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Pulmonary Malignancies (1): Lung Cancer—What Are the Roles of Genetic Factors in Lung Cancer Pathogenesis?

  • Naozumi Hashimoto
  • Mitsuo Sato
  • Yoshinori Hasegawa
Chapter
Part of the Respiratory Disease Series: Diagnostic Tools and Disease Managements book series (RDSDTDM)

Abstract

Carcinogenesis, including that of lung cancer, has been shown to be caused by the accumulation of genetic alterations. Some of the genetic changes are germline mutations, inherited gene alterations, and single-nucleotide polymorphisms. Germline mutations and inherited gene alterations are related to the development of familial lung cancer, and certain single-nucleotide polymorphisms are associated with an increase in the risk of lung cancer. Other factors associated with an increase in the risk of lung cancer include environmental and genetic interactions. The inhalation of a number of environmental carcinogenic agents, such as tobacco smoke, asbestos, or air pollutants, may lead to the induction of gene mutations, misreading in gene replication, or damage of DNA repair mechanisms. Multiple mechanisms for the acquisition of genetic predisposition to lung cancer have been intensively investigated, and further scientific knowledge would be valuable in the development of new therapeutic targets for treating lung cancer.

Keywords

Lung cancer Familial lung cancer Genetic factors Environmental factors 

References

  1. 1.
    Cancer statistics in Japan 2014. Foundation for Promotion of Cancer Research Source: estimated using the method by Wum LM et al., Estimating lifetime and age-conditional probabilities of developing cancer. Lifetime Data Anal. 1998;4:169–86.CrossRefGoogle Scholar
  2. 2.
    Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, Xie M, Zhang Q, McMichael JF, Wyczalkowski MA, Leiserson MD, Miller CA, Welch JS, Walter MJ, Wendl MC, Ley TJ, Wilson RK, Raphael BJ, Ding L. Mutational landscape and significance across 12 major cancer types. Nature. 2013;502(7471):333–9.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Vogelstein B, Fearon ER, Kern SE, Hamilton SR, Preisinger AC, Nakamura Y, White R. Allelotype of colorectal carcinomas. Science. 1989;244(4901):207–11.CrossRefPubMedGoogle Scholar
  4. 4.
    Wakai K, Inoue M, Mizoue T, Tanaka K, Tsuji I, Nagata C, Tsugane S, Research Group for the Development and Evaluation of Cancer Prevention Strategies in Japan. Tobacco smoking and lung cancer risk: an evaluation based on a systematic review of epidemiological evidence among the Japanese population. Jpn J Clin Oncol. 2006;36(5):309–24.CrossRefPubMedGoogle Scholar
  5. 5.
    IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Tobacco smoke and involuntary smoking. IARC Monogr Eval Carcinog Risks Hum. 2004;83:78.Google Scholar
  6. 6.
    Sato M, Shames DS, Gazdar AF, Minna JD. A translational view of the molecular pathogenesis of lung cancer. J Thorac Oncol. 2007;2:327–43.CrossRefPubMedGoogle Scholar
  7. 7.
    Larsen JE, Minna JD. Molecular biology of lung cancer: clinical implications. Clin Chest Med. 2011;32:703–40.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012;489:519–25.CrossRefGoogle Scholar
  9. 9.
    Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature. 2014;511:543–50.CrossRefGoogle Scholar
  10. 10.
    George J, Lim JS, Jang SJ, et al. Comprehensive genomic profiles of small cell lung cancer. Nature. 2015;524:47–53.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr, Kinzler KW. Cancer genome landscapes. Science. 2013;339:1546–58.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Takeuchi K, Soda M, Togashi Y, et al. RET, ROS1 and ALK fusions in lung cancer. Nat Med. 2012;18:378–81.CrossRefPubMedGoogle Scholar
  13. 13.
