Abstract
Lung cancer is the leading cause of cancer-related mortality in both men and women, with about 1.61 million new diagnoses and 1.38 million deaths worldwide in 2008. Non-small cell lung cancer (NSCLC), including squamous carcinoma, adenocarcinoma, and undifferentiated large cell carcinoma, accounts for more than 80 % of new lung cancer diagnoses. Unfortunately, at the time of diagnosis, the majority of patients have advanced disease, for which a systemic, palliative treatment is the primary therapeutic option. Considering that 47 % of all lung cancers are diagnosed in patients older than 70 years (14 % in patients older than 80 years), advanced NSCLC in elderly patients is an increasingly common problem, which the practitioner of oncology must face. The relationship between aging and cancer is not clear; considerable controversy surrounds the mechanisms that lead to increased incidence of cancer in the aged. It is worthy to note that frequencies of specific cancers are age-specific.
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Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics. CA Cancer J Clin. 2005;55:74–108.
Owonikoko TK, Ragin CC, Belani CP, et al. Lung cancer in elderly patients: an analysis of the surveillance, epidemiology, and end results database. J Clin Oncol. 2007;25:5570–7.
Wingo PA, Cardinez CJ, Landis SH, et al. Long term trends in cancer mortality in the United States. Cancer. 2003;97:3133–275.
Gridelli C, Perrone F, Monfardini S, et al. Lung cancer in the elderly. Eur J Cancer. 1997;33(14):2313–4.
Havlik RJ, Yancik R, Long S, et al. The National Institute on Aging and the National Cancer Institute SEER collaborative study on comorbidity and early diagnosis of cancer in the elderly. Cancer. 1994;74(Suppl):2101–6.
Dix D, Cohen P. On the role of aging in carcinogenesis. Anticancer Res. 1999;19:723–6.
Parkin DM, Bray FI, Devesa S. Cancer burden in the year 2000. The global picture. Eur J Cancer. 2001;37:S4–66.
Peto R, Roe FJC, Lee PN, Levy L, Clack J. Cancer and ageing in mice and men. Br J Cancer. 1975;32:411–26.
Peto R, Parish SE, Gray RG. There is no such thing as ageing, and cancer is not related to it. In: Likhachev A, Anisimov V, Montesano R, editors. Age-related factors in carcinogenesis, vol. 58. Lyon: IARC; 1985. p. 43–53.
Anisimov VN. Carcinogenesis and aging. Adv Cancer Res. 1983;40:265–324.
Anisimov VN. Carcinogenesis and aging, vol. 1, 2. Boca Raton: CRC Press; 1987.
Anisimov VN. Age-related mechanisms of susceptibility to carcinogenesis. Semin Oncol. 1989;16:10–9.
Dilman VM. Development, aging, and disease. A new rationale for and intervention strategy. Chur: Harwood Acad Publ; 1994.
Simpson AJG. A natural somatic mutation frequency and human carcinogenesis. Adv Cancer Res. 1997;71:209–40.
Anisimov VN. Age as a factor of risk in multistage carcinogenesis. In: Balducci L, Lyman GH, Ershler WB, editors. Comprehensive geriatric oncology. Amsterdam: Harwood Academic Publishers; 1998. p. 157–78.
DePinho RA. The age of cancer. Nature. 2000;408:248–54.
Fernandez-Pol JA, Douglas MG. Molecular interactions of cancer and age. Hematol Oncol Clin North Am. 2000;14:25–44.
Rubin H. Selected cell and selective microenvironment in neoplastic development. Cancer Res. 2001;61:799–807.
Campisi J. Aging and cancer: the double-edged sword or replicative senescence. J Am Geriatr Soc. 1997;45:1–6.
Campisi J. Cancer, aging, and cellular senescence. In Vivo. 2000;14:183–8.
Campisi J, Kirn S, Lim CS, Rubio M. Cellular senescence, cancer and aging: the telomere connection. Exp Gerontol. 2001;36:1619–37.
Krtolica A, Parincllo S, Lockett S, Desprez P-Y, Campisi J. Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging. Proc Natl Acad Sci USA. 2001;98:12072–7.
Rinehart CA, Torti VR. Aging and cancer: the role of stromal interactions with epithelial cells. Mol Carcinog. 1997;18:187–92.
Dakubo GD, Jakupciak JP, Birch-Machin MA, Parr RL. Clinical implications and utility of field cancerization. Cancer Cell Int. 2007;7:2.
Slaughter DP, Southwick HW, Smejkal W. Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer. 1953;6(5):963–8.
