Obesity, DNA Damage, and Development of Obesity-Related Diseases

Marta Włodarczyk, Grażyna Nowicka, Marta Włodarczyk, Grażyna Nowicka

Abstract

Obesity has been recognized to increase the risk of such diseases as cardiovascular diseases, diabetes, and cancer. It indicates that obesity can impact genome stability. Oxidative stress and inflammation, commonly occurring in obesity, can induce DNA damage and inhibit DNA repair mechanisms. Accumulation of DNA damage can lead to an enhanced mutation rate and can alter gene expression resulting in disturbances in cell metabolism. Obesity-associated DNA damage can promote cancer growth by favoring cancer cell proliferation and migration, and resistance to apoptosis. Estimation of the DNA damage and/or disturbances in DNA repair could be potentially useful in the risk assessment and prevention of obesity-associated metabolic disorders as well as cancers. DNA damage in people with obesity appears to be reversible and both weight loss and improvement of dietary habits and diet composition can affect genome stability.

Keywords: DNA damage; ROS; cancer; inflammation; obesity; oxidative stress.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Overview of DNA damaging agents, induced DNA lesions, and their repair pathways (BER—base excision repair, NER—nucleotide excision repair, MMR—mismatch repair, DR—direct repair, NHEJ—non-homologous end-joining; and HR—homologous recombination). Shortcuts are explained in the abbreviation section.
Figure 2
Figure 2
Obesity and DNA damage. Obesity is associated with inflammation and oxidative stress which induces DNA damage and inhibits DNA damage repair resulting in the accumulation of DNA damage in adipocyte and other tissues.
Figure 3
Figure 3
Obesity-induced DNA damage and development of metabolic disorders.
Figure 4
Figure 4
Obesity-induced DNA damage and cancer development.

References

    1. Leung Y.M., Pollack L.M., Colditz G.A., Chang S.H. Life years lost and lifetime health care expenditures associated with diabetes in the U.S., National Health Interview Survey, 1997–2000. Diabetes Care. 2015;38:460–468. doi: 10.2337/dc14-1453.
    1. Ligibel J.A., Alfano C.M., Courneya K.S., Demark-Wahnefried W., Burger R.A., Chlebowski R.T., Fabian C.J., Gucalp A., Hershman D.L., Hudson M.M., et al. American Society of Clinical Oncology position statement on obesity and cancer. J. Clin. Oncol. 2014;32:3568–3574. doi: 10.1200/JCO.2014.58.4680.
    1. Scherer P.E., Hill J.A. Obesity, diabetes, and cardiovascular diseases: A compendium. Circ. Res. 2016;118:1703–1705. doi: 10.1161/CIRCRESAHA.116.308999.
    1. Cerda C., Sanchez C., Climent B., Vazquez A., Iradi A., El Amrani F., Bediaga A., Saez G.T. Oxidative stress and DNA damage in obesity-related tumorigenesis. Adv. Exp. Med. Biol. 2014;824:5–17.
    1. Wlodarczyk M., Jablonowska-Lietz B., Olejarz W., Nowicka G. Anthropometric and dietary factors as predictors of DNA damage in obese women. Nutrients. 2018;10:578. doi: 10.3390/nu10050578.
    1. Zaki M., Basha W., El-Bassyouni H.T., El-Toukhy S., Hussein T. Evaluation of DNA damage profile in obese women and its association to risk of metabolic syndrome, polycystic ovary syndrome and recurrent preeclampsia. Genes Dis. 2018;5:367–373. doi: 10.1016/j.gendis.2018.03.001.
    1. Irigaray P., Belpomme D. Basic properties and molecular mechanisms of exogenous chemical carcinogens. Carcinogenesis. 2010;31:135–148. doi: 10.1093/carcin/bgp252.
    1. Heilbronn L.K., de Jonge L., Frisard M.I., DeLany J.P., Larson-Meyer D.E., Rood J., Nguyen T., Martin C.K., Volaufova J., Most M.M., et al. Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: A randomized controlled trial. JAMA. 2006;295:1539–1548. doi: 10.1001/jama.295.13.1539.
    1. Chen L., Deng H., Cui H., Fang J., Zuo Z., Deng J., Li Y., Wang X., Zhao L. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2018;9:7204–7218. doi: 10.18632/oncotarget.23208.
    1. Abou-Raya S., Abou-Raya A., Naim A., Abuelkheir H. Chronic inflammatory autoimmune disorders and atherosclerosis. Ann. N. Y. Acad. Sci. 2007;1107:56–67. doi: 10.1196/annals.1381.007.
    1. Lopez-Candales A., Burgos P.M.H., Hernandez-Suarez D.F., Harris D. Linking chronic inflammation with cardiovascular disease: from normal aging to the metabolic syndrome. J. Nat. Sci. 2017;3:e341.
    1. Dan Dunn J., Alvarez L.A., Zhang X., Soldati T. Reactive oxygen species and mitochondria: A nexus of cellular homeostasis. Redox Biol. 2015;6:472–485. doi: 10.1016/j.redox.2015.09.005.
    1. De Bont R., van Larebeke N. Endogenous DNA damage in humans: A review of quantitative data. Mutagenesis. 2004;19:169–185. doi: 10.1093/mutage/geh025.
    1. Yu Y., Cui Y., Niedernhofer L.J., Wang Y. Occurrence, biological consequences, and human health relevance of oxidative stress-induced DNA damage. Chem. Res. Toxicol. 2016;29:2008–2039. doi: 10.1021/acs.chemrestox.6b00265.
    1. Luczaj W., Skrzydlewska E. DNA damage caused by lipid peroxidation products. Cell Mol. Biol. Lett. 2003;8:391–413.
    1. Jena N.R. DNA damage by reactive species: Mechanisms, mutation and repair. J. Biosci. 2012;37:503–517. doi: 10.1007/s12038-012-9218-2.
