Skip to main content

Advertisement

Log in

Childhood Obesity and Cancer Risk in Adulthood

  • Metabolism (M Dalamaga, Section Editor)
  • Published:
Current Obesity Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The purpose of this review is to summarize our current understanding of the association between childhood obesity and cancer risk later in life.

Recent Findings

Adipose tissue secrets a variety of adipocytokines, and expression and/or secretion rate of most of them seems to be increased or dysregulated in obesity. In addition, obesity leads to increased secretion of proinflammatory cytokines such as interferon-γ (IFN-γ), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α), which promotes an infiltration of inflammatory immune cells into adipose tissue. This process may facilitate a state of “subclinical inflammation” (metaflammation) and may lead to the development of the metabolic syndrome (MetS), starting as early as during childhood. In addition, several oncogenes have been linked to inflammation and cancer development via different pathways, and several types of tumors need an inflammatory environment before a malignant change occurs. An inflammatory environment seems to promote the proliferation and survival of malignant cells as well as angiogenesis. Natural killer (NK) cells play an important role in this process, as they are able to kill transformed cells without prior sensitization and coordinate subsequent immune responses by producing distinct cytokines, thus providing antitumor immunity. First studies in children have suggested that NK cells from obese children are activated, metabolically stressed, and functionally deficient. This may lead to a suppression of antitumor immunity as early as during childhood, probably many years before the development of cancer.

Summary

Epidemiological studies have shown a strong association between higher body mass index (BMI) during childhood and adolescence and increased risk for several malignancies in adulthood, including leukemia, Hodgkin’s disease, colorectal cancer, and breast cancer. Underlying mechanisms are not completely understood, but several adipocytokines and inflammatory markers including NK cells seem to be “key players” in this process.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Forouzanfar MH, Afshin A, Alexander LT, Anderson HR, Bhutta ZA, Biryukov S, et al. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. The Lancet. 2016;388(10053):1659–724.

    Google Scholar 

  2. Global Burden of Disease Study Collaborators, Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, et al. Health effects of overweight and obesity in 195 countries over 25 years. The New England Journal of Medicine. 2017;377(1):13–27 The worldwide development and prevalence of obesity among children and adolescents during the past 25 years has been analyzed. The paper underlines the importance of a global strategy against childhood obesity.

    Google Scholar 

  3. Weihrauch-Blüher S, Schwarz P, Klusmann J-H. Childhood obesity: increased risk for cardiometabolic disease and cancer in adulthood. Metabolism. 2019;92:147–52.

    PubMed  Google Scholar 

  4. World Health O Cancer attributable to obesity 2012 [Available from: https://gco.iarc.fr/causes/obesity/tools-map.

  5. Brown KF, Rumgay H, Dunlop C, Ryan M, Quartly F, Cox A, et al. The fraction of cancer attributable to modifiable risk factors in England, Wales, Scotland, Northern Ireland, and the United Kingdom in 2015. British Journal of Cancer. 2018;118(8):1130–41.

    PubMed  PubMed Central  Google Scholar 

  6. Arnold M, Pandeya N, Byrnes G, Renehan PAG, Stevens GA, Ezzati PM, et al. Global burden of cancer attributable to high body-mass index in 2012: a population-based study. Lancet Oncol. 2015;16(1):36–46.

    PubMed  Google Scholar 

  7. Biro FM, Wien M. Childhood obesity and adult morbidities. The American Journal of Clinical Nutrition. 2010;91(5):1499S–505S.

    PubMed  PubMed Central  Google Scholar 

  8. Aarestrup J, Gamborg M, Ulrich LG, Sørensen TIA, Baker JL. Childhood body mass index and height and risk of histologic subtypes of endometrial. Cancer. 2016;40(7):1096–102.

    CAS  Google Scholar 

  9. Jensen BW, Gamborg M, Gögenur I, Renehan AG, Sørensen TIA, Baker JL. Childhood body mass index and height in relation to site-specific risks of colorectal cancers in adult life. European Journal of Epidemiology. 2017;32(12):1097–106.

    CAS  PubMed  Google Scholar 

  10. Farooqi IS, O’Rahilly S. Genetics of obesity in humans. Endocrine Reviews. 2006;27(7):710–8.

    CAS  PubMed  Google Scholar 

  11. Mamun AA, Mannan M, Doi SAR. Gestational weight gain in relation to offspring obesity over the life course: a systematic review and bias-adjusted meta-analysis. Obesity Reviews. 2014;15(4):338–47.