    Karachaliou N, Pilotto S, Lazzari C, Bria E, de Marinis F, Rosell R. Cellular and molecular biology of small cell lung cancer: an overview. Transl Lung Cancer Res. 2016;5:2–15.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Gao J, Aksoy BA, Dogrusoz U, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013;6:pl1.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Cerami E, Gao J, Dogrusoz U, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2:401–4.CrossRefPubMedGoogle Scholar
  16. 16.
    Rudin CM, Durinck S, Stawiski EW, et al. Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer. Nat Genet. 2012;44:1111–6.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Armitage P, Doll R. The age distribution of cancer and a multi-stage theory of carcinogenesis. Br J Cancer. 1954;8:1–12.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Sato M, Vaughan MB, Girard L, et al. Multiple oncogenic changes (K-RAS(V12), p53 knockdown, mutant EGFRs, p16 bypass, telomerase) are not sufficient to confer a full malignant phenotype on human bronchial epithelial cells. Cancer Res. 2006;66:2116–28.CrossRefPubMedGoogle Scholar
  19. 19.
    Sato M, Larsen JE, Lee W, et al. Human lung epithelial cells progressed to malignancy through specific oncogenic manipulations. Mol Cancer Res. 2013;11:638–50.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350:2129–39.CrossRefPubMedGoogle Scholar
  21. 21.
    Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304:1497–500.CrossRefPubMedGoogle Scholar
  22. 22.
    Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448:561–6.CrossRefPubMedGoogle Scholar
  23. 23.
    Dammann R, Li C, Yoon JH, Chin PL, Bates S, Pfeifer GP. Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3. Nat Genet. 2000;25:315–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Zochbauer-Muller S, Fong KM, Virmani AK, Geradts J, Gazdar AF, Minna JD. Aberrant promoter methylation of multiple genes in non-small cell lung cancers. Cancer Res. 2001;61:249–55.PubMedGoogle Scholar
  25. 25.
    Bass AJ, Watanabe H, Mermel CH, et al. SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas. Nat Genet. 2009;41:1238–42.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Weir BA, Woo MS, Getz G, et al. Characterizing the cancer genome in lung adenocarcinoma. Nature. 2007;450:893–8.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    de Bruin EC, McGranahan N, Mitter R, et al. Spatial and temporal diversity in genomic instability processes defines lung cancer evolution. Science. 2014;346:251–6.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Zhang J, Fujimoto J, Zhang J, et al. Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing. Science. 2014;346:256–9.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Burns MB, Temiz NA, Harris RS. Evidence for APOBEC3B mutagenesis in multiple human cancers. Nat Genet. 2013;45:977–83.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Li FP, Fraumeni JF. Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Ann Intern Med. 1969;71:747–52.CrossRefPubMedGoogle Scholar
  31. 31.
    Varley JM. Germline TP53 mutations and Li-Fraumeni syndrome. Hum Mutat. 2003;21:313–20.CrossRefPubMedGoogle Scholar
  32. 32.
    Lynch HT, Guirgis HA. Childhood cancer and the SBLA syndrome. Med Hypotheses. 1979;5:15–22.CrossRefPubMedGoogle Scholar
  33. 33.
    Kleihues P, Schäuble B, zur Hausen A, Estève J, Ohgaki H. Tumors associated with p53 germline mutations: a synopsis of 91 families. Am J Pathol. 1997;150(1):1–13.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Hwang SJ, Cheng LS, Lozano G, Amos CI, Gu X, Strong LC. Lung cancer risk in germline p53 mutation carriers: association between an inherited cancer predisposition, cigarette smoking, and cancer risk. Hum Genet. 2003;113(3):238–43.CrossRefPubMedGoogle Scholar
  35. 35.
    Bell DW, Gore I, Okimoto RA, Godin-Heymann N, Sordella R, Mulloy R, Sharma SV, Brannigan BW, Mohapatra G, Settleman J, Haber DA. Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR. Nat Genet. 2005;37(12):1315–6.CrossRefPubMedGoogle Scholar
  36. 36.