    1. Kehrer J.P. The Haber-Weiss reaction and mechanisms of toxicity. Toxicology. 2000;149:43–50. doi: 10.1016/S0300-483X(00)00231-6.
    1. Thomas C., Mackey M.M., Diaz A.A., Cox D.P. Hydroxyl radical is produced via the Fenton reaction in submitochondrial particles under oxidative stress: Implications for diseases associated with iron accumulation. Redox Rep. 2009;14:102–108. doi: 10.1179/135100009X392566.
    1. Dedon P.C., Tannenbaum S.R. Reactive nitrogen species in the chemical biology of inflammation. Arch. Biochem. Biophys. 2004;423:12–22. doi: 10.1016/j.abb.2003.12.017.
    1. Kamiya H. Mutagenic potentials of damaged nucleic acids produced by reactive oxygen/nitrogen species: Approaches using synthetic oligonucleotides and nucleotides: Survey and summary. Nucleic Acids Res. 2003;31:517–531. doi: 10.1093/nar/gkg137.
    1. Sova H., Jukkola-Vuorinen A., Puistola U., Kauppila S., Karihtala P. 8-Hydroxydeoxyguanosine: A new potential independent prognostic factor in breast cancer. Br. J. Cancer. 2010;102:1018–1023. doi: 10.1038/sj.bjc.6605565.
    1. McGowan C.H., Russell P. The DNA damage response: Sensing and signaling. Curr. Opin. Cell Biol. 2004;16:629–633. doi: 10.1016/j.ceb.2004.09.005.
    1. Allione A., Guarrera S., Russo A., Ricceri F., Purohit R., Pagnani A., Rosa F., Polidoro S., Voglino F., Matullo G. Inter-individual variation in nucleotide excision repair pathway is modulated by non-synonymous polymorphisms in ERCC4 and MBD4 genes. Mutat. Res. 2013;751–752:49–54. doi: 10.1016/j.mrfmmm.2013.08.005.
    1. Nagel Z.D., Chaim I.A., Samson L.D. Inter-individual variation in DNA repair capacity: A need for multi-pathway functional assays to promote translational DNA repair research. DNA Repair. 2014;19:199–213. doi: 10.1016/j.dnarep.2014.03.009.
    1. Kabzinski J., Mucha B., Cuchra M., Markiewicz L., Przybylowska K., Dziki A., Dziki L., Majsterek I. Efficiency of Base Excision Repair of Oxidative DNA Damage and Its Impact on the Risk of Colorectal Cancer in the Polish Population. Oxid Med. Cell Longev. 2016;2016:3125989. doi: 10.1155/2016/3125989.
    1. Slyskova J., Lorenzo Y., Karlsen A., Carlsen M.H., Novosadova V., Blomhoff R., Vodicka P., Collins A.R. Both genetic and dietary factors underlie individual differences in DNA damage levels and DNA repair capacity. DNA Repair. 2014;16:66–73. doi: 10.1016/j.dnarep.2014.01.016.
    1. Hakem R. DNA-damage repair; the good, the bad, and the ugly. EMBO J. 2008;27:589–605. doi: 10.1038/emboj.2008.15.
    1. Cleaver J.E. Profile of Tomas Lindahl, Paul Modrich, and Aziz Sancar, 2015 Nobel Laureates in Chemistry. Proc. Natl. Acad. Sci. USA. 2016;113:242–245. doi: 10.1073/pnas.1521829112.
    1. Lindahl T., Karran P., Wood R.D. DNA excision repair pathways. Curr. Opin. Genet. Dev. 1997;7:158–169. doi: 10.1016/S0959-437X(97)80124-4.
    1. Sancar A. Excision repair in mammalian cells. J. Biol. Chem. 1995;270:15915–15918. doi: 10.1074/jbc.270.27.15915.
    1. Bukhari S.A., Rajoka M.I., Ibrahim Z., Jalal F., Rana S.M., Nagra S.A. Oxidative stress elevated DNA damage and homocysteine level in normal pregnant women in a segment of Pakistani population. Mol. Biol. Rep. 2011;38:2703–2710. doi: 10.1007/s11033-010-0413-7.
    1. Tomasello B., Malfa G., Galvano F., Reins M. DNA damage in normal-weight obese syndrome measured by Comet assay. Mediterr. J. Nutr. Metab. 2011;2:99–104. doi: 10.1007/s12349-010-0035-6.
    1. Scarpato R., Verola C., Fabiani B., Bianchi V., Saggese G., Federico G. Nuclear damage in peripheral lymphocytes of obese and overweight Italian children as evaluated by the gamma-H2AX focus assay and micronucleus test. FASEB J. 2011;25:685–693. doi: 10.1096/fj.10-168427.
    1. Azzara A., Pirillo C., Giovannini C., Federico G., Scarpato R. Different repair kinetic of DSBs induced by mitomycin C in peripheral lymphocytes of obese and normal weight adolescents. Mutat. Res. 2016;789:9–14. doi: 10.1016/j.mrfmmm.2016.05.001.
    1. Donmez-Altuntas H., Sahin F., Bayram F., Bitgen N., Mert M., Guclu K., Hamurcu Z., Aribas S., Gundogan K., Diri H. Evaluation of chromosomal damage, cytostasis, cytotoxicity, oxidative DNA damage and their association with body-mass index in obese subjects. Mutat. Res. Genet. Toxicol. Environ. Mutagen. 2014;771:30–36. doi: 10.1016/j.mrgentox.2014.06.006.
    1. Karbownik-Lewinska M., Szosland J., Kokoszko-Bilska A., Stepniak J., Zasada K., Gesing A., Lewinski A. Direct contribution of obesity to oxidative damage to macromolecules. Neuro Endocrinol. Lett. 2012;33:453–461.
    1. Kocael A., Erman H., Zengin K., Kocael P.C., Korkmaz G.G., Gelisgen R., Taskin M., Ersan Y., Uzun H. The effects on oxidative DNA damage of laparoscopic gastric band applications in morbidly obese patients. Can. J. Surg. 2014;57:183–187. doi: 10.1503/cjs.008113.