    CAS  PubMed  Google Scholar 

  12. Rayfield S, Plugge E. Systematic review and meta-analysis of the association between maternal smoking in pregnancy and childhood overweight and obesity. Journal of Epidemiology and Community Health. 2017;71(2):162–73.

    PubMed  Google Scholar 

  13. Vidakovic AJ, Gishti O, Voortman T, Felix JF, Williams MA, Hofman A, et al. Maternal plasma PUFA concentrations during pregnancy and childhood adiposity: the Generation R Study. The American Journal of Clinical Nutrition. 2016;103(4):1017–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Mudd LM, Pivarnik JM, Pfeiffer KA, Paneth N, Chung H, Holzman C. Maternal physical activity during pregnancy, child leisure-time activity, and child weight status at 3 to 9 years. 2015;12(4):506.

  15. Yuan C, Gaskins AJ, Blaine AI, Zhang C, Gillman MW, Missmer SA, et al. Association between cesarean birth and risk of obesity in offspring in childhood, adolescence, and early adulthood. JAMA Pediatrics. 2016;170(11):e162385-e.

    Google Scholar 

  16. Victora CG, Bahl R, Barros AJD, França GVA, Horton S, Krasevec J, et al. Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect. The Lancet. 2016;387(10017):475–90.

    Google Scholar 

  17. Khan MJ, Gerasimidis K, Edwards CA, Shaikh MG. Role of gut microbiota in the aetiology of obesity: proposed mechanisms and review of the literature. Journal of Obesity. 2016;2016:7353642.

    PubMed  PubMed Central  Google Scholar 

  18. Stanislawski MA, Dabelea D, Wagner BD, Iszatt N, Dahl C, Sontag MK, et al. Gut microbiota in the first 2 years of life and the association with body mass index at age 12 in a Norwegian birth cohort. mBio. 2018;9(5).

  19. Swinburn BA, Sacks G, Hall KD, McPherson K, Finegood DT, Moodie ML, et al. The global obesity pandemic: shaped by global drivers and local environments. Lancet. 2011;378(9793):804–14.

    PubMed  Google Scholar 

  20. Esteve RM. Adipose tissue: cell heterogeneity and functional diversity. Endocrinol Nutr. 2014;61(2):100–12.

    Google Scholar 

  21. Francisco V, Pino J, Gonzalez-Gay MA, Mera A, Lago F, Gomez R, et al. Adipokines and inflammation: is it a question of weight? Br J Pharmacol. 2018;175(10):1569–79.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Francisco V, Pino J, Campos-Cabaleiro V, Ruiz-Fernandez C, Mera A, Gonzalez-Gay MA, et al. Obesity, fat mass and immune system: role for leptin. Front Physiol. 2018;9:640.

    PubMed  PubMed Central  Google Scholar 

  23. Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity. Annu Rev Immunol. 2011;29:415–45.

    CAS  PubMed  Google Scholar 

  24. Wensveen FM, Jelencic V, Valentic S, Sestan M, Wensveen TT, Theurich S, et al. NK cells link obesity-induced adipose stress to inflammation and insulin resistance. Nat Immunol. 2015;16(4):376–85.

    CAS  PubMed  Google Scholar 

  25. Castoldi A, de Naffah Souza C, Camara NO, Moraes-Vieira PM. The macrophage switch in obesity development. Front Immunol. 2015;6:637.

    PubMed  Google Scholar 

  26. Gerriets VA, MacIver NJ. Role of T cells in malnutrition and obesity. Front Immunol. 2014;5:379.

    PubMed  PubMed Central  Google Scholar 

  27. Nave H, Mueller G, Siegmund B, Jacobs R, Stroh T, Schueler U, et al. Resistance of Janus kinase-2 dependent leptin signaling in natural killer (NK) cells: a novel mechanism of NK cell dysfunction in diet-induced obesity. Endocrinology. 2008;149(7):3370–8.

    CAS  PubMed  Google Scholar 

  28. O’Shea D, Cawood TJ, O’Farrelly C, Lynch L. Natural killer cells in obesity: impaired function and increased susceptibility to the effects of cigarette smoke. PLoS One. 2010;5(1):e8660.

    PubMed  PubMed Central  Google Scholar 

  29. Laue T, Wrann CD, Hoffmann-Castendiek B, Pietsch D, Hubner L, Kielstein H. Altered NK cell function in obese healthy humans. BMC Obes. 2015;2:1.

