y, Wang R, Ye T, et al. Comprehensive analysis of oncogenic mutations in lung squamous cell carcinoma with minor glandular component. Chest, 2014, 145(3): 473-479.
28.	Rekhtman N, Paik PK, Arcila ME, et al. Clarifying the spectrum of driver oncogene mutations in biomarker-verified squamous carcinoma of lung: lack of EGFR/KRAS and presence of PIK3CA/AKT1 mutations. Clin Cancer Res, 2012, 18(4): 1167-1176.
29.	Pan Y, Zhang Y, Li Y, et al. ALK, ROS1 and RET fusions in 1139 lung adenocarcinomas: a comprehensive study of common and fusion pattern-specific clinicopathologic, histologic and cytologic features. Lung Cancer, 2014, 84(2): 121-126.
30.	Hong S, Fang W, Hu Z, et al. A large-scale cross-sectional study of ALK rearrangements and EGFR mutations in non-small-cell lung cancer in Chinese Han population. Sci Rep, 2014, 4: 7268.
31.	Tanaka K, Hida T, Oya Y, et al. Unique prevalence of oncogenic genetic alterations in young patients with lung adenocarcinoma. Cancer, 2017, 123(10): 1731-1740.
32.	Sacher AG, Dahlberg SE, Heng J, et al. Association between younger age and targetable genomic alterations and prognosis in non-small-cell lung cancer. JAMA oncology, 2016, 2(3): 313-320.
33.	Wang R, Hu H, Pan Y, et al. RET fusions define a unique molecular and clinicopathologic subtype of non-small-cell lung cancer. J Clin Oncol, 2012, 30(35): 4352-4359.
34.	Lee SE, Lee B, Hong M, et al. Comprehensive analysis of RET and ROS1 rearrangement in lung adenocarcinoma. Mod Pathol, 2015, 28(4): 468-479.
35.	Chen YF, Hsieh MS, Wu SG, et al. Clinical and the prognostic characteristics of lung adenocarcinoma patients with ROS1 fusion in comparison with other driver mutations in East Asian populations. J Thorac Oncol, 2014, 9(8): 1171-1179.
36.	支修益, 石远凯, 于金明. 中国原发性肺癌诊疗规范 (2015 年版). 中华肿瘤杂志, 2015, 37(1): 67-78.
37.	Subramanian J, Velcheti V, Gao F, et al. Presentation and stage-specific outcomes of lifelong never-smokers with non-small cell lung cancer (NSCLC) J Thorac Oncol, 2007, 2(9): 827-830.
38.	Kawaguchi T, Matsumura A, Fukai S, et al. Japanese ethnicity compared with Caucasian ethnicity and never-smoking status are independent favorable prognostic factors for overall survival in non-small cell lung cancer. J Thorac Oncol, 2010, 5(7): 1001-1010.

