Oxidative Stress and DNA Damage in Obesity-Related Tumorigenesis

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 824)


Reactive oxygen species induce oxidative modification of critical macromolecules. Oxygen derived free radicals may act as potential cytotoxic intermediates inducing inflammatory and degenerative processes, or as signal messengers for the regulation of gene expression. This dual effect mainly depends on the availability of free radicals in terms of concentration, as well as on the environmental characteristics in which they are produced. The formation of free radicals has been proposed to be the linking factor between certain metabolic disturbances and cancer. Circulating mononuclear cells of patients with high cholesterol levels, insulin resistance, metabolic syndrome or obesity present lower levels of antioxidant enzymes and increased concentrations of oxidative stress by-products such as isoprostanes or the DNA oxidized and highly mutagenic base 8-oxo-7,8-dihydro-2′-deoxyguanosine. Overweight or obese subjects also exhibit hormonal changes as a consequence of the increase of mass fat, and these hormonal alterations have been implicated in the alteration of different signal transduction mechanisms and in cell growth and differentiation. A significant correlation has been found between body mass index and cancer. The biological factors and molecular mechanisms implicated in obesity associated cancer susceptibility will be reviewed.


Cancer DNA damage Free radicals Obesity 



GTS thanks grants from Conselleria de Sanitat de la Generalitat de València and Instituto de Salud Carlos III: ACOM/2012/238; PI10/00802; PI13/01848; CIBEROBN 12/03/30016


  1. 1.
    Sies H, Cadenas E. Oxidative stress: damage to intact cells and organs. Philos Trans R Soc Lond B Biol Sci. 1985;311:617–31.PubMedCrossRefGoogle Scholar
  2. 2.
    Halliwell B, Gutteridge JMC. Free radicals in biology and medicine. 4th ed. Oxford, UK: Oxford University Press; 2007.Google Scholar
  3. 3.
    Loft S, Danielson P, Löhr M, Jantzen K, Hemmingsen JG, Roursgaard M, et al. Urinary excretion of 8-oxo-7,8-dihydroguanine as biomarker of oxidative damage to DNA. Arch Biochem Biophys. 2012;518:142–50.PubMedCrossRefGoogle Scholar
  4. 4.
    Barregard L, Møller P, Henriksen T, Mistry V, Koppen G, Rossner Jr P, et al. Human and methodological sources of variability in the measurement of urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine. Antioxid Redox Signal. 2013;18:2377–91.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Oliva MR, Ripoll F, Muñiz P, Iradi A, Trullenque R, Valls V, et al. Genetic alterations and oxidative metabolism in sporadic colorectal tumors from a Spanish community. Mol Carcinogen. 1997;18:232–43.CrossRefGoogle Scholar
  6. 6.
    Oltra AM, Carbonell F, Tormos C, Iradi A, Sáez GT. Antioxidant enzyme activities and the production of MDA and 8-oxo-dG in chronic lymphocytic leukemia. Free Rad Biol Med. 2001;30:1286–92.PubMedCrossRefGoogle Scholar
  7. 7.
    Sánchez M, Torres JV, Tormos C, Iradi A, Muñiz P, Espinosa O, et al. Impairment of antioxidant enzymes, lipid peroxidation and 8-oxo-2′- deoxyguanosine in advanced epithelial ovarian carcinoma of a spanish community. Cancer Lett. 2006;233:28–35.PubMedCrossRefGoogle Scholar
  8. 8.
    Collado R, Oliver I, Tormos C, Egea M, Miguel A, Cerdá C, et al. Early ROS-mediated DNA damage and oxidative stress biomarkers in monoclonal B lymphocytosis. Cancer Lett. 2012;317:144–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Abdilla N, Tormo MC, Fabia MJ, Chaves FJ, Sáez G, Redon J. Impact of the components of metabolic syndrome on oxidative stress and enzymatic antioxidant activity in essential hypertension. J Hum Hypertens. 2007;21:68–75.PubMedCrossRefGoogle Scholar
  10. 10.