    Kobayashi S, Boggon TJ, Dayaram T, Jänne PA, Kocher O, Meyerson M, Johnson BE, Eck MJ, Tenen DG, Halmos B. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med. 2005;352(8):786–92.CrossRefPubMedGoogle Scholar
  37. 37.
    Genetic Epidemiology of Lung Cancer Consortium GWAS of Familial Lung Cancer. https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000629.v1.p1
  38. 38.
    Bailey-Wilson JE, Amos CI, Pinney SM, Petersen GM, de Andrade M, Wiest JS, Fain P, Schwartz AG, You M, Franklin W, Klein C, Gazdar A, Rothschild H, Mandal D, Coons T, Slusser J, Lee J, Gaba C, Kupert E, Perez A, Zhou X, Zeng D, Liu Q, Zhang Q, Seminara D, Minna J, Anderson MW. A major lung cancer susceptibility locus maps to chromosome 6q23-25. Am J Hum Genet. 2004;75(3):460–74.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Kachuri L, Amos CI, McKay JD, Johansson M, Vineis P, Bueno-de-Mesquita HB, Boutron-Ruault MC, Johansson M, Quirós JR, Sieri S, Travis RC, Weiderpass E, Le Marchand L, Henderson BE, Wilkens L, Goodman GE, Chen C, Doherty JA, Christiani DC, Wei Y, Su L, Tworoger S, Zhang X, Kraft P, Zaridze D, Field JK, Marcus MW, Davies MP, Hyde R, Caporaso NE, Landi MT, Severi G, Giles GG, Liu G, McLaughlin JR, Li Y, Xiao X, Fehringer G, Zong X, Denroche RE, Zuzarte PC, McPherson JD, Brennan P, Hung RJ. Fine mapping of chromosome 5p15.33 based on a targeted deep sequencing and high density genotyping identifies novel lung cancer susceptibility loci. Carcinogenesis. 2016;37(1):96–105.CrossRefPubMedGoogle Scholar
  40. 40.
    Yamamoto K, et al. A novel gene, CRR9, which was up-regulated in CDDP-resistant ovarian tumor cell line, was associated with apoptosis. Biochem Biophys Res Commun. 2001;280:1148–54.CrossRefPubMedGoogle Scholar
  41. 41.
    James MA, et al. CRR9/CLPTM1L regulates cell survival signaling and is required for Ras transformation and lung tumorigenesis. Cancer Res. 2014;74:1116–27.CrossRefPubMedGoogle Scholar
  42. 42.
    Sasaki T, Gan EC, Wakeham A, Kornbluth S, Mak TW, Okada H. HLA-B-associated transcript 3 (Bat3)/Scythe is essential for p300-mediated acetylation of p53. Genes Dev. 2007;21(7):848–61.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    You M, Wang D, Liu P, Vikis H, James M, Lu Y, Wang Y, Wang M, Chen Q, Jia D, Liu Y, Wen W, Yang P, Sun Z, Pinney SM, Zheng W, Shu XO, Long J, Gao YT, Xiang YB, Chow WH, Rothman N, Petersen GM, de Andrade M, Wu Y, Cunningham JM, Wiest JS, Fain PR, Schwartz AG, Girard L, Gazdar A, Gaba C, Rothschild H, Mandal D, Coons T, Lee J, Kupert E, Seminara D, Minna J, Bailey-Wilson JE, Amos CI, Anderson MW. Fine mapping of chromosome 6q23-25 region in familial lung cancer families reveals RGS17 as a likely candidate gene. Clin Cancer Res. 2009;15(8):2666–74.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Liu P, Vikis HG, Wang D, Lu Y, Wang Y, Schwartz AG, Pinney SM, Yang P, de Andrade M, Petersen GM, Wiest JS, Fain PR, Gazdar A, Gaba C, Rothschild H, Mandal D, Coons T, Lee J, Kupert E, Seminara D, Minna J, Bailey-Wilson JE, Wu X, Spitz MR, Eisen T, Houlston RS, Amos CI, Anderson MW, You M. Familial aggregation of common sequence variants on 15q24-25.1 in lung cancer. J Natl Cancer Inst. 2008;100(18):1326–30.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Liu Y, Liu P, Wen W, James MA, Wang Y, Bailey-Wilson JE, Amos CI, Pinney SM, Yang P, de Andrade M, Petersen GM, Wiest JS, Fain PR, Schwartz AG, Gazdar A, Gaba C, Rothschild H, Mandal D, Kupert E, Lee J, Seminara D, Minna J, Anderson MW, You M. Haplotype and cell proliferation analyses of candidate lung cancer susceptibility genes on chromosome 15q24-25.1. Cancer Res. 2009;69(19):7844–50.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    LaVaute T, Smith S, Cooperman S, Iwai K, Land W, Meyron-Holtz E, Drake SK, Miller G, Abu-Asab M, Tsokos M, Switzer R III, Grinberg A, Love P, Tresser N, Rouault TA. Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice. Nat Genet. 2001;27(2):209–14.CrossRefPubMedGoogle Scholar