Steiling K, Ryan J, Brody JS, Spira A. The field of tissue injury in the lung and airway. Cancer Prev Res (Phila). 2008;1(6):396–403.
Wistuba II, Lam S, Behrens C, et al. Molecular damage in the bronchial epithelium of current and former smokers. J Natl Cancer Inst. 1997;89(18):1366–73.
Powell CA, Klares S, O’Connor G, Brody JS. Loss of heterozygosity in epithelial cells obtained by bronchial brushing: clinical utility in lung cancer. Clin Cancer Res. 1999;5(8):2025–34.
Bhutani M, Pathak AK, Fan YH, et al. Oral epithelium as a surrogate tissue for assessing smoking-induced molecular alterations in the lungs. Cancer Prev Res (Phila). 2008;1(1):39–44.
Sridhar S, Schembri F, Zeskind J, et al. Smoking-induced gene expression changes in the bronchial airway are reflected in nasal and buccal epithelium. BMC Genomics. 2008;9:259.
Auerbach O, Hammond EC, Kirman D, Garfinkel L. Effects of cigarette smoking on dogs, II: pulmonary neoplasms. Arch Environ Health. 1970;21(6):754–68.
Nelson MA, Wymer J, Clements Jr N. Detection of K-ras gene mutations in non-neoplastic lung tissue and lung cancers. Cancer Lett. 1996;103(1):115–21.
Tang X, Shigematsu H, Bekele BN, et al. EGFR tyrosine kinase domain mutations are detected in histologically normal respiratory epithelium in lung cancer patients. Cancer Res. 2005;65(17):7568–72.
Tang X, Varella-Garcia M, Xavier AC, et al. Epidermal growth factor receptor abnormalities in the pathogenesis and progression of lung adenocarcinomas. Cancer Prev Res (Phila). 2008;1(3):192–200.
Hackett NR, Heguy A, Harvey BG, et al. Variability of antioxidant-related gene expression in the airway epithelium of cigarette smokers. Am J Respir Cell Mol Biol. 2003;29(3 Pt 1):331–43.
Spira A, Beane J, Shah V, et al. Effects of cigarette smoke on the human airway epithelial cell transcriptome. Proc Natl Acad Sci USA. 2004;101(27):10143–8.
Spira A, Beane JE, Shah V, et al. Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer. Nat Med. 2007;13(3):361–6.
Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70.
Lindahl T. Instability and decay of the primary structure of DNA. Nature. 1993;362:709–15.
Pitot HC. The molecular biology of carcinogenesis. Cancer. 1993;72:962–70.
Vijg J. Somatic mutations and aging: a re-evaluation. Mutat Res. 2000;447:117–35.
Luzatto L. The mechanisms of neoplastic transformation. Eur J Cancer. 2001;37:S114–7.
Kinzler KW, Vogelstein B. Gatekeepers and caretakers. Nature. 1997;386:761–3.
Catania J, Fairweather DS. DNA methylation and cellular aging. Mutat Res. 1991;256:283–93.
Coller HA, Khrapko K, Bodyak ND, et al. High frequency of homoplasmic mitochondrial DNA mutations in human tumors can be explained without selection. Nat Genet. 2001;28:147–50.
Coller HA, Bodyak ND, Khrapko K. Frequent intracellular clonal expansions of somatic mtDNA mutations. Ann N Y Acad Sci. 2002;959:434–47.
Nekhaeva E, Bodyak ND, Kraytsberg Y, et al. Clonally expanded mtDNA point mutations are abundant in individual cells of human tissues. Proc Natl Acad Sci USA. 2002;99:5521–6.
Ambros V. MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing. Cell. 2003;113(6):673–6.
Vanio H, Magee PN, McGregor D, McMichael AJ, editors. Mechanisms of carcinogenesis in risk identification. IARC science publication number 116. Lyon: IARC;1992. p. 9–56.
Moolgavkar S, Krewski D, Zeise L, et al., editors. Quantitative estimation and prediction of human cancer risk, IARC science publication number 131. Lyon: IARC; 1999.
Simons JW. Genetic, epigenetic, dysgenetic and non-genetic mechanisms in tumorigenesis. II. Further delineation of the rate limiting step. Anticancer Res. 1999;19:4781–9.
Ponten J. Cell biology of precancer. Eur J Cancer. 2001;37:S97–113.
Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414:105–11.
Schlessinger D, Van Zant G. Does functional depletion of stem cells drive aging. Mech Ageing Dev. 2001;122:1537–53.
Aboseif S, El-Sakka A, Young P, Cunha G. Mesenchymal reprogramming of adult human epithelial differentiation. Differentiation. 1999;65:113–8.