    PubMed  PubMed Central  Google Scholar 

  30. Viel S, Besson L, Charrier E, Marcais A, Disse E, Bienvenu J, et al. Alteration of Natural Killer cell phenotype and function in obese individuals. Clin Immunol. 2017;177:12–7.

    CAS  PubMed  Google Scholar 

  31. Rodriguez-Hernandez H, Simental-Mendia LE, Rodriguez-Ramirez G, Reyes-Romero MA. Obesity and inflammation: epidemiology, risk factors, and markers of inflammation. Int J Endocrinol. 2013;2013:678159.

    PubMed  PubMed Central  Google Scholar 

  32. Liu R, Nikolajczyk BS. Tissue immune cells fuel obesity-associated inflammation in adipose tissue and beyond. Front Immunol. 2019;10:1587.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Singer K, Lumeng CN. The initiation of metabolic inflammation in childhood obesity. J Clin Invest. 2017;127(1):65–73 In this review, the initiating events of metaflammation during childhood obesity and mechanisms transferring effects into adulthood are comprehensively discussed.

    PubMed  PubMed Central  Google Scholar 

  34. Berger NA. Obesity and cancer pathogenesis. Ann N Y Acad Sci. 2014;1311:57–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Ackerman SE, Blackburn OA, Marchildon F, Cohen P. Insights into the link between obesity and cancer. Curr Obes Rep. 2017;6(2):195–203.

    PubMed  Google Scholar 

  36. Himbert C, Delphan M, Scherer D, Bowers LW, Hursting S, Ulrich CM. Signals from the adipose microenvironment and the obesity-cancer link-a systematic review. Cancer Prev Res (Phila). 2017;10(9):494–506.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Morris PG, Hudis CA, Giri D, Morrow M, Falcone DJ, Zhou XK, et al. Inflammation and increased aromatase expression occur in the breast tissue of obese women with breast cancer. Cancer Prev Res (Phila). 2011;4(7):1021–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Rossi EL, de Angel RE, Bowers LW, Khatib SA, Smith LA, Van Buren E, et al. Obesity-associated alterations in inflammation, epigenetics, and mammary tumor growth persist in formerly obese mice. Cancer Prev Res (Phila). 2016;9(5):339–48.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, Lanier LL, et al. Innate or adaptive immunity? The example of natural killer cells. Science. 2011;331(6013):44–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Tomasello E, Blery M, Vely F, Vivier E. Signaling pathways engaged by NK cell receptors: double concerto for activating receptors, inhibitory receptors and NK cells. Semin Immunol. 2000;12(2):139–47.

    CAS  PubMed  Google Scholar 

  41. Wrann CD, Laue T, Hubner L, Kuhlmann S, Jacobs R, Goudeva L, et al. Short-term and long-term leptin exposure differentially affect human natural killer cell immune functions. Am J Physiol Endocrinol Metab. 2012;302(1):E108–16.

    CAS  PubMed  Google Scholar 

  42. Bahr I, Jahn J, Zipprich A, Pahlow I, Spielmann J, Kielstein H. Impaired natural killer cell subset phenotypes in human obesity. Immunol Res. 2018;66(2):234–44.

    PubMed  PubMed Central  Google Scholar 

  43. Bahr I, Goritz V, Doberstein H, Hiller GG, Rosenstock P, Jahn J, et al. Diet-induced obesity is associated with an impaired NK cell function and an increased colon cancer incidence. J Nutr Metab. 2017;2017:4297025.

    PubMed  PubMed Central  Google Scholar 

  44. Spielmann J, Hanke J, Knauf D, Ben-Eliyahu S, Jacobs R, Stangl GI, et al. Significantly enhanced lung metastasis and reduced organ NK cell functions in diet-induced obese rats. BMC Obes. 2017;4:24.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Moulin CM, Marguti I, Peron JP, Halpern A, Rizzo LV. Bariatric surgery reverses natural killer (NK) cell activity and NK-related cytokine synthesis impairment induced by morbid obesity. Obes Surg. 2011;21(1):112–8.

    PubMed  Google Scholar 

  46. Jahn J, Spielau M, Brandsch C, Stangl GI, Delank KS, Bahr I, et al. Decreased NK cell functions in obesity can be reactivated by fat mass reduction. Obesity (Silver Spring). 2015;23(11):2233–41.