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin, 2018, 68(1): 7-30.
2. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
3. Pelosof L, Ahn C, Gao A, et al. Proportion of never-smoker non-small cell lung cancer patients at three diverse institutions. J Natl Cancer Inst, 2017, 109(7). https://doi.org/10.1093/jnci/djw295.
4. 赵爽, 李镭, 邱志新, 等. 四川地区 2008 年-2013 年 3,663 例肺癌临床病理特征及流行趋势分析. 中国肺癌杂志, 2016, 19(2): 70-76.
5. Jaeyoung, Cho, Sun, et al. Proportion and clinical features of never-smokers with non-small cell lung cancer. Chin J Cancer, 2017, 36(2): 81-87.
6. Kang H, Park CW, Kim W, et al. Never-smoker lung cancer is increasing. J Lung Cancer, 2012, 11(2): 89-93.
7. 胡丹婧, 李为民. 不吸烟非小细胞肺癌研究进展. 国际呼吸杂志, 2017, 11(37): 842-848.
8. Vavalà T, Giaj Levra M, Novello S. Lung cancer in never smokers: a different disease. Curr Respir Care Rep, 2014, 3(1): 26-34.
9. Lin H, Huang YS, Yan HH, et al. A family history of cancer and lung cancer risk in never-smokers: a clinic-based case-control study. Lung Cancer, 2015, 89(2): 94-98.
10. He Y, Li Y, Qiu Z, et al. Identification and validation of PROM1 and CRTC2 mutations in lung cancer patients. Mol Cancer, 2014, 13(13): 19.
11. Lan Q, Hsiung CA, Matsuo K, et al. Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia. Nat Genet, 2012, 44(12): 1330-1335.
12. Rivera GA, Wakelee H. Lung cancer in never smokers. Adv Exp Med Biol, 2016, 893: 43-57.
13. Planchard D, Besse B. Lung cancer in never-smokers. Eur Respir J, 2015, 45(5): 1214-1217.
14. Etzel CJ, Lu M, Merriman K, et al. An epidemiologic study of early onset lung cancer. Lung Cancer, 2006, 52(2): 129-134.
15. 李镭, 刘丹, 张立, 等. 6458 例肺癌患者临床特征及诊疗现状分析. 四川大学学报: 医学版, 2017, 48(3): 352-358.
16. Govindan R, Ding L, Griffith M, et al. Genomic landscape of non-small cell lung cancer in smokers and never-smokers. Cell, 2012, 150(6): 1121-1134.
17. Wu K, Zhang X, Li F, et al. Frequent alterations in cytoskeleton remodelling genes in primary and metastatic lung adenocarcinomas. Nat Commun, 2015, 6: 10131.
18. Cgar N. Comprehensive molecular profiling of lung adenocarcinoma. Nature, 2014, 511(7511): 543-550.
19. Alexandrov LB, Nik-Zainal S, Wedge DC, et al. Signatures of mutational processes in human cancer. Nature, 2013, 500(7463): 415-421.
20. Lee YJ, Kim JH, Kim SK, et al. Lung cancer in never smokers: change of a mindset in the molecular era. Lung Cancer, 2011, 72(1): 9-15.
21. Devarakonda S, Morgensztern D, Govindan R. Genomic alterations in lung adenocarcinoma. Lancet Oncol, 2015, 16(7): E342-E351.
22. Gou LY, Niu FY, Wu YL, et al. Differences in driver genes between smoking-related and non-smoking-related lung cancer in the Chinese population. Cancer, 2015, 121(Suppl 17): 3069-3079.
23. 中国医师协会肿瘤医师分会, 中国抗癌协会肿瘤临床化疗专业委员会. 中国表皮生长因子受体基因敏感性突变和间变淋巴瘤激酶融合基因阳性非小细胞肺癌诊断治疗指南（2015 版）中华肿瘤杂志, 2015, 37(10): 796-799.
24. Dearden S, Stevens J, Wu YL, et al. Mutation incidence and coincidence in non small-cell lung cancer: meta-analyses by ethnicity and histology (mutMap) Ann Oncol, 2013, 24(9): 2371-2376.
25. Wang J, Dong Y, Cai Y, et al. Clinicopathologic characteristics of ALK rearrangements in primary lung adenocarcinoma with identified EGFR and KRAS status. J Cancer Res Clin Oncol, 2014, 140(3): 453-460.
26. Shi YK, Li JL, Zhang SC, et al. Molecular epidemiology of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology - mainland China subset analysis of the PIONEER study. PLoS One, 2015, 10(11): e0143515.
27. Pan Y, Wang R, Ye T, et al. Comprehensive analysis of oncogenic mutations in lung squamous cell carcinoma with minor glandular component. Chest, 2014, 145(3): 473-479.
28. Rekhtman N, Paik PK, Arcila ME, et al. Clarifying the spectrum of driver oncogene mutations in biomarker-verified squamous carcinoma of lung: lack of EGFR/KRAS and presence of PIK3CA/AKT1 mutations. Clin Cancer Res, 2012, 18(4): 1167-1176.
29. Pan Y, Zhang Y, Li Y, et al. ALK, ROS1 and RET fusions in 1139 lung adenocarcinomas: a comprehensive study of common and fusion pattern-specific clinicopathologic, histologic and cytologic features. Lung Cancer, 2014, 84(2): 121-126.
30. Hong S, Fang W, Hu Z, et al. A large-scale cross-sectional study of ALK rearrangements and EGFR mutations in non-small-cell lung cancer in Chinese Han population. Sci Rep, 2014, 4: 7268.
31. Tanaka K, Hida T, Oya Y, et al. Unique prevalence of oncogenic genetic alterations in young patients with lung adenocarcinoma. Cancer, 2017, 123(10): 1731-1740.
32. Sacher AG, Dahlberg SE, Heng J, et al. Association between younger age and targetable genomic alterations and prognosis in non-small-cell lung cancer. JAMA oncology, 2016, 2(3): 313-320.
33. Wang R, Hu H, Pan Y, et al. RET fusions define a unique molecular and clinicopathologic subtype of non-small-cell lung cancer. J Clin Oncol, 2012, 30(35): 4352-4359.
34. Lee SE, Lee B, Hong M, et al. Comprehensive analysis of RET and ROS1 rearrangement in lung adenocarcinoma. Mod Pathol, 2015, 28(4): 468-479.
35. Chen YF, Hsieh MS, Wu SG, et al. Clinical and the prognostic characteristics of lung adenocarcinoma patients with ROS1 fusion in comparison with other driver mutations in East Asian populations. J Thorac Oncol, 2014, 9(8): 1171-1179.
36. 支修益, 石远凯, 于金明. 中国原发性肺癌诊疗规范 (2015 年版). 中华肿瘤杂志, 2015, 37(1): 67-78.
37. Subramanian J, Velcheti V, Gao F, et al. Presentation and stage-specific outcomes of lifelong never-smokers with non-small cell lung cancer (NSCLC) J Thorac Oncol, 2007, 2(9): 827-830.
38. Kawaguchi T, Matsumura A, Fukai S, et al. Japanese ethnicity compared with Caucasian ethnicity and never-smoking status are independent favorable prognostic factors for overall survival in non-small cell lung cancer. J Thorac Oncol, 2010, 5(7): 1001-1010.

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More attention should be devoted to the molecular mechanism and clinical research of lung cancer in never-smokers

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