    1. Setayesh T., Nersesyan A., Misik M., Ferk F., Langie S., Andrade V.M., Haslberger A., Knasmuller S. Impact of obesity and overweight on DNA stability: Few facts and many hypotheses. Mutat. Res. 2018;777:64–91. doi: 10.1016/j.mrrev.2018.07.001.
    1. Iyer A., Fairlie D.P., Prins J.B., Hammock B.D., Brown L. Inflammatory lipid mediators in adipocyte function and obesity. Nat. Rev. Endocrinol. 2010;6:71–82. doi: 10.1038/nrendo.2009.264.
    1. Han C.Y. Roles of Reactive Oxygen Species on Insulin Resistance in Adipose Tissue. Diabetes Metab. J. 2016;40:272–279. doi: 10.4093/dmj.2016.40.4.272.
    1. Han C.Y., Umemoto T., Omer M., den Hartigh L.J., Chiba T., LeBoeuf R., Buller C.L., Sweet I.R., Pennathur S., Abel E.D., et al. NADPH oxidase-derived reactive oxygen species increases expression of monocyte chemotactic factor genes in cultured adipocytes. J. Biol. Chem. 2012;287:10379–10393. doi: 10.1074/jbc.M111.304998.
    1. Weisberg S.P., McCann D., Desai M., Rosenbaum M., Leibel R.L., Ferrante A.W., Jr. Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Investig. 2003;112:1796–1808. doi: 10.1172/JCI200319246.
    1. Gao C.L., Zhu C., Zhao Y.P., Chen X.H., Ji C.B., Zhang C.M., Zhu J.G., Xia Z.K., Tong M.L., Guo X.R. Mitochondrial dysfunction is induced by high levels of glucose and free fatty acids in 3T3-L1 adipocytes. Mol. Cell Endocrinol. 2010;320:25–33. doi: 10.1016/j.mce.2010.01.039.
    1. Heo J.W., No M.H., Park D.H., Kang J.H., Seo D.Y., Han J., Neufer P.D., Kwak H.B. Effects of exercise on obesity-induced mitochondrial dysfunction in skeletal muscle. Korean J. Physiol. Pharmacol. 2017;21:567–577. doi: 10.4196/kjpp.2017.21.6.567.
    1. Fehsel K., Kolb-Bachofen V., Kolb H. Analysis of TNF alpha-induced DNA strand breaks at the single cell level. Am. J. Pathol. 1991;139:251–254.
    1. Arango Duque G., Descoteaux A. Macrophage cytokines: Involvement in immunity and infectious diseases. Front. Immunol. 2014;5:491. doi: 10.3389/fimmu.2014.00491.
    1. Rastogi S., Boylan M., Wright E.G., Coates P.J. Interactions of apoptotic cells with macrophages in radiation-induced bystander signaling. Radiat. Res. 2013;179:135–145. doi: 10.1667/RR2969.1.
    1. Speed N., Blair I.A. Cyclooxygenase- and lipoxygenase-mediated DNA damage. Cancer Metastasis Rev. 2011;30:437–447. doi: 10.1007/s10555-011-9298-8.
    1. Faber T.J., Japink D., Leers M.P., Sosef M.N., von Meyenfeldt M.F., Nap M. Activated macrophages containing tumor marker in colon carcinoma: Immunohistochemical proof of a concept. Tumour Biol. 2012;33:435–441. doi: 10.1007/s13277-011-0269-z.
    1. O’Callaghan N.J., Clifton P.M., Noakes M., Fenech M. Weight loss in obese men is associated with increased telomere length and decreased abasic sites in rectal mucosa. Rejuvenation Res. 2009;12:169–176. doi: 10.1089/rej.2008.0819.
    1. Fejfer K., Buczko P., Niczyporuk M., Ladny J.R., Hady H.R., Knas M., Waszkiel D., Klimiuk A., Zalewska A., Maciejczyk M. Oxidative modification of biomolecules in the nonstimulated and stimulated saliva of patients with morbid obesity treated with bariatric surgery. Biomed. Res. Int. 2017;2017:4923769. doi: 10.1155/2017/4923769.
    1. Himbert C., Thompson H., Ulrich C.M. Effects of intentional weight loss on markers of oxidative stress, DNA repair and telomere length—A systematic review. Obes. Facts. 2017;10:648–665. doi: 10.1159/000479972.
    1. Tyson J., Caple F., Spiers A., Burtle B., Daly A.K., Williams E.A., Hesketh J.E., Mathers J.C. Inter-individual variation in nucleotide excision repair in young adults: Effects of age, adiposity, micronutrient supplementation and genotype. Br. J. Nutr. 2009;101:1316–1323. doi: 10.1017/S0007114508076265.
    1. Adcock I.M., Cosio B., Tsaprouni L., Barnes P.J., Ito K. Redox regulation of histone deacetylases and glucocorticoid-mediated inhibition of the inflammatory response. Antioxid. Redox Signal. 2005;7:144–152. doi: 10.1089/ars.2005.7.144.
    1. Kidane D., Chae W.J., Czochor J., Eckert K.A., Glazer P.M., Bothwell A.L., Sweasy J.B. Interplay between DNA repair and inflammation, and the link to cancer. Crit. Rev. Biochem. Mol. Biol. 2014;49:116–139. doi: 10.3109/10409238.2013.875514.
    1. Liu R.H., Hotchkiss J.H. Potential genotoxicity of chronically elevated nitric oxide: A review. Mutat. Res. 1995;339:73–89. doi: 10.1016/0165-1110(95)90004-7.
    1. McAdam E., Brem R., Karran P. Oxidative stress-induced protein damage inhibits DNA repair and determines mutation risk and therapeutic efficacy. Mol. Cancer Res. 2016;14:612–622. doi: 10.1158/1541-7786.MCR-16-0053.