Liotta LA, Kohn EC. The microenvironment of the tumor-host interface. Nature. 2001;411:375–9.
Anisimov VN, Zhukovskaya NV, Loktionov AS, et al. Influence of host age on lung colony forming capacity of injected rat rhabdomyosarcoma cells. Cancer Lett. 1988;40:77–82.
Anisimov VN, Zhukovskaya NV, Loktionov AS, et al. Host and donor age dependency of colony forming capacity of lung-affine rat rhabdomyosarcoma RA-2 cells. In: Abstract of the international conference on tumor micro environment: progression, therapy and prevention. Israel: Tiberias; 1995. p. 6.
Harman D. Free-radical theory of aging: increasing the functional life span. Ann N Y Acad Sci. 1994;717:257–66.
Harman DH. Extending functional life span. Exp Gerontol. 1998;33:95–112.
Hamilton ML, Van Remmen H, Drake JA, et al. Does oxidative damage to DNA increase with age. Proc Natl Acad Sci USA. 2001;98:10469–74.
Skulachev VP. The programmed death phenomena, aging, and the Samurai law of biology. Exp Gerontol. 2001;36:995–1024.
Kawanishi S, Hiraki Y, Oikawa S. Mechanism of guanine-specific DNA damage by oxidative stress and its role in carcinogenesis and aging. Mutat Res. 2001;488:65–76.
Salvioli S, Bonafe M, Capri M, Monti D, Fransceschi C. Mitochondria, aging and longevity–a new perspective. FEBS Lett. 2001;492:9–13.
von Zglinicki T, Burkle A, Kirkwood TBL. Stress, DNA damage and aging-an integrative approach. Exp Gerontol. 2001;36:1049–62.
Yu BP, editor. Free radicals in aging. Boca Raton: CRC Press; 1993.
Shigenaga MK, Hagen TV, Ames BN. Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci USA. 1994;91:10771–8.
Barja G. Endogenous oxidative stress: relation to aging, longevity and caloric restriction. Ageing Res Rev. 2002;1:397–411.
Du MQ, Carmichael PL, Phillips DH. Induction of activated mutations in the human c-Ha-ras proto-oncogene by oxygen free radicals. Mol Carcinog. 1994;11:170–5.
Ames BN, Shigenaga MB, Hagen TM. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA. 1993;90:7915–22.
Reiter RJ. Reactive oxygen species, DNA damage, and carcinogenesis: intervention with melatonin. In: Bartsch C, Bartsch H, Blask DE, Cardinali DP, Hrushesky WJM, Mecke D, editors. The pineal gland and cancer neuroimmunoendocrine mechanisms in malignancy. Berlin: Springer; 2001. p. 442–55.
Saretzki G, Sitte N, Merkel U, Wurm RE. Telomere shortening triggers a p53-dependent cell cycle arrest via accumulation of Grich single stranded DNA fragments. Oncogene. 1999;18:5148–58.
von Zglinicki T, Pilger R, Sitte N. Accumulation of single-strand breaks is the major cause of telomere shortening in human fibroblasts. Free Radic Biol Med. 2000;28:64–74.
Proctor CJ, Kikwood TBL. Modelling telomere shortening and the role of oxidative stress. Mech Ageing Dev. 2002;123:351–6.
Colotta F, Allavena P, Sica A, et al. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis. 2009;30(7):1073–81.
Brody JS, Spira A. State of the art: chronic obstructive pulmonary disease, inflammation, and lung cancer. Proc Am Thorac Soc. 2006;3(6):535–7.
Smith CJ, Perfetti TA, King JA. Perspectives on pulmonary inflammation and lung cancer risk in cigarette smokers. Inhal Toxicol. 2006;18(9):667–77.
Baratelli F, Lin Y, Zhu L, et al. Prostaglandin E2 induces FOXP3 gene expression and T regulatory cell function in human CD4þT cells. J Immunol. 2005;175(3):1483–90.
Gavin MA, Rasmussen JP, Fontenot JD, et al. Foxp3- dependent programme of regulatory T-cell differentiation. Nature. 2007;445(7129):771–5.
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Fasano, M., Cantile, F., Morgillo, F., Ciardiello, F. (2013). Basic Science of Lung Cancer in Older Patients. In: Gridelli, C., Audisio, R. (eds) Management of Lung Cancer in Older People. Springer, London. https://doi.org/10.1007/978-0-85729-793-8_1
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DOI: https://doi.org/10.1007/978-0-85729-793-8_1
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