  47. 47.
    Davoli R, Fontanesi L, Russo V, Cepica S, Musilová P, Stratil A, Rubes J. The porcine proteasome subunit A4 (PSMA4) gene: isolation of a partial cDNA, linkage and physical mapping. Anim Genet. 1998;29(5):385–8.CrossRefPubMedGoogle Scholar
  48. 48.
    Nandi D, Woodward E, Ginsburg DB, Monaco JJ. Intermediates in the formation of mouse 20S proteasomes: implications for the assembly of precursor beta subunits. EMBO J. 1997;16(17):5363–75.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Hung RJ, McKay JD, Gaborieau V, Boffetta P, et al. A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature. 2008;452(7187):633–7.CrossRefPubMedGoogle Scholar
  50. 50.
    Wang JC, Cruchaga C, Saccone NL, et al. Risk for nicotine dependence and lung cancer is conferred by mRNA expression levels and amino acid change in CHRNA5. Hum Mol Genet. 2009;18(16):3125–35.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Schottenfeld D. The etiology and epidemiology of lung cancer. In: Pass HI, et al., editors. Principles and practice of lung cancer. Philadelphia: Lippincott Williams & Wilkins; 2010. p. 3–22.Google Scholar
  52. 52.
    Weinberg RA. Cell genomes are under occasional attack from exogenous mutagens and their metabolites. The biology of cancer. 2nd ed. New York: Garland Science; 2014. p. 527–35.Google Scholar
  53. 53.
    Kazma R, Babron MC, Gaborieau V, Génin E, Brennan P, Hung RJ, McLaughlin JR, Krokan HE, Elvestad MB, Skorpen F, Anderssen E, Vooder T, Välk K, Metspalu A, Field JK, Lathrop M, Sarasin A, Benhamou S. ILCCO consortium. Lung cancer and DNA repair genes: multilevel association analysis from the International Lung Cancer Consortium. Carcinogenesis. 2012;33(5):1059–64.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Agundez JA. Cytochrome P450 gene polymorphism and cancer. Curr Drug Metab. 2004;5(3):211–24.CrossRefPubMedGoogle Scholar
  55. 55.
    Nelson HH, Christiani DC, Wiencke JK, Mark EJ, Wain JC, Kelsey KT. K-ras mutation and occupational asbestos exposure in lung adenocarcinoma: asbestos-related cancer without asbestosis. Cancer Res. 1999;59(18):4570–3.PubMedGoogle Scholar
  56. 56.
    Panduri V, Surapureddi S, Soberanes S, Weitzman SA, Chandel N, Kamp DW. P53 mediates amosite asbestos-induced alveolar epithelial cell mitochondria-regulated apoptosis. Am J Respir Cell Mol Biol. 2006;34(4):443–52.CrossRefPubMedGoogle Scholar
  57. 57.
    Mitsudomi T, Kosaka T, Endoh H, et al. Mutations of the epidermal growth factor receptor gene predict prolonged survival after gefitinib treatment in patients with non-small-cell lung cancer with postoperative recurrence. J Clin Oncol. 2005;23:2513–20.CrossRefPubMedGoogle Scholar
  58. 58.
    Greenman C, Stephens P, Smith R, et al. Patterns of somatic mutation in human cancer genomes. Nature. 2007;446:153–8.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Ding L, Getz G, Wheeler DA, et al. Somatic mutations affect key pathways in lung adenocarcinoma. Nature. 2008;455:1069–75.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140:883–99.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    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;24:2371–6.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Shiraishi K, Kunitoh H, Daigo Y, et al. A genome-wide association study identifies two new susceptibility loci for lung adenocarcinoma in the Japanese population. Nat Genet. 2012;44:900–3.CrossRefPubMedGoogle Scholar
  63. 63.
    Shiraishi K, Okada Y, Takahashi A, et al. Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma. Nat Commun. 2016;7:12451.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Naozumi Hashimoto
    • 1
  • Mitsuo Sato
    • 1
  • Yoshinori Hasegawa
    • 1
  1. 1.Department of Respiratory MedicineNagoya University Graduate School of MedicineNagoyaJapan

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