    1. Nikodemova M., Yee J., Carney P.R., Bradfield C.A., Malecki K.M. Transcriptional differences between smokers and non-smokers and variance by obesity as a risk factor for human sensitivity to environmental exposures. Environ. Int. 2018;113:249–258. doi: 10.1016/j.envint.2018.02.016.
    1. Zwamborn R.A., Slieker R.C., Mulder P.C., Zoetemelk I., Verschuren L., Suchiman H.E., Toet K.H., Droog S., Slagboom P.E., Kooistra T., et al. Prolonged high-fat diet induces gradual and fat depot-specific DNA methylation changes in adult mice. Sci. Rep. 2017;7:43261. doi: 10.1038/srep43261.
    1. Keleher M.R., Zaidi R., Hicks L., Shah S., Xing X., Li D., Wang T., Cheverud J.M. A high-fat diet alters genome-wide DNA methylation and gene expression in SM/J mice. BMC Genom. 2018;19:888. doi: 10.1186/s12864-018-5327-0.
    1. Wang D., Zhao R., Qu Y.Y., Mei X.Y., Zhang X., Zhou Q., Li Y., Yang S.B., Zuo Z.G., Chen Y.M., et al. Colonic lysine homocysteinylation induced by high-fat diet suppresses DNA damage repair. Cell Rep. 2018;25:398–412. doi: 10.1016/j.celrep.2018.09.022.
    1. Harreus U., Baumeister P., Zieger S., Matthias C. The influence of high doses of vitamin C and zinc on oxidative DNA damage. Anticancer Res. 2005;25:3197–3201.
    1. Huang H.Y., Helzlsouer K.J., Appel L.J. The effects of vitamin C and vitamin E on oxidative DNA damage: Results from a randomized controlled trial. Cancer Epidemiol. Biomark. Prev. 2000;9:647–652.
    1. Remely M., Ferk F., Sterneder S., Setayesh T., Roth S., Kepcija T., Noorizadeh R., Rebhan I., Greunz M., Beckmann J., et al. EGCG prevents high fat diet-induced changes in gut microbiota, decreases of DNA strand breaks, and changes in expression and DNA methylation of Dnmt1 and MLH1 in C57BL/6J male mice. Oxid Med. Cell Longev. 2017;2017:3079148. doi: 10.1155/2017/3079148.
    1. Remely M., Ferk F., Sterneder S., Setayesh T., Kepcija T., Roth S., Noorizadeh R., Greunz M., Rebhan I., Wagner K.H., et al. Vitamin E modifies high-fat diet-induced increase of DNA strand breaks, and changes in expression and DNA methylation of Dnmt1 and MLH1 in C57BL/6J male mice. Nutrients. 2017;9:607. doi: 10.3390/nu9060607.
    1. Van Houten B., Hunter S.E., Meyer J.N. Mitochondrial DNA damage induced autophagy, cell death, and disease. Front. Biosci. 2016;21:42–54. doi: 10.2741/4375.
    1. Stein A., Sia E.A. Mitochondrial DNA repair and damage tolerance. Front. Biosci. 2017;22:920–943.
    1. Taanman J.W. The mitochondrial genome: Structure, transcription, translation and replication. Biochim. Biophys. Acta. 1999;1410:103–123. doi: 10.1016/S0005-2728(98)00161-3.
    1. Wang J., Xiong S., Xie C., Markesbery W.R., Lovell M.A. Increased oxidative damage in nuclear and mitochondrial DNA in Alzheimer’s disease. J. Neurochem. 2005;93:953–962. doi: 10.1111/j.1471-4159.2005.03053.x.
    1. Nishikawa M., Oshitani N., Matsumoto T., Nishigami T., Arakawa T., Inoue M. Accumulation of mitochondrial DNA mutation with colorectal carcinogenesis in ulcerative colitis. Br. J. Cancer. 2005;93:331–337. doi: 10.1038/sj.bjc.6602664.
    1. Bensch K.G., Mott J.L., Chang S.W., Hansen P.A., Moxley M.A., Chambers K.T., de Graaf W., Zassenhaus H.P., Corbett J.A. Selective mtDNA mutation accumulation results in beta-cell apoptosis and diabetes development. Am. J. Physiol. Endocrinol. Metab. 2009;296:E672–E680. doi: 10.1152/ajpendo.90839.2008.
    1. Chinnery P.F., Hudson G. Mitochondrial genetics. Br. Med. Bull. 2013;106:135–159. doi: 10.1093/bmb/ldt017.
    1. Sutherland L.N., Capozzi L.C., Turchinsky N.J., Bell R.C., Wright D.C. Time course of high-fat diet-induced reductions in adipose tissue mitochondrial proteins: Potential mechanisms and the relationship to glucose intolerance. Am. J. Physiol. Endocrinol. Metab. 2008;295:E1076–E1083. doi: 10.1152/ajpendo.90408.2008.
    1. Turner N., Bruce C.R., Beale S.M., Hoehn K.L., So T., Rolph M.S., Cooney G.J. Excess lipid availability increases mitochondrial fatty acid oxidative capacity in muscle: Evidence against a role for reduced fatty acid oxidation in lipid-induced insulin resistance in rodents. Diabetes. 2007;56:2085–2092. doi: 10.2337/db07-0093.
    1. Lee H., Oh S., Yang W., Park R., Kim H., Jeon J.S., Noh H., Han D.C., Cho K.W., Kim Y.J., et al. Bariatric surgery reduces elevated urinary mitochondrial DNA copy number in obese patients. J. Clin. Endocrinol. Metab. 2019 doi: 10.1210/jc.2018-01935.
    1. Yuzefovych L.V., Musiyenko S.I., Wilson G.L., Rachek L.I. Mitochondrial DNA damage and dysfunction, and oxidative stress are associated with endoplasmic reticulum stress, protein degradation and apoptosis in high fat diet-induced insulin resistance mice. PLoS ONE. 2013;8:e54059. doi: 10.1371/journal.pone.0054059.
