KEGG   DISEASE: H00014Help
Entry
H00014                      Disease                                

Name
Non-small cell lung cancer
Description
Lung cancer is a leading cause of cancer death among men and women in industrialized countries. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer and represents a heterogeneous group of cancers, consisting mainly of squamous cell (SCC), adeno (AC) and large-cell carcinoma. Molecular mechanisms altered in NSCLC include activation of oncogenes, such as K-RAS, c-erbB-2 and EML4-ALK, and inactivation of tumorsuppressor genes, such as p53, p16INK4a, RAR-beta, and RASSF1. Point mutations within the K-RAS gene inactivate GTPase activity and the p21-RAS protein continuously transmits growth signals to the nucleus. Overexpression of c-erbB-2 or EGFR leads to a proliferative advantage. EML4-ALK fusion leads to constitutive ALK activation, which causes cell proliferation, invasion, and inhibition of apoptosis. Inactivating mutation of p53 can lead to more rapid proliferation and reduced apoptosis. The protein encoded by the p16INK4a  inhibits formation of CDK-cyclin-D complexes by competitive binding of CDK4 and CDK6. Loss of p16INK4a expression is a common feature of NSCLC. RAR-beta is a nuclear receptor that bears vitamin-A-dependent transcriptional activity. RASSF1A is able to form heterodimers with Nore-1, an RAS effector.Therefore loss of RASSF1A might shift the balance of RAS activity towards a growth-promoting effect.
Category
Cancer
BRITE hierarchy
Pathway
Non-small cell lung cancer
MicroRNAs in cancer
Gene
K-ras (mutation) [HSA:3845] [KO:K07827]
RAR-beta (promoter hypermethylation) [HSA:5915] [KO:K08528]
FHIT (mutation) [HSA:2272] [KO:K01522]
RASSF1 (promoter hypermethylation) [HSA:11186] [KO:K09850]
p16/INK4A (mutation) [HSA:1029] [KO:K06621]
p53 (mutation/deletion) [HSA:7157] [KO:K04451]
EML4-ALK (translocation) [HSA:27436 238] [KO:K15420 K05119]
TFG-ALK (translocation) [HSA:10342 238] [KO:K09292 K05119]
SLC34A2-ROS1 (translocation) [HSA:10568 6098] [KO:K14683 K05088]
Carcinogen
Arsenic and arsenic compounds [CPD:C06269]
Arsenic in drinking-water
Asbestos [CPD:C16442]
Chromium[VI]
Mustard gas (Sulfur mustard)
Nickel compounds
Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes), as aerosols
Radon-222 and its decay products
Silica, crystalline (inhaled in the form of quartz orcristobalite from occupational sources) [CPD:C16459]
Tobacco smoking and tobacco smoke
*Aluminium production
*Benzo[a]pyrene [CPD:C07535]
*Cadmium and cadmium compounds
*Chimney sweeping
*Coal gasification
*Coal-tar pitches [CPD:C16451]
*Coal-tars [DR:D03573]
*Coke production
*Furniture and cabinet making
*Haematite mining (underground) with exposure to radon
*Household combustion of coal, indoor emissions from
*Involuntary smoking (exposure to secondhand or environmental tobacco smoke)
*Iron and steel founding
*Mineral oils, untreated and mildly treated
*Painter (occupational exposure as a)
*Paving and roofing with coal-tar pitch
*Shale-oils [CPD:C16458]
*Soots
*Strong-inorganic-acid mists containing sulfuric acid
*Talc containing asbestiform fibres
*2,3,7,8-Tetrachlorodibenzo-para-dioxin
*X- and gamma-radiation
*: Although this is a risk factor for lung cancer in general, the strength of association with different histological tumor types is not well understood.
Marker
CEA [HSA:1048]
CYFRA21-1 [HSA:3880]
Drug
Cisplatin [DR:D00275]
Carboplatin [DR:D01363]
Docetaxel [DR:D02165]
Gemcitabine [DR:D02368 D01155]
Gefitinib [DR:D01977]
Erlotinib [DR:D04023]
Etoposide [DR:D00125 D04107]
Vinblastine [DR:D01068]
Vinorelbine [DR:D01935]
Comment
ICD-O: 8140/3, Tumor type: Adenocarcinoma
ICD-O: 8070/3, Tumor type: Squamous cell carcinoma
Other DBs
ICD-10: 
MeSH: 
Reference
PMID:12741677 (tumor type)
  Authors
Yokota J, Nishioka M, Tani M, Kohno T.
