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Published in: Cancer Cell International 1/2010

Open Access 01-12-2010 | Hypothesis

From 'omics' to complex disease: a systems biology approach to gene-environment interactions in cancer

Author: Sarah S Knox

Published in: Cancer Cell International | Issue 1/2010

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Abstract

Background

Cancer is a complex disease that involves a sequence of gene-environment interactions in a progressive process that cannot occur without dysfunction in multiple systems, including DNA repair, apoptotic and immune functions. Epigenetic mechanisms, responding to numerous internal and external cues in a dynamic ongoing exchange, play a key role in mediating environmental influences on gene expression and tumor development.

Hypothesis

The hypothesis put forth in this paper addresses the limited success of treatment outcomes in clinical oncology. It states that improvement in treatment efficacy requires a new paradigm that focuses on reversing systemic dysfunction and tailoring treatments to specific stages in the process. It requires moving from a reductionist framework of seeking to destroy aberrant cells and pathways to a transdisciplinary systems biology approach aimed at reversing multiple levels of dysfunction.

Conclusion

Because there are many biological pathways and multiple epigenetic influences working simultaneously in the expression of cancer phenotypes, studying individual components in isolation does not allow an adequate understanding of phenotypic expression. A systems biology approach using new modeling techniques and nonlinear mathematics is needed to investigate gene-environment interactions and improve treatment efficacy. A broader array of study designs will also be required, including prospective molecular epidemiology, immune competent animal models and in vitro/in vivo translational research that more accurately reflects the complex process of tumor initiation and progression.
Literature
1.
go back to reference Pedersen NL: The nature and nurture of personality. Personality Psychology in Europe. Edited by: De Raad B, Hofstee WKB, Van Heck GL. 1994, Tilburg: Tilburg University Press, 110-132. Pedersen NL: The nature and nurture of personality. Personality Psychology in Europe. Edited by: De Raad B, Hofstee WKB, Van Heck GL. 1994, Tilburg: Tilburg University Press, 110-132.
4.
go back to reference Riley T, Sontag E, Chen P, Levine A: Transcriptional control of human p53-regulated genes. Nature Reviews Molecular Cell Biology. 2008, 9 (5): 402-412. 10.1038/nrm2395.CrossRefPubMed Riley T, Sontag E, Chen P, Levine A: Transcriptional control of human p53-regulated genes. Nature Reviews Molecular Cell Biology. 2008, 9 (5): 402-412. 10.1038/nrm2395.CrossRefPubMed
5.
go back to reference Musani S, Shriner D, Liu N, Feng R, Coffey C, Yi N, Tiwari H, Allison D: Detection of gene× gene interactions in genome-wide association studies of human population data. Hum Hered. 2007, 63 (2): 67-84. 10.1159/000099179.CrossRefPubMed Musani S, Shriner D, Liu N, Feng R, Coffey C, Yi N, Tiwari H, Allison D: Detection of gene× gene interactions in genome-wide association studies of human population data. Hum Hered. 2007, 63 (2): 67-84. 10.1159/000099179.CrossRefPubMed
6.
go back to reference Gardner M, Bertranpetit J, Comas D: Worldwide genetic variation in dopamine and serotonin pathway genes: implications for association studies. American journal of medical genetics Part B, Neuropsychiatric genetics: the official publication of the International Society of Psychiatric Genetics. 2008, 147 (7): 1070. Gardner M, Bertranpetit J, Comas D: Worldwide genetic variation in dopamine and serotonin pathway genes: implications for association studies. American journal of medical genetics Part B, Neuropsychiatric genetics: the official publication of the International Society of Psychiatric Genetics. 2008, 147 (7): 1070.
7.
go back to reference Testa B, Kier L, Carrupt P: A systems approach to molecular structure, intermolecular recognition, and emergence-dissolvence in medicinal research. Medicinal Research Reviews. 1997, 17 (4): 10.1002/(SICI)1098-1128(199707)17:4<303::AID-MED1>3.0.CO;2-#. Testa B, Kier L, Carrupt P: A systems approach to molecular structure, intermolecular recognition, and emergence-dissolvence in medicinal research. Medicinal Research Reviews. 1997, 17 (4): 10.1002/(SICI)1098-1128(199707)17:4<303::AID-MED1>3.0.CO;2-#.
8.
go back to reference Alberghina L, Höfer T, Vanoni M: Molecular networks and system-level properties. Journal of Biotechnology. 2009, 144 (3): 224-33. 10.1016/j.jbiotec.2009.07.009.CrossRefPubMed Alberghina L, Höfer T, Vanoni M: Molecular networks and system-level properties. Journal of Biotechnology. 2009, 144 (3): 224-33. 10.1016/j.jbiotec.2009.07.009.CrossRefPubMed
9.
go back to reference Poirier MG, Oh E, Tims HS, Widom J: Dynamics and function of compact nucleosome arrays. Nature Structural & Molecular Biology. 2009, 16 (9): 938-944. 10.1038/nsmb.1650.CrossRef Poirier MG, Oh E, Tims HS, Widom J: Dynamics and function of compact nucleosome arrays. Nature Structural & Molecular Biology. 2009, 16 (9): 938-944. 10.1038/nsmb.1650.CrossRef
10.
go back to reference Agutter P, Wheatley D: About Life: Concepts in Modern Biology. 2007, Dordrecht, The Netherlands: Springer Agutter P, Wheatley D: About Life: Concepts in Modern Biology. 2007, Dordrecht, The Netherlands: Springer
11.
go back to reference Jirtle R, Skinner M: Environmental epigenomics and disease susceptibility. Nature reviews genetics. 2007, 8 (4): 253-262. 10.1038/nrg2045.CrossRefPubMed Jirtle R, Skinner M: Environmental epigenomics and disease susceptibility. Nature reviews genetics. 2007, 8 (4): 253-262. 10.1038/nrg2045.CrossRefPubMed
12.
go back to reference Voss A, Schroeder R, Truebner S, Goernig M, Figulla H, Schirdewan A: Comparison of nonlinear methods symbolic dynamics, detrended fluctuation, and Poincare plot analysis in risk stratification in patients with dilated cardiomyopathy. Chaos: An Interdisciplinary Journal of Nonlinear Science. 2007, 17: 015120-10.1063/1.2404633.CrossRef Voss A, Schroeder R, Truebner S, Goernig M, Figulla H, Schirdewan A: Comparison of nonlinear methods symbolic dynamics, detrended fluctuation, and Poincare plot analysis in risk stratification in patients with dilated cardiomyopathy. Chaos: An Interdisciplinary Journal of Nonlinear Science. 2007, 17: 015120-10.1063/1.2404633.CrossRef
13.