    Martinez-Hervas S, Fandos M, Real JT, Espinosa O, Chaves FJ, Sáez GT, et al. Insulin resistance and oxidative stress in familial combined hyperlipidemia. Atherosclerosis. 2008;199:384–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Fandos M, Corella D, Guillén M, Portloés O, Carrasco P, Iradi A, et al. Impact of cardiovascular risk factors on oxidative stress and DNA damage in a high risk Mediterranean population. Free Radic Res. 2009;43:1179–89.PubMedCrossRefGoogle Scholar
  12. 12.
    Mitjavila MT, Fandos M, Salas-Salvadó J, Covas MI, Borrego S, Estruch R, et al. The Mediterranean diet improves the systemic lipid and DNA oxidative damage in metabolic syndrome individuals. A randomized, controlled trial. Clin Nutr. 2013;32:172–8.PubMedCrossRefGoogle Scholar
  13. 13.
    López-Uriarte P, Nogués R, Saez G, Bulló M, Romeu M, Masana L. Effect of nut consumption on oxidative stress and the endothelial function in metabolic syndrome. Clin Nutr. 2010;29:373–80.PubMedCrossRefGoogle Scholar
  14. 14.
    Real JT, Martínez-Hervás S, Tormos MC, Domenech E, Pallardó FV, Sáez-Tormo G, et al. Increased oxidative stress levels and normal antioxidant enzyme activity in circulating mononuclear cells from patients of familial hypercholesterolemia. Metabolism. 2010;59:293–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Kushino Y, Mori F, Kasai H, Inoue H, Iwai S, Miura K, et al. Misreading of DNA templates containing 8-hydroxy-deoxyguanosine at the modified base and at adjacent residues. Nature. 1987;327:77–9.CrossRefGoogle Scholar
  16. 16.
    Shibutani S, Takeshita M, Grollman AP. Insertion of specific bases during DNA synthesis past the oxidation-damage base 8-oxo-Dg. Nature. 1991;349:431–4.PubMedCrossRefGoogle Scholar
  17. 17.
    Klungland A, Rosewell I, Hollenbach S, Larsen E, Daly G, Epe B, et al. Accumulation of premutagenic DNA lesions in mice defective in removal of oxidative base damage. Proc Natl Acad Sci U S A. 1999;96:13300–5.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Lichtman MA. Obesity and the risk for a haematological malignancy: leukemia, lymphoma, or myeloma. Oncologist. 2010;15:1083–101.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Robert DL, Dive C, Renehan AF. Biological mechanisms linking obesity and cancer risk. New perspectives. Annu Rev Med. 2010;61:301–6.CrossRefGoogle Scholar
  20. 20.
    Lobstein T, Frelut ML. Prevalence of overweight among children in Europe. Obes Rev. 2003;4:195–200.PubMedCrossRefGoogle Scholar
  21. 21.
    Caballero B. The global epidemic of obesity: an overview. Epidemiol Rev. 2007;29:1–5.PubMedCrossRefGoogle Scholar
  22. 22.
    Wang Y, Lobstein T. Worldwide trends in childhood overweight and obesity. Int J Pediatr Obes. 2006;1:11–25.PubMedCrossRefGoogle Scholar
  23. 23.
    De Onis M, Onyango AW, Borghi E, Siyam A, Nishida C, Siekmann J. Development of a WHO growth reference for school-aged children and adolescents. Bull World Health Organ. 2007;85:660–7.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Sánchez-Cruz JJ, Jiménez-Moleón JJ, Fernández-Quesada F, Sánchez MJ. Prevalencia de obesidad infantil y juvenil en España en 2012. Rev Esp Cardiol. 2013;66:371–6.CrossRefGoogle Scholar
  25. 25.
    Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults. 1999–2008. JAMA. 2010;303:235–41.PubMedCrossRefGoogle Scholar
  26. 26.
