Non-small cell lung cancer

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, EGFR 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. Mutations or overexpression of 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.

Cancer

K-ras (mutation) [HSA:3845] [KO:K07827]
EGFR (mutation) [HSA:1956] [KO:K04361]
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:238] [KO:K05119]
CD74-ROS1,SLC34A2-ROS1 (translocation) [HSA:6098] [KO:K05088]

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.

Methotrexate sodium [DR:D02115]
Pemetrexed sodium hydrate [DR:D06503]
Gemcitabine hydrochloride [DR:D01155]
Vinorelbine tartrate [DR:D01935]
Paclitaxel [DR:D00491]
Docetaxel [DR:D07866]
Docetaxel [DR:D02165]
Bevacizumab [DR:D06409]
Nivolumab [DR:D10316]
Pembrolizumab [DR:D10574]
Ramucirumab [DR:D09371]
Necitumumab [DR:D10018]
Durvalumab [DR:D10808]
Atezolizumab [DR:D10773]
Gefitinib [DR:D01977] (EGFR mutation positive)
Erlotinib hydrochloride [DR:D04023] (EGFR mutation positive)
Afatinib dimaleate [DR:D09733] (EGFR mutation positive)
Crizotinib [DR:D09731] (ALK or ROS1-positive)
Trametinib dimethyl sulfoxide [DR:D10176] (BRAF mutaion positive)
Ceritinib [DR:D10551] (ALK positive)
Osimertinib mesylate [DR:D10766] (EGFR mutation positive)
Alectinib hydrochloride [DR:D10450] (ALK positive)
Brigatinib [DR:D10866] (ALK positive)
Dacomitinib [DR:D10514] (EGFR mutation positive)

ICD-O: 8140/3, Tumor type: Adenocarcinoma
ICD-O: 8070/3, Tumor type: Squamous cell carcinoma

PMID:12741677 (tumor type)

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PMID:12711111 (tumor type)

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PMID:12407699

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PMID:16112428

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PMID:15769940

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PMID:17625570

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Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.

Nature 448:561-6 (2007)
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PMID:19406209

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Translocations in epithelial cancers.

Biochim Biophys Acta 1796:201-15 (2009)
DOI:10.1016/j.bbcan.2009.04.005

PMID:21850578

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Molecular oncology of lung cancer.

Gen Thorac Cardiovasc Surg 59:527-37 (2011)
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PMID:23733083

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Non-small cell lung cancer--genetic predictors.

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PMID:22327623

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RET, ROS1 and ALK fusions in lung cancer.

Nat Med 18:378-81 (2012)
DOI:10.1038/nm.2658

PMID:15322513 (carcinogen)

Boffetta P.

Epidemiology of environmental and occupational cancer.

Oncogene 23:6392-403 (2004)
DOI:10.1038/sj.onc.1207715

PMID:2831418 (carcinogen)

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PMID:14643412 (carcinogen)

Rossman TG.

Mechanism of arsenic carcinogenesis: an integrated approach.

Mutat Res 533:37-65 (2003)
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PMID:17244035 (carcinogen)

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Chronic arsenic poisoning: a global health issue -- a report of multiple primary cancers.

J Cutan Pathol 34:203-6 (2007)
DOI:10.1111/j.1600-0560.2006.00596.x

PMID:15660110 (carcinogen)

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Nature and nurture - lessons from chemical carcinogenesis.

Nat Rev Cancer 5:113-25 (2005)
DOI:10.1038/nrc1546

PMID:17375514 (carcinogen)

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Asbestos-related lung disease.

Am Fam Physician 75:683-8 (2007)

PMID:12082370 (carcinogen)

Gottschall EB.

Occupational and environmental thoracic malignancies.

J Thorac Imaging 17:189-97 (2002)

PMID:12556326 (carcinogen)

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Quantitative comparisons of cancer induction in humans by internally deposited radionuclides and external radiation.

Int J Radiat Biol 79:1-13 (2003)
DOI:10.1080/0955300021000038671

PMID:16411224 (carcinogen)

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Role of exposure to radon and silicosis on the cell type of lung carcinoma in German uranium miners.

Cancer 106:881-9 (2006)
DOI:10.1002/cncr.21677

PMID:11135223 (carcinogen)

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Histopathologic findings of lung carcinoma in German uranium miners.

Cancer 89:2613-21 (2000)
DOI:10.1002/1097-0142(20001215)89:12<2613::AID-CNCR14>3.0.CO;2-Y

PMID:11886955 (carcinogen)

Verma DK, Purdham JT, Roels HA.

Translating evidence about occupational conditions into strategies for prevention.

Occup Environ Med 59:205-13; quiz 214 (2002)
DOI:10.1136/oem.59.3.156

PMID:9358915 (carcinogen)

Honma K, Chiyotani K, Kimura K.

Silicosis, mixed dust pneumoconiosis, and lung cancer.

Am J Ind Med 32:595-9 (1997)
DOI:10.1002/(SICI)1097-0274(199712)32:6<595::AID-AJIM4>3.0.CO;2-P

PMID:15489140 (carcinogen)

Wogan GN, Hecht SS, Felton JS, Conney AH, Loeb LA.

Environmental and chemical carcinogenesis.

Semin Cancer Biol 14:473-86 (2004)
DOI:10.1016/j.semcancer.2004.06.010

PMID:15552776 (carcinogen)

Sasco AJ, Secretan MB, Straif K.

Tobacco smoking and cancer: a brief review of recent epidemiological evidence.

Lung Cancer 45 Suppl 2:S3-9 (2004)
DOI:10.1016/j.lungcan.2004.07.998

PMID:9498904 (carcinogen)

Boffetta P, Jourenkova N, Gustavsson P.

Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons.

Cancer Causes Control 8:444-72 (1997)

PMID:17530489 (carcinogen)

Abnet CC.

Carcinogenic food contaminants.

Cancer Invest 25:189-96 (2007)
DOI:10.1080/07357900701208733

PMID:17589590 (carcinogen)

Zhang JJ, Smith KR.

Household air pollution from coal and biomass fuels in china: measurements, health impacts, and interventions.

Environ Health Perspect 115:848-55 (2007)
DOI:10.1289/ehp.9479

PMID:17882278 (carcinogen)

Sun S, Schiller JH, Gazdar AF.

Lung cancer in never smokers--a different disease.

Nat Rev Cancer 7:778-90 (2007)
DOI:10.1038/nrc2190

PMID:10723042 (carcinogen)

Stern FB, Ruder AM, Chen G.

Proportionate mortality among unionized roofers and waterproofers.

Am J Ind Med 37:478-92 (2000)
DOI:10.1002/(SICI)1097-0274(200005)37:5<478::AID-AJIM4>3.0.CO;2-8

PMID:17032693 (carcinogen)

Hsu YM, Wu CY, Lundgren DA, Birky BK.

Size-resolved sulfuric acid mist concentrations at phosphate fertilizer manufacturing facilities in Florida.

Ann Occup Hyg 51:81-9 (2007)
DOI:10.1093/annhyg/mel066

PMID:9498905 (carcinogen)

Blair A, Kazerouni N.

Reactive chemicals and cancer.

Cancer Causes Control 8:473-90 (1997)

PMID:15070562 (carcinogen)

Berrington de Gonzalez A, Darby S.

Risk of cancer from diagnostic X-rays: estimates for the UK and 14 other countries.

Lancet 363:345-51 (2004)
DOI:10.1016/S0140-6736(04)15433-0