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The review summarizes evidence across gene expression profiles, germ-line polymorphisms, and somatic gene mutations, including reported ethnic and sex/gender differences. It also outlines how lung cancer epidemiology mirrors past cigarette use patterns and briefly surveys treatment options for both groups.",{"@graph":69,"@context":121},[70,84,104],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/genetic-differences-between-smokers-and-never-smokers-with-lung-cancer-review/383294/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":98,"encodingFormat":97,"isAccessibleForFree":99,"interactionStatistic":100},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/genetic-differences-between-smokers-and-never-smokers-with-lung-cancer-review/383294.png","ImageObject",300,407,{"name":92,"@type":93},"anakgang17","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-24",true,{"@type":101,"interactionType":102,"userInteractionCount":4},"InteractionCounter",{"@type":103},"ViewAction",{"@type":105,"mainEntity":106},"FAQPage",[107,113,117],{"name":108,"@type":109,"acceptedAnswer":110},"Why are smoking patterns closely linked to lung cancer epidemiology?","Question",{"text":111,"@type":112},"Smoking is a major lung cancer risk factor, so geographic mortality trends follow historical cigarette smoking patterns, with changes across generations and countries.","Answer",{"name":114,"@type":109,"acceptedAnswer":115},"How does lung cancer differ between smokers and never-smokers?",{"text":116,"@type":112},"Differences are reported across histological types, environmental risk factors, and genetic features, including gene expression, germ-line polymorphisms, and gene mutations, as well as ethnic and sex/gender differences.",{"name":118,"@type":109,"acceptedAnswer":119},"What histological categories of lung cancer are discussed?",{"text":120,"@type":112},"The text divides lung cancer into non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC), and further describes NSCLC subtypes such as adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.","https://schema.org",{"og:url":83,"og:type":123,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":125,"canonical":83},"index,follow",{"doc_id":127,"site_id":62},383294,1790255724,{"code":4,"msg":5,"data":130},{"doc_id":127,"user_id":131,"nickname":92,"user_avatar":132,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":4,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":138,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":128,"read_time":41},962090883568,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","TYPE Review  \nPUBLISHED 02 February 2023 DOI 10.3389/fimmu.2023.1063716  \nOPEN ACCESS  \nEDITED BY  \nPatrick C. Gedeon, Dana–Farber Cancer Institute, United States  \nREVIEWED BY  \nJustina Ucheojor Onwuka, International Agency For Research On Cancer (IARC), France  \nYing Chen,  \nKunming Medical University, China  \n*CORRESPONDENCE Piotr Ku´snierczyk  \n [piotr.kusnierczyk@hirszfeld.pl](piotr.kusnierczyk@hirszfeld.pl)  \nSPECIALTY SECTION  \nThis article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology  \nRECEIVED 07 October 2022  \nACCEPTED 12 January 2023  \nPUBLISHED 02 February 2023  \nCITATION  \nKu´snierczyk P (2023) Genetic differences between smokers and never-smokers with lung cancer.  \nFront. Immunol. 14:1063716 .  \ndoi: 10.3389/fimmu.2023.1063716  \nCOPYRIGHT  \n© 2023 Ku´snierczyk. This is an open-access article distributed under the terms of the  \nCreative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nGenetic differences between smokers and never-smokers with lung cancer  \nPiotr Ku´snierczyk*  \nLaboratory of Immunogenetics and Tissue Immunology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland  \nSmoking is a major risk factor for lung cancer, therefore lung cancer epidemiological trends reflect the past trends of cigarette smoking to a great extent. The geographic patterns in mortality closely follow those in incidence. Although lung cancer is strongly associated with cigarette smoking, only about 15% of smokers get lung cancer, and also some never-smokers develop this malignancy. Although less frequent, lung cancer in never smokers is the seventh leading cause of cancer deaths in both sexes worldwide. Lung cancer in smokers and never-smokers differs in many aspects: in histological types, environmental factors representing a risk, and in genes associated with this disease. In this review, we will focus on the genetic differences between lung cancer in smokers versus never-smokers: gene expression, germ-line polymorphisms, gene mutations, as well as ethnic and gender differences. Finally, treatment options for smokers and never-smokers will be briefly reviewed.  \nKEYWORDS  \nlung cancer, genetics, immunology, ethnic differences, sex/gender differences, therapy  \nSaru mo ki kara ochiru [(Even monkeys fall from trees; a Japanese proverb (1)]  \n1 Introduction  \nLung cancer is the leading cause of cancer mortality globally. In 2019, there were almost 24 million cancer cases worldwide, and 10 million deaths, of which 15-20% were caused by lung cancer (2, 3) . In 2020, lung cancer occurred in 2.2 million people and resulted in 1.8 million deaths (4) which shows that most patients eventually die of the disease, the ratio of mortality to incidence being 0.87 (5) .  \nLung cancer, according to histological type, is divided into two broad categories: nonsmall cell lung carcinoma (NSCLC), the majority of cases, and small cell lung carcinoma (SCLC) . NSCLC is, in turn, classified as adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, which differ in therapy requirements and outcome (6) . These histological types differ in smoking and smoking cessation effects on lung cancer risk: in the Nurses’Health Study on 1,062 women with lung cancer, increasing smoking duration was associated with a higher increase in the risk of small cell and squamous cell carcinoma than other histological types of lung cancer, while smoking cessation decreased most strongly the risk of small cell carcinoma (7) . Lung adenocarcinoma has been further divided into the terminal  \nFrontiers in Immunology 01 [frontiersin.org](front","cbCail41GzMLsuXx","https://ap.wps.com/l/cbCail41GzMLsuXx","pdf",613555,12,"English","# Introduction\n## Lung cancer epidemiology and smoking risk\n## Histological types and smoking-related differences","[{\"question\":\"Why are smoking patterns closely linked to lung cancer epidemiology?\",\"answer\":\"Smoking is a major lung cancer risk factor, so geographic mortality trends follow historical cigarette smoking patterns, with changes across generations and countries.\"},{\"question\":\"How does lung cancer differ between smokers and never-smokers?\",\"answer\":\"Differences are reported across histological types, environmental risk factors, and genetic features, including gene expression, germ-line polymorphisms, and gene mutations, as well as ethnic and sex/gender differences.\"},{\"question\":\"What histological categories of lung cancer are discussed?\",\"answer\":\"The text divides lung cancer into non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC), and further describes NSCLC subtypes such as adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.\"}]","Genetic differences between smokers and never-smokers with lung cancer - review | PDF"]