go back to reference Peng C, Buldyrev S, Hausdorff J, Havlin S, Mietus J, Simons M, Stanley H, Goldberger A: Non-equilibrium dynamics as an indispensable characteristic of a healthy biological system. Integrative Psychological and Behavioral Science. 1994, 29 (3): 283-293. 10.1007/BF02691332.CrossRef Peng C, Buldyrev S, Hausdorff J, Havlin S, Mietus J, Simons M, Stanley H, Goldberger A: Non-equilibrium dynamics as an indispensable characteristic of a healthy biological system. Integrative Psychological and Behavioral Science. 1994, 29 (3): 283-293. 10.1007/BF02691332.CrossRef
14.
go back to reference Stanley H, Buldyrev S, Goldberger A, Havlin S, Peng C, Simons M: Scaling features of noncoding DNA. Physica A. 1999, 273 (1-2): 1-18. 10.1016/S0378-4371(99)00407-0.CrossRefPubMed Stanley H, Buldyrev S, Goldberger A, Havlin S, Peng C, Simons M: Scaling features of noncoding DNA. Physica A. 1999, 273 (1-2): 1-18. 10.1016/S0378-4371(99)00407-0.CrossRefPubMed
15.
go back to reference Goldberger A, Amaral L, Hausdorff J, Ivanov P, Peng C, Stanley H: Fractal dynamics in physiology: alterations with disease and aging. National Acad Sciences. 2002, 99: 2466-2472. 10.1073/pnas.012579499.CrossRef Goldberger A, Amaral L, Hausdorff J, Ivanov P, Peng C, Stanley H: Fractal dynamics in physiology: alterations with disease and aging. National Acad Sciences. 2002, 99: 2466-2472. 10.1073/pnas.012579499.CrossRef
16.
go back to reference Scheffer M, Bascompte J, Brock WA, Brovkin V, Carpenter SR, Dakos V, Held H, van Nes EH, Rietkerk M, Sugihara G: Early-warning signals for critical transitions. Nature. 2009, 461 (7260): 53. 10.1038/nature08227. Scheffer M, Bascompte J, Brock WA, Brovkin V, Carpenter SR, Dakos V, Held H, van Nes EH, Rietkerk M, Sugihara G: Early-warning signals for critical transitions. Nature. 2009, 461 (7260): 53. 10.1038/nature08227.
17.
go back to reference Kirschner M: The meaning of systems biology. Cell. 2005, 121 (4): 503-504. 10.1016/j.cell.2005.05.005.CrossRefPubMed Kirschner M: The meaning of systems biology. Cell. 2005, 121 (4): 503-504. 10.1016/j.cell.2005.05.005.CrossRefPubMed
18.
go back to reference Ahn AC, Tewari M, Chi-Sang P, Phillips RS: The Limits of Reductionism in Medicine: Could Systems Biology Offer an Alternative?. PLoS Medicine. 2006, 3 (5): e208-0713. 10.1371/journal.pmed.0030208.PubMedCentralCrossRefPubMed Ahn AC, Tewari M, Chi-Sang P, Phillips RS: The Limits of Reductionism in Medicine: Could Systems Biology Offer an Alternative?. PLoS Medicine. 2006, 3 (5): e208-0713. 10.1371/journal.pmed.0030208.PubMedCentralCrossRefPubMed
19.
go back to reference Grigorov M: Global dynamics of biological systems from time-resolved omics experiments. 2006, Oxford Univ Press, 22: 1424-1430. Grigorov M: Global dynamics of biological systems from time-resolved omics experiments. 2006, Oxford Univ Press, 22: 1424-1430.
20.
go back to reference Dollery CKR, Challis R, Delpy D, Edwards D, Henney A, Kirkwood T, Noble D, Rowland M, Tarassenko L, Williams D, Smith L: Systems biology: A vision for engineering and medicine. A Report from the Academy of Medical Sciences and the Royal Academy of Engineering. 2007 Dollery CKR, Challis R, Delpy D, Edwards D, Henney A, Kirkwood T, Noble D, Rowland M, Tarassenko L, Williams D, Smith L: Systems biology: A vision for engineering and medicine. A Report from the Academy of Medical Sciences and the Royal Academy of Engineering. 2007
21.
go back to reference Vera J, Wolkenhauer O: A systems biology approach to understand functional activity of cell communications systems. Methods in Cell Biology. 2008, 90: 399-415. full_text.CrossRefPubMed Vera J, Wolkenhauer O: A systems biology approach to understand functional activity of cell communications systems. Methods in Cell Biology. 2008, 90: 399-415. full_text.CrossRefPubMed
22.
go back to reference Kamb A, Wee S, Lengauer C: Why is cancer drug discovery so difficult?. Nature Reviews Drug Discovery. 2006, 6 (2): 115-120. 10.1038/nrd2155.CrossRefPubMed Kamb A, Wee S, Lengauer C: Why is cancer drug discovery so difficult?. Nature Reviews Drug Discovery. 2006, 6 (2): 115-120. 10.1038/nrd2155.CrossRefPubMed
23.
go back to reference Schipper H, Goh C, Wang T: Shifting the cancer paradigm: must we kill to cure?. Journal of Clinical Oncology. 1995, 13 (4): 801-PubMed Schipper H, Goh C, Wang T: Shifting the cancer paradigm: must we kill to cure?. Journal of Clinical Oncology. 1995, 13 (4): 801-PubMed
24.