    Demark-Wahnefried W, Platz EA, Ligibel JA, Blair CK, Courneya KS, Meyerhardt JA, et al. The role of obesity in cancer survival and recurrence. Cancer Epidemiol Biomarkers Prev. 2012;21:1244–59.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Haslam D. Obesity: a medical history. Obes Rev. 2007;8 Suppl 1:31–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Renehan AG, Tyson M, Egger M, Heller F, Swahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 2008;371:569–78.PubMedCrossRefGoogle Scholar
  29. 29.
    Cao Y, Ma J. Body mass index, prostate cancer-specific mortality, and biochemical recurrence: a systematic review and meta-analysis. Cancer Prev Res. 2011;4:486–501.CrossRefGoogle Scholar
  30. 30.
    Ewertz M, Jensen MB, Grunnarsdottir KA, Højris I, Jakobsen EH, Nielsen D, et al. Effect of obesity on prognosis after early-stage breast cancer. J Clin Oncol. 2011;29:25–31.PubMedCrossRefGoogle Scholar
  31. 31.
    Sinicrope FA, Foster NR, Sargent DJ. Obesity is an independent prognostic variable in colon cancer survivors. Clin Cancer Res. 2010;16:1884–93.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Protani M, Coory M, Marin JH. Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. Breast Cancer Res Treat. 2010;123:627–35.PubMedCrossRefGoogle Scholar
  33. 33.
    Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348:1625–38.PubMedCrossRefGoogle Scholar
  34. 34.
    Wholin KY, Carson K, Colditz GA. Obesity and cancer. Oncologist. 2010;15:556–65.CrossRefGoogle Scholar
  35. 35.
    Reeves GK, Pirie K, Beral V, Green J, Spencer E, Bull D. Cancer incidence and mortality in relation to body mass index in the million women study: cohort study. Brit Med J. 2007;335:1134–9.PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Dalling JR, Malone KE, Doody DR, Johnson LG, Gralow JR, Porter PL. Relation of body mass index to tumor markers and survival among young women with invasive ductal breast carcinoma. Cancer. 2001;92:720–9.CrossRefGoogle Scholar
  37. 37.
    De Pergola G, Silvestris F. Obesity as a major risk factor for cancer. J Obes. 2013;2013:291546.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer. 2004;4:579–91.PubMedCrossRefGoogle Scholar
  39. 39.
    Hsing AW, Sakoda LC, Chua Jr S. Obesity, metabolic syndrome, and prostate cancer. Am J Clin Nutr. 2007;86:843–57.Google Scholar
  40. 40.
    Spindler SR. Rapid and reversible induction of the longevity, anticancer and genomic effects of caloric restriction. Mech Ageing Dev. 2005;126:960–6.PubMedCrossRefGoogle Scholar
  41. 41.
    Pallavi R, Giorgio M, Pelicci PG. Insights into the beneficial effect of caloric/dietary restriction for a healthy and prolonged life. Front Physiol. 2012;3:1–10.CrossRefGoogle Scholar
  42. 42.
    Heydari AR, Unnikrishnan A, Lucente LV, Richardson A. Caloric restriction and genomic stability. Nucleic Acids Res. 2007;35:7485–96.PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    McMillan JR, Sattar N, Lean M, McArdle CS. Obesity and cancer. Brit Med J. 2006;333:1109–11.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Lagunova Z, Projnicu AC, Grant WB, Bruland O, Moan JE. Obesity and increased risk of cancer: dose decrease of serum 25-hydroxyvitamin D level with increasing body mass index explain some of the association? Mol Nutr Food Res. 2010;54:1127–33.PubMedGoogle Scholar
  45. 45.
    McKeown-Eyssen G. Epidemiology of colorectal cancer revisited: are serum triglycerides and/or plasma glucose associated with risk? Cancer Epidemiol Biomarkers Prev. 1994;3:687–95.PubMedGoogle Scholar
  46. 46.