    1. Pazmandi K., Agod Z., Kumar B.V., Szabo A., Fekete T., Sogor V., Veres A., Boldogh I., Rajnavolgyi E., Lanyi A., et al. Oxidative modification enhances the immunostimulatory effects of extracellular mitochondrial DNA on plasmacytoid dendritic cells. Free Radic. Biol. Med. 2014;77:281–290. doi: 10.1016/j.freeradbiomed.2014.09.028.
    1. Shimada K., Crother T.R., Karlin J., Dagvadorj J., Chiba N., Chen S., Ramanujan V.K., Wolf A.J., Vergnes L., Ojcius D.M., et al. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity. 2012;36:401–414. doi: 10.1016/j.immuni.2012.01.009.
    1. Patro B., Liber A., Zalewski B., Poston L., Szajewska H., Koletzko B. Maternal and paternal body mass index and offspring obesity: A systematic review. Ann. Nutr. Metab. 2013;63:32–41. doi: 10.1159/000350313.
    1. Wahl S., Drong A., Lehne B., Loh M., Scott W.R., Kunze S., Tsai P.C., Ried J.S., Zhang W., Yang Y., et al. Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity. Nature. 2017;541:81–86. doi: 10.1038/nature20784.
    1. Campbell J.M., Lane M., Owens J.A., Bakos H.W. Paternal obesity negatively affects male fertility and assisted reproduction outcomes: A systematic review and meta-analysis. Reprod. Biomed. Online. 2015;31:593–604. doi: 10.1016/j.rbmo.2015.07.012.
    1. Kort H.I., Massey J.B., Elsner C.W., Mitchell-Leef D., Shapiro D.B., Witt M.A., Roudebush W.E. Impact of body mass index values on sperm quantity and quality. J. Androl. 2006;27:450–452. doi: 10.2164/jandrol.05124.
    1. Evenson D.P., Wixon R. Clinical aspects of sperm DNA fragmentation detection and male infertility. Theriogenology. 2006;65:979–991. doi: 10.1016/j.theriogenology.2005.09.011.
    1. Abdelbaki S.A., Sabry J.H., Al-Adl A.M., Sabry H.H. The impact of coexisting sperm DNA fragmentation and seminal oxidative stress on the outcome of varicocelectomy in infertile patients: A prospective controlled study. Arab. J. Urol. 2017;15:131–139. doi: 10.1016/j.aju.2017.03.002.
    1. Tunc O., Bakos H.W., Tremellen K. Impact of body mass index on seminal oxidative stress. Andrologia. 2011;43:121–128. doi: 10.1111/j.1439-0272.2009.01032.x.
    1. Lezaja A., Altmeyer M. Inherited DNA lesions determine G1 duration in the next cell cycle. Cell Cycle. 2018;17:24–32. doi: 10.1080/15384101.2017.1383578.
    1. Soubry A. Epigenetic inheritance and evolution: A paternal perspective on dietary influences. Prog. Biophys. Mol. Biol. 2015;118:79–85. doi: 10.1016/j.pbiomolbio.2015.02.008.
    1. Hammoud S.S., Nix D.A., Hammoud A.O., Gibson M., Cairns B.R., Carrell D.T. Genome-wide analysis identifies changes in histone retention and epigenetic modifications at developmental and imprinted gene loci in the sperm of infertile men. Hum. Reprod. 2011;26:2558–2569. doi: 10.1093/humrep/der192.
    1. McPherson N.O., Fullston T., Aitken R.J., Lane M. Paternal obesity, interventions, and mechanistic pathways to impaired health in offspring. Ann. Nutr. Metab. 2014;64:231–238. doi: 10.1159/000365026.
    1. Noblanc A., Damon-Soubeyrand C., Karrich B., Henry-Berger J., Cadet R., Saez F., Guiton R., Janny L., Pons-Rejraji H., Alvarez J.G., et al. DNA oxidative damage in mammalian spermatozoa: Where and why is the male nucleus affected? Free Radic. Biol. Med. 2013;65:719–723. doi: 10.1016/j.freeradbiomed.2013.07.044.
    1. Palmer N.O., Fullston T., Mitchell M., Setchell B.P., Lane M. SIRT6 in mouse spermatogenesis is modulated by diet-induced obesity. Reprod. Fertil. Dev. 2011;23:929–939. doi: 10.1071/RD10326.
    1. Van Gaal L.F., Mertens I.L., de Block C.E. Mechanisms linking obesity with cardiovascular disease. Nature. 2006;444:875–880. doi: 10.1038/nature05487.
    1. Shimizu I., Yoshida Y., Suda M., Minamino T. DNA damage response and metabolic disease. Cell Metab. 2014;20:967–977. doi: 10.1016/j.cmet.2014.10.008.
    1. Vousden K.H., Lane D.P. p53 in health and disease. Nat. Rev. Mol. Cell Biol. 2007;8:275–283. doi: 10.1038/nrm2147.
    1. Maier B., Gluba W., Bernier B., Turner T., Mohammad K., Guise T., Sutherland A., Thorner M., Scrable H. Modulation of mammalian life span by the short isoform of p53. Genes Dev. 2004;18:306–319. doi: 10.1101/gad.1162404.
    1. Tyner S.D., Venkatachalam S., Choi J., Jones S., Ghebranious N., Igelmann H., Lu X., Soron G., Cooper B., Brayton C., et al. p53 mutant mice that display early ageing-associated phenotypes. Nature. 2002;415:45–53. doi: 10.1038/415045a.
    1. Petitjean A., Mathe E., Kato S., Ishioka C., Tavtigian S.V., Hainaut P., Olivier M. Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: Lessons from recent developments in the IARC TP53 database. Hum. Mutat. 2007;28:622–629. doi: 10.1002/humu.20495.