25.
go back to reference Hoeijmakers J: DNA Damage, Aging, and Cancer. New England Journal of Medicine. 2009, 361 (15): 1475-10.1056/NEJMra0804615.CrossRefPubMed Hoeijmakers J: DNA Damage, Aging, and Cancer. New England Journal of Medicine. 2009, 361 (15): 1475-10.1056/NEJMra0804615.CrossRefPubMed
26.
go back to reference Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ, Schreiber RD: IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature. 2001, 410 (6832): 1107-10.1038/35074122.CrossRefPubMed Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ, Schreiber RD: IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature. 2001, 410 (6832): 1107-10.1038/35074122.CrossRefPubMed
27.
go back to reference Jeong H, Tombor B, Albert R, Oltvai Z, Barabasi A: The large-scale organization of metabolic networks. Nature. 2000, 407 (6804): 651-654. 10.1038/35036627.CrossRefPubMed Jeong H, Tombor B, Albert R, Oltvai Z, Barabasi A: The large-scale organization of metabolic networks. Nature. 2000, 407 (6804): 651-654. 10.1038/35036627.CrossRefPubMed
28.
go back to reference Chauvet G: Hierarchical functional organization of formal biological systems: A dynamical approach. I. The increase of complexity by self-association increases the domain of stability of a biological system. Philosophical Transactions: Biological Sciences. 1993, 339 (1290): 425-444. 10.1098/rstb.1993.0040.CrossRef Chauvet G: Hierarchical functional organization of formal biological systems: A dynamical approach. I. The increase of complexity by self-association increases the domain of stability of a biological system. Philosophical Transactions: Biological Sciences. 1993, 339 (1290): 425-444. 10.1098/rstb.1993.0040.CrossRef
29.
go back to reference Callinan PA, Feinberg AP: The emerging science of epigenomics. Human Molecular Genetics. 2006, 15 (Spec No 1): R95-101. 10.1093/hmg/ddl095.CrossRefPubMed Callinan PA, Feinberg AP: The emerging science of epigenomics. Human Molecular Genetics. 2006, 15 (Spec No 1): R95-101. 10.1093/hmg/ddl095.CrossRefPubMed
30.
go back to reference Baylin SB, Chen WY: Aberrant Gene Silencing in Tumor Progression: Implications for Control of Cancer. Cold Spring Harbor Symposia on Quantitative Biology. 2005, 70: 427-433. 10.1101/sqb.2005.70.010.CrossRefPubMed Baylin SB, Chen WY: Aberrant Gene Silencing in Tumor Progression: Implications for Control of Cancer. Cold Spring Harbor Symposia on Quantitative Biology. 2005, 70: 427-433. 10.1101/sqb.2005.70.010.CrossRefPubMed
31.
go back to reference Jones P, Baylin S: The fundamental role of epigenetic events in cancer. Nature reviews genetics. 2002, 3 (6): 415-428.PubMed Jones P, Baylin S: The fundamental role of epigenetic events in cancer. Nature reviews genetics. 2002, 3 (6): 415-428.PubMed
33.
go back to reference Feinberg A, Ohlsson R, Henikoff S: The epigenetic progenitor origin of human cancer. Nature reviews genetics. 2006, 7 (1): 21-33. 10.1038/nrg1748.CrossRefPubMed Feinberg A, Ohlsson R, Henikoff S: The epigenetic progenitor origin of human cancer. Nature reviews genetics. 2006, 7 (1): 21-33. 10.1038/nrg1748.CrossRefPubMed
34.
go back to reference Bjornsson HT, Daniele Fallin M, Feinberg AP: An integrated epigenetic and genetic approach to common human disease. Trends in Genetics. 2004, 20 (8): 350-358. 10.1016/j.tig.2004.06.009.CrossRefPubMed Bjornsson HT, Daniele Fallin M, Feinberg AP: An integrated epigenetic and genetic approach to common human disease. Trends in Genetics. 2004, 20 (8): 350-358. 10.1016/j.tig.2004.06.009.CrossRefPubMed
35.
go back to reference Burns D: Tobacco-related diseases. 2003, Elsevier, 244-249. Burns D: Tobacco-related diseases. 2003, Elsevier, 244-249.
36.
go back to reference Gan Q, Smith K, Hammond S, Hu T: Disease burden of adult lung cancer and ischaemic heart disease from passive tobacco smoking in China. British Medical Journal. 2007, 16 (6): 417- Gan Q, Smith K, Hammond S, Hu T: Disease burden of adult lung cancer and ischaemic heart disease from passive tobacco smoking in China. British Medical Journal. 2007, 16 (6): 417-
37.
go back to reference Alberg AJ, Samet JM: Epidemiology of Lung Cancer. CHEST. 2003, 123: 21S-10.1378/chest.123.1_suppl.21S.CrossRefPubMed Alberg AJ, Samet JM: Epidemiology of Lung Cancer. CHEST. 2003, 123: 21S-10.1378/chest.123.1_suppl.21S.CrossRefPubMed
38.
go back to reference Mattson M, Pollack E, Cullen J: What are the odds that smoking will kill you?. Am Public Health Assoc. 1987, 77: 425-431. 10.2105/AJPH.77.4.425.CrossRef Mattson M, Pollack E, Cullen J: What are the odds that smoking will kill you?. Am Public Health Assoc. 1987, 77: 425-431. 10.2105/AJPH.77.4.425.CrossRef
39.
go back to reference Subramanian J, Govindan R: Lung cancer in never smokers: a review. Journal of Clinical Oncology. 2007, 25 (5): 561-10.1200/JCO.2006.06.8015.CrossRefPubMed Subramanian J, Govindan R: Lung cancer in never smokers: a review. Journal of Clinical Oncology. 2007, 25 (5): 561-10.1200/JCO.2006.06.8015.CrossRefPubMed
40.
go back to reference Parkin D, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA: a cancer journal for clinicians. 2005, 55 (2): 74-108. 10.3322/canjclin.55.2.74. Parkin D, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA: a cancer journal for clinicians. 2005, 55 (2): 74-108. 10.3322/canjclin.55.2.74.
41.
go back to reference Sellers T, Elston R, Stewart C, Rothschild H, Vogler G: Familial risk of cancer among randomly selected cancer probands. Genetic epidemiology. 1988, 5 (6): 10.1002/gepi.1370050603. Sellers T, Elston R, Stewart C, Rothschild H, Vogler G: Familial risk of cancer among randomly selected cancer probands. Genetic epidemiology. 1988, 5 (6): 10.1002/gepi.1370050603.