    Giovannucci E. Insulin and colon cancer. Cancer Causes Control. 1995;6:164–79.PubMedCrossRefGoogle Scholar
  47. 47.
    Frystyk J. Free insulin-like growth factors-measurements and relationships to growth hormone secretion and glucose homeostasis. Growth Horm IGF Res. 2004;14:337–75.PubMedCrossRefGoogle Scholar
  48. 48.
    Becker S, Lossus L, Kaaks R. Obesity related hyperinsulinaemia and hyperglycaemia and cancer development. Arch Physiol Biochem. 2009;115:86–96.PubMedCrossRefGoogle Scholar
  49. 49.
    Pisani P. Hyper-insulinaemia and cancer, meta-analyses of epidemiological studies. Arch Physiol Biochem. 2008;114:63–70.PubMedCrossRefGoogle Scholar
  50. 50.
    Cust AE, Allen NE, Rinaldi S, Dossus L, Friedenreich C, Olsen A, et al. Serum levels of C-peptide, IGFBP-1 and IGFBP-2 and endometrial cancer risk: results from the European prospective investigation into cancer and nutrition. Int J Cancer. 2007;120:2656–64.PubMedCrossRefGoogle Scholar
  51. 51.
    Verheus M, Peeters PH, Rinaldi S, Dossus L, Biessy C, Olsen A, et al. Serum C-peptide levels and breast cancer risk: results from the European prospective investigation into cancer and nutrition (EPIC). Int J Cancer. 2006;119:659–67.PubMedCrossRefGoogle Scholar
  52. 52.
    Renehan AG, Frystyk J, Flyvbjerg A. Obesity and cancer risk: the role of the insulin-IGF axis. Trends Endocrinol Metab. 2006;17:328–36.PubMedCrossRefGoogle Scholar
  53. 53.
    Richart W, Fernandez-Real JM. No decrease in free IGF-I with increasing insulin in obesity-related insulin resistance. Obes Res. 2001;9:631–6.CrossRefGoogle Scholar
  54. 54.
    Pollak MN, Schernhammer ES, Hankinson SE. Insulin-like growth factor and neoplasia. Nat Rev Cancer. 2004;4:505–18.PubMedCrossRefGoogle Scholar
  55. 55.
    Wu Y, Yakar S, Zhao L, Hennighausen L, LeRoith D. Circulating insulin-like growth factor-I levels regulate colon cancer growth and metastasis. Cancer Res. 2002;62:1030–5.PubMedGoogle Scholar
  56. 56.
    Heron-Milhavet L, LeRoith D. Insulin-like growth factor I induces MDM-dependent degradation of p53 via the p38 MAPK pathway in response to DNA damage. J Biol Chem. 2002;18:15600–6.CrossRefGoogle Scholar
  57. 57.
    Canonici A, Steelant W, Rigot V, Khomitch-Baud A, Boutaghou-Cherid H, Bruyneel E. Insulin-like growth factor-I receptor, E-cadherin and alpha v integrin form a dynamic complex under the control of alpha-catenin. Int J Cancer. 2008;122:572–82.PubMedCrossRefGoogle Scholar
  58. 58.
    Bray GA. The underlying basis for obesity: relationship to cancer. J Nutr. 2002;132:3451s–5.PubMedGoogle Scholar
  59. 59.
    Rose DP, Komninou D, Stephenson GD. Obesity, adipocytokines, and insulin resistance in breast cancer. Obes Rev. 2004;5:153–65.PubMedCrossRefGoogle Scholar
  60. 60.
    Hardwick JC, Van Den Brink GR, Offerhaus GJ, Van Deventer SJ, Peppelenbosch MP. Leptin is a growth factor for colonic epithelial cells. Gastroenterology. 2001;121:79–90.PubMedCrossRefGoogle Scholar
  61. 61.