    1. Ochs-Balcom H.M., Marian C., Nie J., Brasky T.M., Goerlitz D.S., Trevisan M., Edge S.B., Winston J., Berry D.L., Kallakury B.V., et al. Adiposity is associated with p53 gene mutations in breast cancer. Breast Cancer Res. Treat. 2015;153:635–645. doi: 10.1007/s10549-015-3570-5.
    1. Minamino T., Orimo M., Shimizu I., Kunieda T., Yokoyama M., Ito T., Nojima A., Nabetani A., Oike Y., Matsubara H., et al. A crucial role for adipose tissue p53 in the regulation of insulin resistance. Nat. Med. 2009;15:1082–1087. doi: 10.1038/nm.2014.
    1. Vergoni B., Cornejo P.J., Gilleron J., Djedaini M., Ceppo F., Jacquel A., Bouget G., Ginet C., Gonzalez T., Maillet J., et al. DNA Damage and the Activation of the p53 Pathway Mediate Alterations in Metabolic and Secretory Functions of Adipocytes. Diabetes. 2016;65:3062–3074. doi: 10.2337/db16-0014.
    1. Hinault C., Kawamori D., Liew C.W., Maier B., Hu J., Keller S.R., Mirmira R.G., Scrable H., Kulkarni R.N. Delta40 Isoform of p53 controls beta-cell proliferation and glucose homeostasis in mice. Diabetes. 2011;60:1210–1222. doi: 10.2337/db09-1379.
    1. Tavana O., Zhu C. Too many breaks (brakes): Pancreatic beta-cell senescence leads to diabetes. Cell Cycle. 2011;10:2471–2484. doi: 10.4161/cc.10.15.16741.
    1. Castro A.V., Kolka C.M., Kim S.P., Bergman R.N. Obesity, insulin resistance and comorbidities? Mechanisms of association. Arq. Bras. Endocrinol. Metabol. 2014;58:600–609. doi: 10.1590/0004-2730000003223.
    1. Al-Aubaidy H.A., Jelinek H.F. Oxidative DNA damage and obesity in type 2 diabetes mellitus. Eur. J. Endocrinol. 2011;164:899–904. doi: 10.1530/EJE-11-0053.
    1. Lee S.C., Chan J.C. Evidence for DNA damage as a biological link between diabetes and cancer. Chin. Med. J. 2015;128:1543–1548. doi: 10.4103/0366-6999.157693.
    1. Zhang Y., Zhou J., Wang T., Cai L. High level glucose increases mutagenesis in human lymphoblastoid cells. Int. J. Biol. Sci. 2007;3:375–379. doi: 10.7150/ijbs.3.375.
    1. Stopper H., Schinzel R., Sebekova K., Heidland A. Genotoxicity of advanced glycation end products in mammalian cells. Cancer Lett. 2003;190:151–156. doi: 10.1016/S0304-3835(02)00626-2.
    1. Fukami K., Yamagishi S., Kaifu K., Matsui T., Kaida Y., Ueda S., Takeuchi M., Asanuma K., Okuda S. Telmisartan inhibits AGE-induced podocyte damage and detachment. Microvasc. Res. 2013;88:79–83. doi: 10.1016/j.mvr.2013.04.006.
    1. Simone S., Gorin Y., Velagapudi C., Abboud H.E., Habib S.L. Mechanism of oxidative DNA damage in diabetes: Tuberin inactivation and downregulation of DNA repair enzyme 8-oxo-7,8-dihydro-2′-deoxyguanosine-DNA glycosylase. Diabetes. 2008;57:2626–2636. doi: 10.2337/db07-1579.
    1. Habib S.L., Liang S. Hyperactivation of Akt/mTOR and deficiency in tuberin increased the oxidative DNA damage in kidney cancer patients with diabetes. Oncotarget. 2014;5:2542–2550. doi: 10.18632/oncotarget.1833.
    1. Xu N., Lao Y., Zhang Y., Gillespie D.A. Akt: A double-edged sword in cell proliferation and genome stability. J. Oncol. 2012;2012:951724. doi: 10.1155/2012/951724.
    1. Habib S.L., Phan M.N., Patel S.K., Li D., Monks T.J., Lau S.S. Reduced constitutive 8-oxoguanine-DNA glycosylase expression and impaired induction following oxidative DNA damage in the tuberin deficient Eker rat. Carcinogenesis. 2003;24:573–582. doi: 10.1093/carcin/24.3.573.
    1. Habib S.L. Molecular mechanism of regulation of OGG1: Tuberin deficiency results in cytoplasmic redistribution of transcriptional factor NF-YA. J. Mol. Signal. 2009;4:8. doi: 10.1186/1750-2187-4-8.
    1. Piscitello D., Varshney D., Lilla S., Vizioli M.G., Reid C., Gorbunova V., Seluanov A., Gillespie D.A., Adams P.D. AKT overactivation can suppress DNA repair via p70S6 kinase-dependent downregulation of MRE11. Oncogene. 2018;37:427–438. doi: 10.1038/onc.2017.340.
    1. Merkel P., Khoury N., Bertolotto C., Perfetti R. Insulin and glucose regulate the expression of the DNA repair enzyme XPD. Mol. Cell Endocrinol. 2003;201:75–85. doi: 10.1016/S0303-7207(02)00432-X.
    1. Komakula S.S.B., Tumova J., Kumaraswamy D., Burchat N., Vartanian V., Ye H., Dobrzyn A., Lloyd R.S., Sampath H. The DNA Repair Protein OGG1 Protects Against Obesity by Altering Mitochondrial Energetics in White Adipose Tissue. Sci. Rep. 2018;8:14886. doi: 10.1038/s41598-018-33151-1.
    1. Dizdaroglu M. Substrate specificities and excision kinetics of DNA glycosylases involved in base-excision repair of oxidative DNA damage. Mutat. Res. 2003;531:109–126. doi: 10.1016/j.mrfmmm.2003.07.003.