  Title
Genetic alterations responsible for metastatic phenotypes of lung cancer cells.
  Journal
Clin Exp Metastasis 20:189-93 (2003)
Reference
PMID:12711111 (tumor type)
  Authors
Sanchez-Cespedes M.
  Title
Dissecting the genetic alterations involved in lung carcinogenesis.
  Journal
Lung Cancer 40:111-21 (2003)
Reference
PMID:12407699 (gene)
  Authors
Mitsuuchi Y, Testa JR.
  Title
Cytogenetics and molecular genetics of lung cancer.
  Journal
Am J Med Genet 115:183-8 (2002)
Reference
PMID:16112428 (gene)
  Authors
Panani AD, Roussos C.
  Title
Cytogenetic and molecular aspects of lung cancer.
  Journal
Cancer Lett 239:1-9 (2006)
Reference
PMID:15769940 (gene)
  Authors
Meuwissen R, Berns A.
  Title
Mouse models for human lung cancer.
  Journal
Genes Dev 19:643-64 (2005)
Reference
PMID:17625570 (gene)
  Authors
Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S, Watanabe H, Kurashina K, Hatanaka H, Bando M, Ohno S, Ishikawa Y, Aburatani H, Niki T, Sohara Y, Sugiyama Y, Mano H
  Title
Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.
  Journal
Nature 448:561-6 (2007)
Reference
PMID:19406209 (gene)
  Authors
Brenner JC, Chinnaiyan AM
  Title
Translocations in epithelial cancers.
  Journal
Biochim Biophys Acta 1796:201-15 (2009)
Reference
PMID:15322513 (carcinogen)
  Authors
Boffetta P.
  Title
Epidemiology of environmental and occupational cancer.
  Journal
Oncogene 23:6392-403 (2004)
Reference
PMID:2831418 (carcinogen)
  Authors
Adachi S, Takemoto K.
  Title
[Occupational lung cancer. A comparison between humans and experimental animals]
  Journal
Sangyo Igaku 29:345-57 (1987)
Reference
PMID:14643412 (carcinogen)
  Authors
Rossman TG.
  Title
Mechanism of arsenic carcinogenesis: an integrated approach.
  Journal
Mutat Res 533:37-65 (2003)
Reference
PMID:17244035 (carcinogen)
  Authors
Walvekar RR, Kane SV, Nadkarni MS, Bagwan IN, Chaukar DA, D'Cruz AK.
  Title
Chronic arsenic poisoning: a global health issue -- a report of multiple primary cancers.
  Journal
J Cutan Pathol 34:203-6 (2007)
Reference
PMID:15660110 (carcinogen)
  Authors
Luch A.
  Title
Nature and nurture - lessons from chemical carcinogenesis.
  Journal
Nat Rev Cancer 5:113-25 (2005)
Reference
PMID:17375514 (carcinogen)
  Authors
O'Reilly KM, Mclaughlin AM, Beckett WS, Sime PJ.
  Title
Asbestos-related lung disease.
  Journal
Am Fam Physician 75:683-8 (2007)
Reference
PMID:12082370 (carcinogen)
  Authors
Gottschall EB.
  Title
Occupational and environmental thoracic malignancies.
  Journal
J Thorac Imaging 17:189-97 (2002)
Reference
PMID:12556326 (carcinogen)
  Authors
Harrison JD, Muirhead CR.
  Title
Quantitative comparisons of cancer induction in humans by internally deposited radionuclides and external radiation.
  Journal
Int J Radiat Biol 79:1-13 (2003)
Reference
PMID:16411224 (carcinogen)
  Authors
Taeger D, Fritsch A, Wiethege T, Johnen G, Eisenmenger A, Wesch H, Ko Y, Stier S, Michael Muller K, Bruning T, Pesch B.
  Title
Role of exposure to radon and silicosis on the cell type of lung carcinoma in German uranium miners.
  Journal
Cancer 106:881-9 (2006)
Reference
PMID:11135223 (carcinogen)
  Authors
Kreuzer M, Muller KM, Brachner A, Gerken M, Grosche B, Wiethege T, Wichmann HE.