    Dieudonne MN, Machinal-Quelin F, Serazin-Leroy V, Leneveu MC, Pecquery R, Giudicelli Y. Leptin mediates a proliferative response in human MCF7 breast cancer cells. Biochem Biophys Res Commun. 2002;293:622–8.PubMedCrossRefGoogle Scholar
  62. 62.
    Barb D, Williams CJ, Neuwirth AK, Mantzoros CS. Adiponectin in relation to malignancies: a review of existing basic research and clinical evidence. Am J Clin Nutr. 2007;86:s858–66.PubMedGoogle Scholar
  63. 63.
    Arcidiacono B, Iiritano S, Nocera A, Possidente K, Nevolo MT, Ventura V, et al. Insulin resistance and cancer risk: an overview of the pathogenetic mechanisms. Exp Diabetes Res. 2012;2012:789174.PubMedCentralPubMedCrossRefGoogle Scholar
  64. 64.
    Petridou E, Mantzoros C, Dessypris N, Koukoulomatis P, Addy C, Voulgaris Z, et al. Plasma adiponectin concentrations in relation to endometrial cancer: a case-control study in Greece. J Clin Endocrinol Metab. 2003;88:993–7.PubMedCrossRefGoogle Scholar
  65. 65.
    Miyoshi Y, Funahashi T, Kihara S, Taguchi T, Tamaki Y, Matsuzawa Y, et al. Association of serum adiponectin levels with breast cancer risk. Clin Cancer Res. 2003;9:5699–704.PubMedGoogle Scholar
  66. 66.
    Goktas S, Yilmaz MI, Caglar K, Sonmez A, Kilic S, Bedir S, et al. Prostate cancer and adiponectin. Urology. 2005;65:1168–72.PubMedCrossRefGoogle Scholar
  67. 67.
    Wei EK, Giovannucci E, Fuchs CS, Willett WC, Mantzoros CS. Low plasma adiponectin levels and risk of colorectal cancer in men: a prospective study. J Natl Cancer Inst. 2005;97:1688–94.PubMedCrossRefGoogle Scholar
  68. 68.
    Dieudonne MN, Bussiere M, Dos Santos E, Leneveu MC, Giudicelli Y, Pecquery R. Adiponectin mediates antiproliferative and apoptotic response in human MCF7 breast cancer cells. Boichem Biophys Res Commun. 2006;345:271–8.CrossRefGoogle Scholar
  69. 69.
    Bråkenhielm E, Veitonmäki N, Cao R, Kihara S, Matsuzawa Y, Zhivotovsky B, et al. Adiponectin induced antiangiogenic and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc Natl Acad Sci U S A. 2004;101:2476–81.PubMedCentralPubMedCrossRefGoogle Scholar
  70. 70.
    Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, et al. Increased oxidative-stress in obesity and its impact on metabolic syndrome. J Clin Invest. 2004;114:1752–61.PubMedCentralPubMedCrossRefGoogle Scholar
  71. 71.
    Rindler PM, Plafker SM, Szweda LI, Kinter M. High dietary fat selectively increases catalase expression within cardiac mitochondria. J Biol Chem. 2013;288:1979–90.PubMedCentralPubMedCrossRefGoogle Scholar
  72. 72.
    Dröse S, Brandt U. Molecular mechanisms of superoxide production by the mitochondrial respiratory chain. Adv Exp Med Biol. 2012;748:145–69.PubMedCrossRefGoogle Scholar
  73. 73.
    Diaz-Marco MT, Moscat J. The atypical PKCs in inflammation: NFkB and beyond. Immunol Rev. 2012;246:154–67.CrossRefGoogle Scholar
  74. 74.
    Patel C, Ghanim H, Ravishankar S, Sia CL, Viswanathan P, Mohanty P, et al. Prolonged reactive oxygen species generation and nuclear factor-kappaB activation after a high-fat, high-carbohydrate meal in the obese. J Clin Endocrinol Metabol. 2007;92:4476–9.CrossRefGoogle Scholar
  75. 75.