42.
go back to reference Tokuhata G, Lilienfeld A: Familial aggregation of lung cancer in humans. Journal of the National Cancer Institute. 1963, 30: 289-PubMed Tokuhata G, Lilienfeld A: Familial aggregation of lung cancer in humans. Journal of the National Cancer Institute. 1963, 30: 289-PubMed
43.
go back to reference Guo H: Arsenic level in drinking water and mortality of lung cancer (Taiwan). Cancer Causes and Control. 2004, 15 (2): 171-177. 10.1023/B:CACO.0000019503.02851.b0.CrossRefPubMed Guo H: Arsenic level in drinking water and mortality of lung cancer (Taiwan). Cancer Causes and Control. 2004, 15 (2): 171-177. 10.1023/B:CACO.0000019503.02851.b0.CrossRefPubMed
44.
go back to reference Hertz-Picciotto I, Smith A: Observations on the dose-response curve for arsenic exposure and lung cancer. Scandinavian journal of work, environment & health. 1993, 19 (4): 217-226.CrossRef Hertz-Picciotto I, Smith A: Observations on the dose-response curve for arsenic exposure and lung cancer. Scandinavian journal of work, environment & health. 1993, 19 (4): 217-226.CrossRef
45.
go back to reference Ekberg-Aronsson M, Nilsson P, Nilsson J, Pehrsson K, Löfdahl C: Socio-economic status and lung cancer risk including histologic subtyping--a longitudinal study. Lung cancer. 2006, 51 (1): 21-29. 10.1016/j.lungcan.2005.08.014.CrossRefPubMed Ekberg-Aronsson M, Nilsson P, Nilsson J, Pehrsson K, Löfdahl C: Socio-economic status and lung cancer risk including histologic subtyping--a longitudinal study. Lung cancer. 2006, 51 (1): 21-29. 10.1016/j.lungcan.2005.08.014.CrossRefPubMed
46.
go back to reference Ross S: Diet and DNA methylation interactions in cancer prevention. Annals of the New York Academy of Sciences. 2003, 983: 197-207. 10.1111/j.1749-6632.2003.tb05974.x.CrossRefPubMed Ross S: Diet and DNA methylation interactions in cancer prevention. Annals of the New York Academy of Sciences. 2003, 983: 197-207. 10.1111/j.1749-6632.2003.tb05974.x.CrossRefPubMed
47.
go back to reference Choi S, Mason J: Folate status: effects on pathways of colorectal carcinogenesis. The Journal of nutrition. 2002, 132 (8 Suppl): 2413S-PubMed Choi S, Mason J: Folate status: effects on pathways of colorectal carcinogenesis. The Journal of nutrition. 2002, 132 (8 Suppl): 2413S-PubMed
48.
go back to reference Harnack L, Jacobs D, Nicodemus K, Lazovich D, Anderson K, Folsom A: Relationship of folate, vitamin B-6, vitamin B-12, and methionine intake to incidence of colorectal cancers. Nutrition and cancer. 2002, 43 (2): 152-10.1207/S15327914NC432_5.CrossRefPubMed Harnack L, Jacobs D, Nicodemus K, Lazovich D, Anderson K, Folsom A: Relationship of folate, vitamin B-6, vitamin B-12, and methionine intake to incidence of colorectal cancers. Nutrition and cancer. 2002, 43 (2): 152-10.1207/S15327914NC432_5.CrossRefPubMed
49.
go back to reference Brunaud L, Alberto JM, Ayav A, Gerard P, Namour F, Antunes L, Braun M, Bronowicki JP, Bresler L, Gueant JL: Effects of vitamin B12 and folate deficiencies on DNA methylation and carcinogenesis in rat liver. Clinical Chemistry & Laboratory Medicine. 2003, 41 (8): 1012-1019. 10.1515/CCLM.2003.155.CrossRef Brunaud L, Alberto JM, Ayav A, Gerard P, Namour F, Antunes L, Braun M, Bronowicki JP, Bresler L, Gueant JL: Effects of vitamin B12 and folate deficiencies on DNA methylation and carcinogenesis in rat liver. Clinical Chemistry & Laboratory Medicine. 2003, 41 (8): 1012-1019. 10.1515/CCLM.2003.155.CrossRef
50.
go back to reference Lyn-Cook B, Blann E, Payne P, Bo J, Sheehan D, Medlock K: Methylation profile and amplification of proto-oncogenes in rat pancreas induced with phytoestrogens. SEBM. 1995, 208: 116-119. Lyn-Cook B, Blann E, Payne P, Bo J, Sheehan D, Medlock K: Methylation profile and amplification of proto-oncogenes in rat pancreas induced with phytoestrogens. SEBM. 1995, 208: 116-119.
51.
go back to reference Fang MZ, Wang YM, Ai N, Hou Z, Sun Y, Lu H, Welsh W, Yang CS: Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Research. 2003, 63 (22): 7563-7570.PubMed Fang MZ, Wang YM, Ai N, Hou Z, Sun Y, Lu H, Welsh W, Yang CS: Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Research. 2003, 63 (22): 7563-7570.PubMed
52.
go back to reference Fang MZ, Chen D, Sun Y, Christman JK, Yang CS: Reversal of hypermethylation and reactivation of p16-INK4a, RAR, and MGMT genes by genistein and other isoflavones from soy. Clin Cancer Res. 2005, 11: 7033-7041. 10.1158/1078-0432.CCR-05-0406.CrossRefPubMed Fang MZ, Chen D, Sun Y, Christman JK, Yang CS: Reversal of hypermethylation and reactivation of p16-INK4a, RAR, and MGMT genes by genistein and other isoflavones from soy. Clin Cancer Res. 2005, 11: 7033-7041. 10.1158/1078-0432.CCR-05-0406.CrossRefPubMed
53.
go back to reference Yang CS, Fang M, Lambert JD, Yan P, Huang THM: Reversal of hypermethylation and reactivation of genes by dietary polyphenolic compounds. Nutrition Reviews. 2008, 66: S18-10.1111/j.1753-4887.2008.00059.x.PubMedCentralCrossRefPubMed Yang CS, Fang M, Lambert JD, Yan P, Huang THM: Reversal of hypermethylation and reactivation of genes by dietary polyphenolic compounds. Nutrition Reviews. 2008, 66: S18-10.1111/j.1753-4887.2008.00059.x.PubMedCentralCrossRefPubMed
54.
go back to reference Belinsky SA: Gene-promoter hypermethylation as a biomarker in lung cancer. Nature Reviews Cancer. 2004, 4 (9): 707-717. 10.1038/nrc1432.CrossRefPubMed Belinsky SA: Gene-promoter hypermethylation as a biomarker in lung cancer. Nature Reviews Cancer. 2004, 4 (9): 707-717. 10.1038/nrc1432.CrossRefPubMed
55.
go back to reference Rea S, Eisenhaber F, O'Carroll D, Strahl B, Sun Z, Schmid M, Opravil S, Mechtler K, Ponting C, Allis C: Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature. 2000, 406 (6796): 593-599. 10.1038/35020506.CrossRefPubMed Rea S, Eisenhaber F, O'Carroll D, Strahl B, Sun Z, Schmid M, Opravil S, Mechtler K, Ponting C, Allis C: Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature. 2000, 406 (6796): 593-599. 10.1038/35020506.CrossRefPubMed
56.