  Title
Histopathologic findings of lung carcinoma in German uranium miners.
  Journal
Cancer 89:2613-21 (2000)
Reference
PMID:11886955 (carcinogen)
  Authors
Verma DK, Purdham JT, Roels HA.
  Title
Translating evidence about occupational conditions into strategies for prevention.
  Journal
Occup Environ Med 59:205-13; quiz 214 (2002)
Reference
PMID:9358915 (carcinogen)
  Authors
Honma K, Chiyotani K, Kimura K.
  Title
Silicosis, mixed dust pneumoconiosis, and lung cancer.
  Journal
Am J Ind Med 32:595-9 (1997)
Reference
PMID:15489140 (carcinogen)
  Authors
Wogan GN, Hecht SS, Felton JS, Conney AH, Loeb LA.
  Title
Environmental and chemical carcinogenesis.
  Journal
Semin Cancer Biol 14:473-86 (2004)
Reference
PMID:15552776 (carcinogen)
  Authors
Sasco AJ, Secretan MB, Straif K.
  Title
Tobacco smoking and cancer: a brief review of recent epidemiological evidence.
  Journal
Lung Cancer 45 Suppl 2:S3-9 (2004)
Reference
PMID:9498904 (carcinogen)
  Authors
Boffetta P, Jourenkova N, Gustavsson P.
  Title
Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons.
  Journal
Cancer Causes Control 8:444-72 (1997)
Reference
PMID:17530489 (carcinogen)
  Authors
Abnet CC.
  Title
Carcinogenic food contaminants.
  Journal
Cancer Invest 25:189-96 (2007)
Reference
PMID:17589590 (carcinogen)
  Authors
Zhang JJ, Smith KR.
  Title
Household air pollution from coal and biomass fuels in china: measurements, health impacts, and interventions.
  Journal
Environ Health Perspect 115:848-55 (2007)
Reference
PMID:17882278 (carcinogen)
  Authors
Sun S, Schiller JH, Gazdar AF.
  Title
Lung cancer in never smokers--a different disease.
  Journal
Nat Rev Cancer 7:778-90 (2007)
Reference
PMID:10723042 (carcinogen)
  Authors
Stern FB, Ruder AM, Chen G.
  Title
Proportionate mortality among unionized roofers and waterproofers.
  Journal
Am J Ind Med 37:478-92 (2000)
Reference
PMID:17032693 (carcinogen)
  Authors
Hsu YM, Wu CY, Lundgren DA, Birky BK.
  Title
Size-resolved sulfuric acid mist concentrations at phosphate fertilizer manufacturing facilities in Florida.
  Journal
Ann Occup Hyg 51:81-9 (2007)
Reference
PMID:9498905 (carcinogen)
  Authors
Blair A, Kazerouni N.
  Title
Reactive chemicals and cancer.
  Journal
Cancer Causes Control 8:473-90 (1997)
Reference
PMID:15070562 (carcinogen)
  Authors
Berrington de Gonzalez A, Darby S.
  Title
Risk of cancer from diagnostic X-rays: estimates for the UK and 14 other countries.
  Journal
Lancet 363:345-51 (2004)
Reference
PMID:17534168 (marker)
  Authors
Greenberg AK, Lee MS.
  Title
Biomarkers for lung cancer: clinical uses.
  Journal
Curr Opin Pulm Med 13:249-55 (2007)
Reference
PMID:16033098 (marker)
  Authors
Molina R, Auge JM, Filella X, Vinolas N, Alicarte J, Domingo JM, Ballesta AM.
  Title
Pro-gastrin-releasing peptide (proGRP) in patients with benign and malignant diseases: comparison with CEA, SCC, CYFRA 21-1 and NSE in patients with lung cancer.
  Journal
Anticancer Res 25:1773-8 (2005)
Reference
PMID:17131623 (marker)
  Authors
Schneider J.
  Title
Tumor markers in detection of lung cancer.
  Journal
Adv Clin Chem 42:1-41 (2006)
Reference
(drug)
  Authors
McPhee SJ, Papadakis MA, Tierney LM (ed).
  Title
Current Medical Diagnosis & Treatment 2007, Forty-Sixth Edition
  Journal
The McGraw-Hill Companies, Inc. (2007)

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