    Bubici C, Papa S, Dean K, Franzoso G. Mutual cross-talk between reactive oxygen species and nuclear factor-kappa B: molecular basis and biological significance. Oncogene. 2006;25:6731–48.PubMedCrossRefGoogle Scholar
  76. 76.
    Surmi BK, Hasty AH. The role of chemokines in recruitment of immune cells to the artery wall and adipose tissue. Vasc Pharmacol. 2010;52:27–36.CrossRefGoogle Scholar
  77. 77.
    Itoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y, et al. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun. 1997;236:313–22.PubMedCrossRefGoogle Scholar
  78. 78.
    Shin S, Wakabayashi J, Yates MS, Wakabayashi N, Dolan PM, Aja S, et al. Role of Nrf2 in prevention of high-fat diet-induced obesity by synthetic triterpenoid CDDO-imidazolide. Eur J Pharmacol. 2009;620:138–44.PubMedCentralPubMedCrossRefGoogle Scholar
  79. 79.
    Brown LA, Kerr CJ, Whiting P, Finer N, McEneny J, Ashton T. Oxidant stress in healthy normal-weight, overweight, and obese individuals. Obesity. 2009;17:460–6.PubMedCrossRefGoogle Scholar
  80. 80.
    Savini I, Catani MV, Evangelista D, Gasperi V, Avigliano L. Obesity-associated oxidative stress: strategies finalized to improve redox state. Int J Mol Sci. 2013;14:10947–538.CrossRefGoogle Scholar
  81. 81.
    Ferretti G, Bacchetti T, Masciangelo S, Bicchiega V. HDL-paraoxonase and membrane lipid peroxidation: a comparison between healthy and obese subjects. Obesity. 2010;18:1079–84.PubMedCrossRefGoogle Scholar
  82. 82.
    Krzystek-Korpacka M, Patryn E, Hotowy K, Czapińska E, Majda J, Kustrzeba-Wójcicka I, et al. Paraoxonase (PON)-1 activity in overweight and obese children and adolescents: association with obesity-related inflammation and oxidative stress. Adv Clin Exp Med. 2013;22:229–36.PubMedGoogle Scholar
  83. 83.
    Ferré N, Feliu A, García-Heredia A, Marsillach J, París N, Zaragoza-Jordana M, et al. Impaired paraoxonase-1 status in obese children. Relationships with insulin resistance and metabolic syndrome. Clin Biochem. 2013;46:1830–6.PubMedCrossRefGoogle Scholar
  84. 84.
    Canoy D, Wareham N, Welch A, Bingham S, Luben R, Day N, Khaw KT. Plasma ascorbic acid concentrations and fat distribution in 19,068 British men and women in the European prospective investigation into cancer and nutrition Norfolk cohort study. Am J Clin Nutr. 2005;82:1203–9.PubMedGoogle Scholar
  85. 85.
    D’Archivio M, Annuzzi G, Varì R, Filesi C, Giacco R, Scazzocchio B, et al. Predominant role of obesity/insulin resistance in oxidative development. Eur J Clin Invest. 2012;42:70–8.PubMedCrossRefGoogle Scholar
  86. 86.
    De Tursi-Ríspoli L, Vázquez-Tarragón A, Vázquez-Prado A, Sáez-Tormo G, Alí-Mahmoud A, Gumbau-Puchol V. Estrés oxidativo; estudio comparativo entre un grupo de población normal y un grupo de población obesa mórbida. Nutr Hosp. 2013;28:671–5.PubMedGoogle Scholar
  87. 87.
    De Tursi-Ríspoli L, Vázquez-Tarragón A, Vázquez-Prado A, Sáez-Tormo G, Mahmoud AL, Bruna-Esteban M, et al. Relationship of oxidative stress and weight loss achieved in morbid obese patients by means of bariatric surgery using the duodenal switch technique. Nutr Hosp. 2013;28:1085–92.PubMedGoogle Scholar
  88. 88.