go back to reference Candido E, Reeves R, Davie J: Sodium butyrate inhibits histone deacetylation in cultured cells. Cell. 1978, 14 (1): 105-113. 10.1016/0092-8674(78)90305-7.CrossRefPubMed Candido E, Reeves R, Davie J: Sodium butyrate inhibits histone deacetylation in cultured cells. Cell. 1978, 14 (1): 105-113. 10.1016/0092-8674(78)90305-7.CrossRefPubMed
57.
go back to reference Demary K, Wong L, Spanjaard RA: Effects of retinoic acid and sodium butyrate on gene expression, histone acetylation and inhibition of proliferation of melanoma cells. Cancer Letters. 2001, 163 (1): 103-107. 10.1016/S0304-3835(00)00676-5.CrossRefPubMed Demary K, Wong L, Spanjaard RA: Effects of retinoic acid and sodium butyrate on gene expression, histone acetylation and inhibition of proliferation of melanoma cells. Cancer Letters. 2001, 163 (1): 103-107. 10.1016/S0304-3835(00)00676-5.CrossRefPubMed
58.
go back to reference Li M: Identifying susceptibility loci for nicotine dependence: 2008 update based on recent genome-wide linkage analyses. Human Genetics. 2008, 123 (2): 119-131. 10.1007/s00439-008-0473-0.CrossRefPubMed Li M: Identifying susceptibility loci for nicotine dependence: 2008 update based on recent genome-wide linkage analyses. Human Genetics. 2008, 123 (2): 119-131. 10.1007/s00439-008-0473-0.CrossRefPubMed
59.
go back to reference Wang-Sattler R, Yu Y, Mittelstrass K, Lattka E, Altmaier E, Gieger C, Ladwig K, Dahmen N, Weinberger K, Hao P: Metabolic Profiling Reveals Distinct Variations Linked to Nicotine Consumption in Humans--First Results from the KORA Study. PLoS One. 2008, 3 (12): 10.1371/journal.pone.0003863. Wang-Sattler R, Yu Y, Mittelstrass K, Lattka E, Altmaier E, Gieger C, Ladwig K, Dahmen N, Weinberger K, Hao P: Metabolic Profiling Reveals Distinct Variations Linked to Nicotine Consumption in Humans--First Results from the KORA Study. PLoS One. 2008, 3 (12): 10.1371/journal.pone.0003863.
60.
go back to reference Schembri F, Sridhar S, Perdomo C, Gustafson A, Zhang X, Ergun A, Lu J, Liu G, Bowers J: MicroRNAs as modulators of smoking-induced gene expression changes in human airway epithelium. Proceedings of the National Academy of Sciences. 2009, 106 (7): 2319-10.1073/pnas.0806383106.CrossRef Schembri F, Sridhar S, Perdomo C, Gustafson A, Zhang X, Ergun A, Lu J, Liu G, Bowers J: MicroRNAs as modulators of smoking-induced gene expression changes in human airway epithelium. Proceedings of the National Academy of Sciences. 2009, 106 (7): 2319-10.1073/pnas.0806383106.CrossRef
61.
go back to reference Daskalos A, Nikolaidis G, Xinarianos G, Savvari P, Cassidy A, Zakopoulou R, Kotsinas A, Gorgoulis V, Field JK, Liloglou T: Hypomethylation of retrotransposable elements correlates with genomic instability in non-small cell lung cancer. International Journal Of Cancer Journal International Du Cancer. 2009, 124 (1): 81-87. 10.1002/ijc.23849.CrossRefPubMed Daskalos A, Nikolaidis G, Xinarianos G, Savvari P, Cassidy A, Zakopoulou R, Kotsinas A, Gorgoulis V, Field JK, Liloglou T: Hypomethylation of retrotransposable elements correlates with genomic instability in non-small cell lung cancer. International Journal Of Cancer Journal International Du Cancer. 2009, 124 (1): 81-87. 10.1002/ijc.23849.CrossRefPubMed
62.
go back to reference Sidley C, Picchi M, Leng S, Willink R, Crowell R, Flores K, Kang H, Byers T, Gilliland F, Belinsky S: Multi-vitamins, folate, and Green vegetables protect against gene promoter methylation in the aerodigestive tract of smokers. Cancer Research. 2010, 70 (2): 568-574. 10.1158/0008-5472.CAN-09-3410.CrossRef Sidley C, Picchi M, Leng S, Willink R, Crowell R, Flores K, Kang H, Byers T, Gilliland F, Belinsky S: Multi-vitamins, folate, and Green vegetables protect against gene promoter methylation in the aerodigestive tract of smokers. Cancer Research. 2010, 70 (2): 568-574. 10.1158/0008-5472.CAN-09-3410.CrossRef
63.
go back to reference Divine KK, Pulling LC, Marron-Terada PG, Liechty KC, Kang T, Schwartz AG, Bocklage TJ, Coons TA, Gilliland FD, Belinsky SA: Multiplicity of abnormal promoter methylation in lung adenocarcinomas from smokers and never smokers. International Journal Of Cancer Journal International Du Cancer. 2005, 114 (3): 400-405. 10.1002/ijc.20761.CrossRefPubMed Divine KK, Pulling LC, Marron-Terada PG, Liechty KC, Kang T, Schwartz AG, Bocklage TJ, Coons TA, Gilliland FD, Belinsky SA: Multiplicity of abnormal promoter methylation in lung adenocarcinomas from smokers and never smokers. International Journal Of Cancer Journal International Du Cancer. 2005, 114 (3): 400-405. 10.1002/ijc.20761.CrossRefPubMed
64.
go back to reference Zöchbauer-Müller S, Fong K, Virmani A, Geradts J, Gazdar A, Minna J: Aberrant promoter methylation of multiple genes in non-small cell lung cancers. AACR. 2001, 61: 249-255. Zöchbauer-Müller S, Fong K, Virmani A, Geradts J, Gazdar A, Minna J: Aberrant promoter methylation of multiple genes in non-small cell lung cancers. AACR. 2001, 61: 249-255.