    1. Dou H., Mitra S., Hazra T.K. Repair of oxidized bases in DNA bubble structures by human DNA glycosylases NEIL1 and NEIL2. J. Biol. Chem. 2003;278:49679–49684. doi: 10.1074/jbc.M308658200.
    1. Vartanian V., Lowell B., Minko I.G., Wood T.G., Ceci J.D., George S., Ballinger S.W., Corless C.L., McCullough A.K., Lloyd R.S. The metabolic syndrome resulting from a knockout of the NEIL1 DNA glycosylase. Proc. Natl. Acad. Sci. USA. 2006;103:1864–1869. doi: 10.1073/pnas.0507444103.
    1. Sampath H., Vartanian V., Rollins M.R., Sakumi K., Nakabeppu Y., Lloyd R.S. 8-Oxoguanine DNA glycosylase (OGG1) deficiency increases susceptibility to obesity and metabolic dysfunction. PLoS ONE. 2012;7:e51697. doi: 10.1371/journal.pone.0051697.
    1. Bankoglu E.E., Arnold C., Hering I., Hankir M., Seyfried F., Stopper H. Decreased Chromosomal Damage in Lymphocytes of Obese Patients After Bariatric Surgery. Sci. Rep. 2018;8:11195. doi: 10.1038/s41598-018-29581-6.
    1. Gavande N.S., VanderVere-Carozza P.S., Hinshaw H.D., Jalal S.I., Sears C.R., Pawelczak K.S., Turchi J.J. DNA repair targeted therapy: The past or future of cancer treatment? Pharmacol. Ther. 2016;160:65–83. doi: 10.1016/j.pharmthera.2016.02.003.
    1. Turgeon M.O., Perry N.J.S., Poulogiannis G. DNA Damage, Repair, and Cancer Metabolism. Front. Oncol. 2018;8:15. doi: 10.3389/fonc.2018.00015.
    1. Lord C.J., Ashworth A. BRCAness revisited. Nat. Rev. Cancer. 2016;16:110–120. doi: 10.1038/nrc.2015.21.
    1. Chae Y.K., Anker J.F., Carneiro B.A., Chandra S., Kaplan J., Kalyan A., Santa-Maria C.A., Platanias L.C., Giles F.J. Genomic landscape of DNA repair genes in cancer. Oncotarget. 2016;7:23312–23321. doi: 10.18632/oncotarget.8196.
    1. Chan D.S., Vieira A.R., Aune D., Bandera E.V., Greenwood D.C., McTiernan A., Rosenblatt D.N., Thune I., Vieira R., Norat T. Body mass index and survival in women with breast cancer-systematic literature review and meta-analysis of 82 follow-up studies. Ann. Oncol. 2014;25:1901–1914. doi: 10.1093/annonc/mdu042.
    1. Kocarnik J.M., Chan A.T., Slattery M.L., Potter J.D., Meyerhardt J., Phipps A., Nan H., Harrison T., Rohan T.E., Qi L., et al. Relationship of prediagnostic body mass index with survival after colorectal cancer: Stage-specific associations. Int. J. Cancer. 2016;139:1065–1072. doi: 10.1002/ijc.30163.
    1. Nimptsch K., Pischon T. Body fatness, related biomarkers and cancer risk: An epidemiological perspective. Horm. Mol. Biol. Clin. Investig. 2015;22:39–51. doi: 10.1515/hmbci-2014-0043.
    1. Pischon T., Nimptsch K. Obesity and Risk of Cancer: An Introductory Overview. Recent Results Cancer Res. 2016;208:1–15.
    1. Secord A.A., Hasselblad V., von Gruenigen V.E., Gehrig P.A., Modesitt S.C., Bae-Jump V., Havrilesky L.J. Body mass index and mortality in endometrial cancer: A systematic review and meta-analysis. Gynecol. Oncol. 2016;140:184–190. doi: 10.1016/j.ygyno.2015.10.020.
    1. The L. The link between cancer and obesity. Lancet. 2017;390:1716.
    1. Ning Y., Wang L., Giovannucci E.L. A quantitative analysis of body mass index and colorectal cancer: Findings from 56 observational studies. Obes. Rev. 2010;11:19–30. doi: 10.1111/j.1467-789X.2009.00613.x.
    1. Colotta F., Allavena P., Sica A., Garlanda C., Mantovani A. Cancer-related inflammation, the seventh hallmark of cancer: Links to genetic instability. Carcinogenesis. 2009;30:1073–1081. doi: 10.1093/carcin/bgp127.
    1. Fernandez-Sanchez A., Madrigal-Santillan E., Bautista M., Esquivel-Soto J., Morales-Gonzalez A., Esquivel-Chirino C., Durante-Montiel I., Sanchez-Rivera G., Valadez-Vega C., Morales-Gonzalez J.A. Inflammation, oxidative stress, and obesity. Int. J. Mol. Sci. 2011;12:3117–3132. doi: 10.3390/ijms12053117.
    1. Jung U.J., Choi M.S. Obesity and its metabolic complications: The role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int. J. Mol. Sci. 2014;15:6184–6223. doi: 10.3390/ijms15046184.
    1. Sun B., Karin M. Obesity, inflammation, and liver cancer. J. Hepatol. 2012;56:704–713. doi: 10.1016/j.jhep.2011.09.020.
    1. Ramos-Nino M.E. The role of chronic inflammation in obesity-associated cancers. ISRN Oncol. 2013;2013:697521. doi: 10.1155/2013/697521.
    1. Riondino S., Roselli M., Palmirotta R., Della-Morte D., Ferroni P., Guadagni F. Obesity and colorectal cancer: Role of adipokines in tumor initiation and progression. World J. Gastroenterol. 2014;20:5177–5190. doi: 10.3748/wjg.v20.i18.5177.
    1. Otani K., Ishihara S., Yamaguchi H., Murono K., Yasuda K., Nishikawa T., Tanaka T., Kiyomatsu T., Hata K., Kawai K., et al. Adiponectin and colorectal cancer. Surg. Today. 2017;47:151–158. doi: 10.1007/s00595-016-1334-4.