    CAS  Google Scholar 

  47. Federico A, D’Aiuto E, Borriello F, Barra G, Gravina AG, Romano M, et al. Fat: a matter of disturbance for the immune system. World J Gastroenterol. 2010;16(38):4762–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Cildir G, Akincilar SC, Tergaonkar V. Chronic adipose tissue inflammation: all immune cells on the stage. Trends Mol Med. 2013;19(8):487–500.

    CAS  PubMed  Google Scholar 

  49. Tobin LM, Mavinkurve M, Carolan E, Kinlen D, O’Brien EC, Little MA, et al. NK cells in childhood obesity are activated, metabolically stressed, and functionally deficient. JCI Insight. 2017;2(24). This study revealed for the first time a potential role of NK cells in childhood obesity and metaflammation, i.e., impaired NK function in childhood obesity.

  50. (WCRF) WCRF. Cancer statistics [Available from: https://www.wcrf-uk.org/uk/preventing-cancer/what-can-increase-your-risk-cancer/obesity-weight-and-cancer-risk.

  51. Renehan AG, Soerjomataram I, Tyson M, Egger M, Zwahlen M, Coebergh JW, et al. Incident cancer burden attributable to excess body mass index in 30 European countries. 2010;126(3):692–702. Int J Cancer. 2010 Feb 1;126(3):692–702.

    CAS  PubMed  Google Scholar 

  52. Anderson AS, Key TJ, Norat T, Scoccianti C, Cecchini M, Berrino F, et al. European code against cancer 4th edition: Obesity, body fatness and cancer. Cancer Epidemiol. 2015;39(Suppl 1):S34–45.

    PubMed  Google Scholar 

  53. Blüher S, Schwarz P. Metabolically healthy obesity from childhood to adulthood — does weight status alone matter? Metabolism. 2014;63(9):1084–92.

    PubMed  Google Scholar 

  54. Bluher S, Panagiotou G, Petroff D, Markert J, Wagner A, Klemm T, et al. Effects of a 1-year exercise and lifestyle intervention on irisin, adipokines, and inflammatory markers in obese children. Obesity (Silver Spring). 2014;22(7):1701–8.

    Google Scholar 

  55. Jeffreys M, Smith GD, Martin RM, Frankel S, Gunnell D. Childhood body mass index and later cancer risk: a 50-year follow-up of the Boyd Orr study. Int J Cancer. 2004;112(2):348–51.

    CAS  PubMed  Google Scholar 

  56. Berger NA. Young adult cancer: influence of the obesity pandemic. Obesity (Silver Spring). 2018;26(4):641–50.

    PubMed Central  Google Scholar 

  57. Lee JE, Nam CM, Lee SG, Park S, Kim TH, Park EC. The economic burden of cancer attributable to obesity in Korea: a population-based cohort study. European Journal of Cancer Care. 2019;28(5).

  58. Bähr I, Spielmann J, Quandt D, Kielstein H. Obesity-associated alterations of natural killer cells and immunosurveillance of cancer. Front Immunol. 2020;11(245). https://doi.org/10.3389/immu2020.00245This review summarizes data from animal and human studies showing the alterations found in NK cells associated with obesity and their potential impact on obesity-associated diseases. Moreover, the effects of physical activity, nutritional factors, and the reduction of body weight and fat mass on NK cell functions of obese individuals are reviewed.

  59. Perez-Cornago A, Appleby PN, Pischon T, Tsilidis KK, Tjonneland A, Olsen A, et al. Tall height and obesity are associated with an increased risk of aggressive prostate cancer: results from the EPIC cohort study. BMC Med. 2017;15(1):115.

    PubMed  PubMed Central  Google Scholar 

  60. Weiss R, Dziura J, Burgert TS, Tamborlane WV, Taksali SE, Yeckel CW, et al. Obesity and the metabolic syndrome in children and adolescents. The New England journal of medicine. 2004;350(23):2362–74.

    CAS  PubMed  Google Scholar 

  61. Smith AG, Sheridan PA, Harp JB, Beck MA. Diet-induced obese mice have increased mortality and altered immune responses when infected with influenza virus. J Nutr. 2007;137(5):1236–43.

    CAS  PubMed  Google Scholar 

  62. Sutherland JP, McKinley B, Eckel RH. The metabolic syndrome and inflammation. Metab Syndr Relat Disord. 2004;2(2):82–104.