65.
go back to reference Feinberg A: Phenotypic plasticity and the epigenetics of human disease. Nature. 2007, 447 (7143): 433-440. 10.1038/nature05919.CrossRefPubMed Feinberg A: Phenotypic plasticity and the epigenetics of human disease. Nature. 2007, 447 (7143): 433-440. 10.1038/nature05919.CrossRefPubMed
66.
go back to reference Suzuki H, Ueda R, Takahashi T: Altered imprinting in lung cancer. Nature Genetics. 1994, 6 (4): 332-333. 10.1038/ng0494-332.CrossRefPubMed Suzuki H, Ueda R, Takahashi T: Altered imprinting in lung cancer. Nature Genetics. 1994, 6 (4): 332-333. 10.1038/ng0494-332.CrossRefPubMed
67.
go back to reference Kohda M, Hoshiya H, Katoh M, Tanaka I, Masuda R, Takemura T, Fujiwara M, Oshimura M: Frequent loss of imprinting of IGF2 and MEST in lung adenocarcinoma. Molecular Carcinogenesis. 2001, 31 (4): 10.1002/mc.1053. Kohda M, Hoshiya H, Katoh M, Tanaka I, Masuda R, Takemura T, Fujiwara M, Oshimura M: Frequent loss of imprinting of IGF2 and MEST in lung adenocarcinoma. Molecular Carcinogenesis. 2001, 31 (4): 10.1002/mc.1053.
68.
go back to reference Herman J, Baylin S: Gene silencing in cancer in association with promoter hypermethylation. New England Journal of Medicine. 2003, 349 (21): 2042-2054. 10.1056/NEJMra023075.CrossRefPubMed Herman J, Baylin S: Gene silencing in cancer in association with promoter hypermethylation. New England Journal of Medicine. 2003, 349 (21): 2042-2054. 10.1056/NEJMra023075.CrossRefPubMed
69.
go back to reference Chen WY, Wang DH, Yen RC, Luo J, Gu W, Baylin SB: Tumor Suppressor HIC1 Directly Regulates SIRT1 to Modulate p53-Dependent DNA-Damage Responses. Cell. 2005, 123 (3): 437-448. 10.1016/j.cell.2005.08.011.CrossRefPubMed Chen WY, Wang DH, Yen RC, Luo J, Gu W, Baylin SB: Tumor Suppressor HIC1 Directly Regulates SIRT1 to Modulate p53-Dependent DNA-Damage Responses. Cell. 2005, 123 (3): 437-448. 10.1016/j.cell.2005.08.011.CrossRefPubMed
70.
go back to reference Chen WY, Baylin SB: Inactivation of tumor suppressor genes: choice between genetic and epigenetic routes. Cell Cycle (Georgetown, Tex). 2005, 4 (1): 10-12.CrossRef Chen WY, Baylin SB: Inactivation of tumor suppressor genes: choice between genetic and epigenetic routes. Cell Cycle (Georgetown, Tex). 2005, 4 (1): 10-12.CrossRef
71.
go back to reference Bartek J, Lukas J: The Stress of Finding NEMO. Science. 2006, 311 (5764): 1110-1111. 10.1126/science.1124540.CrossRefPubMed Bartek J, Lukas J: The Stress of Finding NEMO. Science. 2006, 311 (5764): 1110-1111. 10.1126/science.1124540.CrossRefPubMed
72.
go back to reference Garzon R, Calin GA, Croce CM: MicroRNAs in Cancer. Annual Review Of Medicine. 2009, 60: 167-179. 10.1146/annurev.med.59.053006.104707.CrossRefPubMed Garzon R, Calin GA, Croce CM: MicroRNAs in Cancer. Annual Review Of Medicine. 2009, 60: 167-179. 10.1146/annurev.med.59.053006.104707.CrossRefPubMed
73.
go back to reference Drakaki A, Iliopoulos D: MicroRNA Gene Networks in Oncogenesis. 2009, 10 (1): 35-41. Drakaki A, Iliopoulos D: MicroRNA Gene Networks in Oncogenesis. 2009, 10 (1): 35-41.
74.
go back to reference Vasilatou D, Papageorgiou S, Pappa V, Papageorgiou E, Dervenoulas J: The role of microRNAs in normal and malignant hematopoiesis. European Journal of Haematology. 2009, 9999 (9999): Vasilatou D, Papageorgiou S, Pappa V, Papageorgiou E, Dervenoulas J: The role of microRNAs in normal and malignant hematopoiesis. European Journal of Haematology. 2009, 9999 (9999):
75.
go back to reference Mott J: MicroRNAs involved in tumor suppressor and oncogene pathways; implications for hepatobiliary neoplasia. Hepatology. 2009, 50 (2): 630-7. 10.1002/hep.23010.PubMedCentralCrossRefPubMed Mott J: MicroRNAs involved in tumor suppressor and oncogene pathways; implications for hepatobiliary neoplasia. Hepatology. 2009, 50 (2): 630-7. 10.1002/hep.23010.PubMedCentralCrossRefPubMed
76.
go back to reference Cotter T: Apoptosis and cancer: the genesis of a research field. Nature Reviews Cancer. 2009, 9 (7): 501-507. 10.1038/nrc2663.CrossRefPubMed Cotter T: Apoptosis and cancer: the genesis of a research field. Nature Reviews Cancer. 2009, 9 (7): 501-507. 10.1038/nrc2663.CrossRefPubMed
77.
go back to reference Danial NN: BAD: undertaker by night, candyman by day. Oncogene. 2008, 27 (Suppl 1): S53-70. 10.1038/onc.2009.44.CrossRefPubMed Danial NN: BAD: undertaker by night, candyman by day. Oncogene. 2008, 27 (Suppl 1): S53-70. 10.1038/onc.2009.44.CrossRefPubMed
78.
go back to reference Tse C, Shoemaker A, Adickes J, Anderson M, Chen J, Jin S, Johnson E, Marsh K, Mitten M, Nimmer P: ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Research. 2008, 68 (9): 3421-10.1158/0008-5472.CAN-07-5836.CrossRefPubMed Tse C, Shoemaker A, Adickes J, Anderson M, Chen J, Jin S, Johnson E, Marsh K, Mitten M, Nimmer P: ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Research. 2008, 68 (9): 3421-10.1158/0008-5472.CAN-07-5836.CrossRefPubMed
79.