    1. Barb D., Pazaitou-Panayiotou K., Mantzoros C.S. Adiponectin: A link between obesity and cancer. Expert Opin. Investig. Drugs. 2006;15:917–931. doi: 10.1517/13543784.15.8.917.
    1. Stattin P., Lukanova A., Biessy C., Soderberg S., Palmqvist R., Kaaks R., Olsson T., Jellum E. Obesity and colon cancer: Does leptin provide a link? Int. J. Cancer. 2004;109:149–152. doi: 10.1002/ijc.11668.
    1. Stattin P., Palmqvist R., Soderberg S., Biessy C., Ardnor B., Hallmans G., Kaaks R., Olsson T. Plasma leptin and colorectal cancer risk: A prospective study in Northern Sweden. Oncol. Rep. 2003;10:2015–2021. doi: 10.3892/or.10.6.2015.
    1. Orecchioni S., Reggiani F., Talarico G., Bertolini F. Mechanisms of obesity in the development of breast cancer. Discov. Med. 2015;20:121–128.
    1. Karin M., Greten F.R. NF-kappaB: Linking inflammation and immunity to cancer development and progression. Nat. Rev. Immunol. 2005;5:749–759. doi: 10.1038/nri1703.
    1. McCool K.W., Miyamoto S. DNA damage-dependent NF-kappaB activation: NEMO turns nuclear signaling inside out. Immunol. Rev. 2012;246:311–326. doi: 10.1111/j.1600-065X.2012.01101.x.
    1. Wang W., Mani A.M., Wu Z.H. DNA damage-induced nuclear factor-kappa B activation and its roles in cancer progression. J. Cancer Metastasis Treat. 2017;3:45–59. doi: 10.20517/2394-4722.2017.03.
    1. Valentino E., Bellazzo A., di Minin G., Sicari D., Apollonio M., Scognamiglio G., di Bonito M., Botti G., del Sal G., Collavin L. Mutant p53 potentiates the oncogenic effects of insulin by inhibiting the tumor suppressor DAB2IP. Proc. Natl. Acad. Sci. USA. 2017;114:7623–7628. doi: 10.1073/pnas.1700996114.
    1. Hanahan D., Weinberg R.A. Hallmarks of cancer: The next generation. Cell. 2011;144:646–674. doi: 10.1016/j.cell.2011.02.013.
    1. Macheda M.L., Rogers S., Best J.D. Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer. J. Cell Physiol. 2005;202:654–662. doi: 10.1002/jcp.20166.
    1. Koppenol W.H., Bounds P.L., Dang C.V. Otto Warburg’s contributions to current concepts of cancer metabolism. Nat. Rev. Cancer. 2011;11:325–337. doi: 10.1038/nrc3038.
    1. Levine A.J., Puzio-Kuter A.M. The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes. Science. 2010;330:1340–1344. doi: 10.1126/science.1193494.
    1. Rose D.P., Gracheck P.J., Vona-Davis L. The Interactions of Obesity, Inflammation and Insulin Resistance in Breast Cancer. Cancers. 2015;7:2147–2168. doi: 10.3390/cancers7040883.
    1. Marnett L.J. Chemistry and biology of DNA damage by malondialdehyde. IARC Sci. Publ. 1999;150:17–27.
    1. Voulgaridou G.P., Anestopoulos I., Franco R., Panayiotidis M.I., Pappa A. DNA damage induced by endogenous aldehydes: Current state of knowledge. Mutat. Res. 2011;711:13–27. doi: 10.1016/j.mrfmmm.2011.03.006.
    1. Wen C., Wu L., Fu L., Wang B., Zhou H. Unifying mechanism in the initiation of breast cancer by metabolism of estrogen (Review) Mol. Med. Rep. 2017;16:1001–1006. doi: 10.3892/mmr.2017.6738.
    1. Fussell K.C., Udasin R.G., Smith P.J., Gallo M.A., Laskin J.D. Catechol metabolites of endogenous estrogens induce redox cycling and generate reactive oxygen species in breast epithelial cells. Carcinogenesis. 2011;32:1285–1293. doi: 10.1093/carcin/bgr109.
    1. Yager J.D., Liehr J.G. Molecular mechanisms of estrogen carcinogenesis. Annu. Rev. Pharmacol. Toxicol. 1996;36:203–232. doi: 10.1146/annurev.pa.36.040196.001223.
    1. Yasuda M.T., Sakakibara H., Shimoi K. Estrogen- and stress-induced DNA damage in breast cancer and chemoprevention with dietary flavonoid. Genes Environ. 2017;39:10. doi: 10.1186/s41021-016-0071-7.
    1. Caldon C.E. Estrogen signaling and the DNA damage response in hormone dependent breast cancers. Front. Oncol. 2014;4:106. doi: 10.3389/fonc.2014.00106.
    1. Wysham W.Z., Mhawech-Fauceglia P., Li H., Hays L., Syriac S., Skrepnik T., Wright J., Pande N., Hoatlin M., Pejovic T. BRCAness profile of sporadic ovarian cancer predicts disease recurrence. PLoS ONE. 2012;7:e30042. doi: 10.1371/journal.pone.0030042.
    1. Mhawech-Fauceglia P., Wang D., Kim G., Sharifian M., Chen X., Liu Q., Lin Y.G., Liu S., Pejovic T. Expression of DNA repair proteins in endometrial cancer predicts disease outcome. Gynecol. Oncol. 2014;132:593–598. doi: 10.1016/j.ygyno.2014.02.002.
    1. Godoy H., Mhawech-Fauceglia P., Beck A., Miller A., Lele S., Odunsi K. Expression of poly (adenosine diphosphate-ribose) polymerase and p53 in epithelial ovarian cancer and their role in prognosis and disease outcome. Int. J. Gynecol. Pathol. 2011;30:139–144. doi: 10.1097/PGP.0b013e3181fa5a64.

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