    CAS  PubMed  Google Scholar 

  63. Park MH, Falconer C, Viner RM, Kinra S. The impact of childhood obesity on morbidity and mortality in adulthood: a systematic review. Obes Rev. 2012;13(11):985–1000.

    CAS  PubMed  Google Scholar 

  64. Levi Z, Kark JD, Barchana M, Liphshitz I, Zavdi O, Tzur D, et al. Measured body mass index in adolescence and the incidence of colorectal cancer in a cohort of 1.1 million males. Cancer Epidemiol Biomarkers Prev. 2011;20(12):2524–31.

    PubMed  Google Scholar 

  65. Levi Z, Kark JD, Afek A, Derazne E, Tzur D, Furman M, et al. Measured body mass index in adolescence and the incidence of pancreatic cancer in a cohort of 720,000 Jewish men. Cancer Causes Control. 2012;23(2):371–8.

    PubMed  Google Scholar 

  66. Leiba A, Kark JD, Afek A, Derazne E, Barchana M, Tzur D, et al. Adolescent obesity and paternal country of origin predict renal cell carcinoma: a cohort study of 1.1 million 16 to 19-year-old males. J Urol. 2013;189(1):25–9.

    PubMed  Google Scholar 

  67. Levi Z, Kark JD, Shamiss A, Derazne E, Tzur D, Keinan-Boker L, et al. Body mass index and socioeconomic status measured in adolescence, country of origin, and the incidence of gastroesophageal adenocarcinoma in a cohort of 1 million men. Cancer. 2013;119(23):4086–93.

    PubMed  Google Scholar 

  68. Leiba M, Leiba A, Keinan-Boker L, Avigdor A, Derazne E, Levine H, et al. Adolescent weight and height are predictors of specific non-Hodgkin lymphoma subtypes among a cohort of 2,352,988 individuals aged 16 to 19 years. Cancer. 2016;122(7):1068–77.

    PubMed  Google Scholar 

  69. Shamriz O, Leiba M, Levine H, Derazne E, Keinan-Boker L, Kark JD. Higher body mass index in 16–19 year-old Jewish adolescents of North African, Middle Eastern and European origins is a predictor of acute myeloid leukemia: a cohort of 2.3 million Israelis. Cancer Causes & Control. 2017;28(4):331–9.

    Google Scholar 

  70. Poynter JN, Richardson M, Blair CK, Roesler MA, Hirsch BA, Nguyen P, et al. Obesity over the life course and risk of acute myeloid leukemia and myelodysplastic syndromes. Cancer Epidemiol. 2016;40:134–40.

    PubMed  Google Scholar 

  71. Shade ED, Ulrich CM, Wener MH, Wood B, Yasui Y, Lacroix K, et al. Frequent intentional weight loss is associated with lower natural killer cell cytotoxicity in postmenopausal women: possible long-term immune effects. J Am Diet Assoc. 2004;104(6):903–12.

    PubMed  Google Scholar 

  72. Chang H-H, Moro A, Takakura K, Su H-Y, Mo A, Nakanishi M, et al. Incidence of pancreatic cancer is dramatically increased by a high fat, high calorie diet in KrasG12D mice. PloS one. 2017;12(9):e0184455-e.

    Google Scholar 

  73. Doerner SK, Reis ES, Leung ES, Ko JS, Heaney JD, Berger NA, et al. High-fat diet-induced complement activation mediates intestinal inflammation and neoplasia, independent of obesity. Mol Cancer Res. 2016;14(10):953–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Moley KH, Colditz GA. Effects of obesity on hormonally driven cancer in women. Sci Transl Med. 2016;8(323):323ps3.

    PubMed  PubMed Central  Google Scholar 

  75. Liu Y, Metzinger MN, Lewellen KA, Cripps SN, Carey KD, Harper EI, et al. Obesity contributes to ovarian cancer metastatic success through increased lipogenesis, enhanced vascularity, and decreased infiltration of M1 macrophages. Cancer Res. 2015;75(23):5046–57.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Susann Weihrauch-Blüher.

Ethics declarations

Conflict of Interest

The authors do not have any conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Metabolism

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Weihe, P., Spielmann, J., Kielstein, H. et al. Childhood Obesity and Cancer Risk in Adulthood. Curr Obes Rep 9, 204–212 (2020). https://doi.org/10.1007/s13679-020-00387-w

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13679-020-00387-w

Keywords

Navigation