go back to reference Shoemaker A, Mitten M, Adickes J, Ackler S, Refici M, Ferguson D, Oleksijew A, O'Connor J, Wang B, Frost D: Activity of the Bcl-2 family inhibitor ABT-263 in a panel of small cell lung cancer xenograft models. Clinical Cancer Research. 2008, 14 (11): 3268-10.1158/1078-0432.CCR-07-4622.CrossRefPubMed Shoemaker A, Mitten M, Adickes J, Ackler S, Refici M, Ferguson D, Oleksijew A, O'Connor J, Wang B, Frost D: Activity of the Bcl-2 family inhibitor ABT-263 in a panel of small cell lung cancer xenograft models. Clinical Cancer Research. 2008, 14 (11): 3268-10.1158/1078-0432.CCR-07-4622.CrossRefPubMed
80.
go back to reference Garofalo M, Condorelli G, Croce C, Condorelli G: MicroRNAs as regulators of death receptors signaling. Cell Death & Differentiation. 2009, 17 (2): 200-8. 10.1038/cdd.2009.105.CrossRef Garofalo M, Condorelli G, Croce C, Condorelli G: MicroRNAs as regulators of death receptors signaling. Cell Death & Differentiation. 2009, 17 (2): 200-8. 10.1038/cdd.2009.105.CrossRef
81.
go back to reference Galluzzi LME, Kepp O, Vitalio Rigoni A, Vacchelli E: Mitchondrial gateways to cancer. MOlecular Aspects of Medicine. 2009, 31 (1): 1-20. 10.1016/j.mam.2009.08.002.CrossRefPubMed Galluzzi LME, Kepp O, Vitalio Rigoni A, Vacchelli E: Mitchondrial gateways to cancer. MOlecular Aspects of Medicine. 2009, 31 (1): 1-20. 10.1016/j.mam.2009.08.002.CrossRefPubMed
82.
go back to reference Chen SS, RavaI A, Johnson AJ, Hertlein E, Te-Hui L, Jin VX, Sherman MH, Shu-Jun L, Dawson DW, Williams KE: Epigenetic changes during disease progression in a murine model of human chronic lymphocytic leukemia. Proceedings of the National Academy of Sciences of the United States of America. 2009, 106 (32): 13433-13438. 10.1073/pnas.0906455106.PubMedCentralCrossRefPubMed Chen SS, RavaI A, Johnson AJ, Hertlein E, Te-Hui L, Jin VX, Sherman MH, Shu-Jun L, Dawson DW, Williams KE: Epigenetic changes during disease progression in a murine model of human chronic lymphocytic leukemia. Proceedings of the National Academy of Sciences of the United States of America. 2009, 106 (32): 13433-13438. 10.1073/pnas.0906455106.PubMedCentralCrossRefPubMed
83.
go back to reference McEwen B: Interacting mediators of allostasis and allostatic load: towards an understanding of resilience in aging. Metabolism. 2003, 52: 10-16. 10.1053/S0026-0495(03)00295-6.CrossRefPubMed McEwen B: Interacting mediators of allostasis and allostatic load: towards an understanding of resilience in aging. Metabolism. 2003, 52: 10-16. 10.1053/S0026-0495(03)00295-6.CrossRefPubMed
84.
go back to reference McEwen B, Stellar E: Stress and the individual: mechanisms leading to disease. Archives of Internal Medicine. 1993, 153 (18): 2093-10.1001/archinte.153.18.2093.CrossRefPubMed McEwen B, Stellar E: Stress and the individual: mechanisms leading to disease. Archives of Internal Medicine. 1993, 153 (18): 2093-10.1001/archinte.153.18.2093.CrossRefPubMed
85.
go back to reference McEwen B: Protective and damaging effects of stress mediators. New England Journal of Medicine. 1998, 338 (3): 171-179. 10.1056/NEJM199801153380307.CrossRefPubMed McEwen B: Protective and damaging effects of stress mediators. New England Journal of Medicine. 1998, 338 (3): 171-179. 10.1056/NEJM199801153380307.CrossRefPubMed
86.
go back to reference Bjartveit K, Tverdal A: Health consequences of sustained smoking cessation. British Medical Journal. 2009, 18 (3): 197- Bjartveit K, Tverdal A: Health consequences of sustained smoking cessation. British Medical Journal. 2009, 18 (3): 197-
87.
go back to reference Szanton S, Gill J, Allen J: Allostatic Load: A Mechanism of Socioeconomic Health Disparities?. Biological Research for Nursing. 2005, 7 (1): 7-10.1177/1099800405278216.PubMedCentralCrossRefPubMed Szanton S, Gill J, Allen J: Allostatic Load: A Mechanism of Socioeconomic Health Disparities?. Biological Research for Nursing. 2005, 7 (1): 7-10.1177/1099800405278216.PubMedCentralCrossRefPubMed
88.
go back to reference Geyer S: Social inequalities in the incidence and case fatality of cancers of the lung, the stomach, the bowels, and the breast. Cancer Causes and Control. 2008, 19 (9): 965-974.CrossRefPubMed Geyer S: Social inequalities in the incidence and case fatality of cancers of the lung, the stomach, the bowels, and the breast. Cancer Causes and Control. 2008, 19 (9): 965-974.CrossRefPubMed
89.
go back to reference Chu KC, Miller BA, Springfield SA: Measures of racial/ethnic health disparities in cancer mortality rates and the influence of socioeconomic status. Journal of the National Medical Association. 2007, 99 (10): 1092-1104.PubMedCentralPubMed Chu KC, Miller BA, Springfield SA: Measures of racial/ethnic health disparities in cancer mortality rates and the influence of socioeconomic status. Journal of the National Medical Association. 2007, 99 (10): 1092-1104.PubMedCentralPubMed
90.
go back to reference Lewis DR, Clegg LX, Johnson NJ: Lung disease mortality in the United States: the National Longitudinal Mortality Study. The International Journal Of Tuberculosis And Lung Disease: The Official Journal Of The International Union Against Tuberculosis And Lung Disease. 2009, 13 (8): 1008-1014. Lewis DR, Clegg LX, Johnson NJ: Lung disease mortality in the United States: the National Longitudinal Mortality Study. The International Journal Of Tuberculosis And Lung Disease: The Official Journal Of The International Union Against Tuberculosis And Lung Disease. 2009, 13 (8): 1008-1014.