    Dandona P, Aljada A, Chaudhuri A, Mohanty P, Garg R. Metabolic syndrome: a comprehensive perspective based on interactions between obesity, diabetes, and inflammation. Circulation. 2005;111:1448–54.PubMedCrossRefGoogle Scholar
  89. 89.
    Il’yasova D, Wang F, Spasojevic I, Base K, D’Agostino Jr RB, Wagenknecht LE. Urinary F2-isoprostanes, obesity, and weight gain in the IRAS cohort. Obesity (Silver Spring). 2012;20:1915–21.CrossRefGoogle Scholar
  90. 90.
    Kanaya AM, Wassel CL, Stoddard PJ, Harris TB, Cummings SR, Kritchevsky SB, et al. F2-isoprostanes and adiposity in older adults. Obesity (Silver Spring). 2011;19:861–7.CrossRefGoogle Scholar
  91. 91.
    Zhang H, Xie C, Spencer HJ, Zuo C, Higuchi M, Ranganathan G, et al. Obesity and hepatosteatosis in mice with enhanced oxidative DNA damage processing in mitochondria. Am J Pathol. 2011;178:1715–27.PubMedCentralPubMedCrossRefGoogle Scholar
  92. 92.
    Sampath H, Vartanian V, Rollins MR, Sakumi K, Nakabeppu Y, Lloyd RS. 8-Oxoguanine DNA glycosilase (OGG1) deficiency increases susceptibility to obese and metabolic dysfunction. PLoS One. 2012;7:e51697.PubMedCentralPubMedCrossRefGoogle Scholar
  93. 93.
    García-Heredia A, Kensicki E, Mohney RP, Rull A, Triguero I, Marsillach J, et al. Paraoxonase-1 deficiency is associated with severe liver steatosis in mice fed a high-fat high-cholesterol diet. A metabolomic approach. J Proteome Res. 2013;12:1946–55.PubMedCrossRefGoogle Scholar
  94. 94.
    Milić M, Kišan M, Rogulj D, Radman M, Lovrenčić MV, Konjevoda P, et al. Level of primary DNA damage in the early stage of metabolic syndrome. Mutat Res. 2013;758:1–5.PubMedCrossRefGoogle Scholar
  95. 95.
    Anderson D, Yu TW, Wright J, Ioannides C. An explanation of DNA strand breakage in the comet assay and antioxidant capacity in diabetic patients. Mutat Res. 1998;398:151–61.PubMedCrossRefGoogle Scholar
  96. 96.
    Chavarro JE, Toth TL, Wright DL, Meeker JD, Hauser R. Body mass index in relation to semen quality, sperm DNA integrity, and serum reproductive hormone levels among men attending an infertility clinic. Fertil Steril. 2010;93:2222–31.PubMedCentralPubMedCrossRefGoogle Scholar
  97. 97.
    Dupont C, Faure C, Sermondade N, Boubaya M, Eustache F, Clément P, et al. Obesity leads to higher risk of sperm DNA damage in infertile patients. Asian J Androl. 2013;15:622–5.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.Service of Clinical Analysis-CDB, Oxidative Stress Commission-SEQCGeneral University Hospital-CIBEROBN, University of ValenciaValenciaSpain
  2. 2.Endocrinology and Nutrition UnitGeneral University Hospital, University of ValenciaValenciaSpain
  3. 3.Service of Internal MedicineGeneral University Hospital, University of ValenciaValenciaSpain
  4. 4.Service of General and Digestive SurgeryGeneral University Hospital, University of ValenciaValenciaSpain
  5. 5.Department of Physiology, Faculty of Medicine-CIBEROBNUniversity of ValenciaValenciaSpain
  6. 6.Department of Biochemistry and Molecular Biology, Faculty of MedicineUniversity of ValenciaValenciaSpain
  7. 7.Department of Biochemistry and Molecular Biology, Faculty of MedicineGeneral University Hospital-CDB, University of Valencia, Oxidative Stress Commission-SEQCValenciaSpain

Personalised recommendations