91.
go back to reference Hausauer AK, Keegan T, Chang ET, Glaser SL, Howe H, Clarke CA: Recent trends in breast cancer incidence in US white women bycounty-level urban/rural and poverty status. BMC Medicine. 2009, 7: 31-42. 10.1186/1741-7015-7-31.PubMedCentralCrossRefPubMed Hausauer AK, Keegan T, Chang ET, Glaser SL, Howe H, Clarke CA: Recent trends in breast cancer incidence in US white women bycounty-level urban/rural and poverty status. BMC Medicine. 2009, 7: 31-42. 10.1186/1741-7015-7-31.PubMedCentralCrossRefPubMed
92.
go back to reference Warnakulasuriya S: Significant oral cancer risk associated with low socioeconomic status. Evidence-Based Dentistry. 2009, 10 (1): 4-5. 10.1038/sj.ebd.6400623.CrossRefPubMed Warnakulasuriya S: Significant oral cancer risk associated with low socioeconomic status. Evidence-Based Dentistry. 2009, 10 (1): 4-5. 10.1038/sj.ebd.6400623.CrossRefPubMed
93.
go back to reference Frederiksen B, Osler M, Harling H, Ladelund S, Jørgensen T: The impact of socioeconomic factors on 30-day mortality following elective colorectal cancer surgery: A nationwide study. European Journal of Cancer. 2009, 45 (7): 1248-1256. 10.1016/j.ejca.2008.11.035.CrossRefPubMed Frederiksen B, Osler M, Harling H, Ladelund S, Jørgensen T: The impact of socioeconomic factors on 30-day mortality following elective colorectal cancer surgery: A nationwide study. European Journal of Cancer. 2009, 45 (7): 1248-1256. 10.1016/j.ejca.2008.11.035.CrossRefPubMed
94.
go back to reference Siegel RL, Jemal A, Thun MJ, Hao Y, Ward EM: Trends in the incidence of colorectal cancer in relation to county-level poverty among blacks and whites. Journal of the National Medical Association. 2008, 100 (12): 1441-1444.PubMed Siegel RL, Jemal A, Thun MJ, Hao Y, Ward EM: Trends in the incidence of colorectal cancer in relation to county-level poverty among blacks and whites. Journal of the National Medical Association. 2008, 100 (12): 1441-1444.PubMed
95.
go back to reference Ou S-HI, Ziogas A, Zell JA: Prognostic factors for survival in extensive stage small cell lung cancer (ED-SCLC): the importance of smoking history, socioeconomic and marital statuses, and ethnicity. Journal Of Thoracic Oncology: Official Publication Of The International Association For The Study Of Lung Cancer. 2009, 4 (1): 37-43.CrossRef Ou S-HI, Ziogas A, Zell JA: Prognostic factors for survival in extensive stage small cell lung cancer (ED-SCLC): the importance of smoking history, socioeconomic and marital statuses, and ethnicity. Journal Of Thoracic Oncology: Official Publication Of The International Association For The Study Of Lung Cancer. 2009, 4 (1): 37-43.CrossRef
96.
go back to reference Cherkas LF, Aviv A, Valdes AM, Hunkin JL, Gardner JP, Surdulescu GL, Kimura M, Spector TD: The effects of social status on biological aging as measured by white-blood-cell telomere length. Aging Cell. 2006, 5 (5): 361-365. 10.1111/j.1474-9726.2006.00222.x.CrossRefPubMed Cherkas LF, Aviv A, Valdes AM, Hunkin JL, Gardner JP, Surdulescu GL, Kimura M, Spector TD: The effects of social status on biological aging as measured by white-blood-cell telomere length. Aging Cell. 2006, 5 (5): 361-365. 10.1111/j.1474-9726.2006.00222.x.CrossRefPubMed
97.
go back to reference Epel ES, Lin J, Wilhelm FH, Wolkowitz OM, Cawthon R, Adler NE, Dolbier C, Mendes WB, Blackburn EH: Cell aging in relation to stress arousal and cardiovascular disease risk factors. Psychoneuroendocrinology. 2006, 31 (3): 277-287. 10.1016/j.psyneuen.2005.08.011.CrossRefPubMed Epel ES, Lin J, Wilhelm FH, Wolkowitz OM, Cawthon R, Adler NE, Dolbier C, Mendes WB, Blackburn EH: Cell aging in relation to stress arousal and cardiovascular disease risk factors. Psychoneuroendocrinology. 2006, 31 (3): 277-287. 10.1016/j.psyneuen.2005.08.011.CrossRefPubMed
98.
go back to reference Chen E, Hanson MD, Paterson LQ, Griffin MJ, Walker HA, Miller GE: Socioeconomic status and inflammatory processes in childhood asthma: the role of psychological stress. The Journal Of Allergy And Clinical Immunology. 2006, 117 (5): 1014-1020. 10.1016/j.jaci.2006.01.036.CrossRefPubMed Chen E, Hanson MD, Paterson LQ, Griffin MJ, Walker HA, Miller GE: Socioeconomic status and inflammatory processes in childhood asthma: the role of psychological stress. The Journal Of Allergy And Clinical Immunology. 2006, 117 (5): 1014-1020. 10.1016/j.jaci.2006.01.036.CrossRefPubMed
99.
go back to reference Pretscher D, Distel L, Grabenbauer G, Wittlinger M, Buettner M, Niedobitek G: Distribution of immune cells in head and neck cancer: CD8+ T-cells and CD20+ B-cells in metastatic lymph nodes are associated with favourable outcome in patients with oro-and hypopharyngeal carcinoma. BMC cancer. 2009, 9 (1): 292-10.1186/1471-2407-9-292.PubMedCentralCrossRefPubMed Pretscher D, Distel L, Grabenbauer G, Wittlinger M, Buettner M, Niedobitek G: Distribution of immune cells in head and neck cancer: CD8+ T-cells and CD20+ B-cells in metastatic lymph nodes are associated with favourable outcome in patients with oro-and hypopharyngeal carcinoma. BMC cancer. 2009, 9 (1): 292-10.1186/1471-2407-9-292.PubMedCentralCrossRefPubMed
100.
go back to reference Dhabhar F, Mcewen B: Acute Stress Enhances while Chronic Stress Suppresses Cell-Mediated Immunityin Vivo: A Potential Role for Leukocyte Trafficking. Brain Behavior and immunity. 1997, 11 (4): 286-306. 10.1006/brbi.1997.0508.CrossRef Dhabhar F, Mcewen B: Acute Stress Enhances while Chronic Stress Suppresses Cell-Mediated Immunityin Vivo: A Potential Role for Leukocyte Trafficking. Brain Behavior and immunity. 1997, 11 (4): 286-306. 10.1006/brbi.1997.0508.CrossRef
Metadata
Title
From 'omics' to complex disease: a systems biology approach to gene-environment interactions in cancer
Author
Sarah S Knox
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2010
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-10-11

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