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The Obesity Paradox in Cancer: Epidemiologic Insights and Perspectives

  • Cancer (MF Leitzmann, Section Editor)
  • Published:
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Abstract

Purpose of Review

Controversy exists whether excess body fatness (measured by body mass index (BMI)) is associated with better cancer survival (“obesity paradox”). Here, we review the obesity paradox in cancer research and discuss potential explanations and future research directions.

Recent Findings

Overweight and obese cancer patients have better survival for diverse cancers. This apparent obesity paradox may be largely explained by methodological limitations including reverse causation, selection bias, confounding, and reliance of BMI as a measure of adiposity in cancer patients. A growing number of studies show promising evidence that precisely quantified body composition can provide important prognostic information in cancer care, such that low muscle and high adiposity are associated with worse clinical outcomes in cancer patients.

Summary

The term obesity paradox in cancer, implying a causally beneficial role of adiposity, is misleading. Understanding the role of muscle and adiposity may reduce the confusion and inform precision oncology care.

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References

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

  1. World Cancer Research Fund/American Institute for Cancer Research. Diet, Nutrition, physical activity and cancer: a global perspective. continuous update project expert report 2018. Available at http://www.dietandcancerreport.org.

  2. World Cancer Research Fund International: continuous update project report: food, nutrition, physical activity, and the prevention of cancer. http://www.wcrf.org/int/research-we-fund/continuous-update-project-cup. Accessed 1 Apr 2019

  3. Lennon H, Sperrin M, Badrick E, Renehan AG. The obesity paradox in cancer: a review. Curr Oncol Rep. 2016;18(9):56.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Lainscak M, von Haehling S, Doehner W, Anker SD. The obesity paradox in chronic disease: facts and numbers. J Cachexia Sarcopenia Muscle. 2012;3(1):1–4.

    Article  PubMed  PubMed Central  Google Scholar 

  5. •• Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K, et al. Body fatness and cancer--viewpoint of the IARC Working Group. N Engl J Med. 2016;375(8):794–8. https://doi.org/10.1056/NEJMsr1606602 This report concluded that the absence of excess fat can prevent 13 types of cancers.

    Article  PubMed  Google Scholar 

  6. Kyrgiou M, Kalliala I, Markozannes G, Gunter MJ, Paraskevaidis E, Gabra H, et al. Adiposity and cancer at major anatomical sites: umbrella review of the literature. Bmj. 2017;356:j477.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Kayani B, Okabayashi K, Ashrafian H, Harling L, Rao C, Darzi A, et al. Does obesity affect outcomes in patients undergoing esophagectomy for cancer? A meta-analysis. World J Surg. 2012;36(8):1785–95.

    Article  PubMed  Google Scholar 

  8. Zhang X, Liu Y, Shao H, Zheng X. Obesity paradox in lung cancer prognosis: evolving biological insights and clinical implications. J Thorac Oncol. 2017;12(10):1478–88.

    Article  PubMed  Google Scholar 

  9. Li S, Wang Z, Huang J, Fan J, Du H, Liu L, et al. Systematic review of prognostic roles of body mass index for patients undergoing lung cancer surgery: does the ‘obesity paradox’ really exist? Eur J Cardiothorac Surg. 2017;51(5):817–28.

    PubMed  Google Scholar 

  10. Schlesinger S, Siegert S, Koch M, Walter J, Heits N, Hinz S, et al. Postdiagnosis body mass index and risk of mortality in colorectal cancer survivors: a prospective study and meta-analysis. Cancer Causes Control. 2014;25(10):1407–18.

    Article  PubMed  Google Scholar 

  11. Choi Y, Park B, Jeong BC, Seo SI, Jeon SS, Choi HY, et al. Body mass index and survival in patients with renal cell carcinoma: a clinical-based cohort and meta-analysis. Int J Cancer. 2013;132(3):625–34.

    Article  CAS  PubMed  Google Scholar 

  12. Stiles ZE, Rist TM, Dickson PV, Glazer ES, Fleming MD, Shibata D, et al. Impact of body mass index on the short-term outcomes of resected gastrointestinal stromal tumors. J Surg Res. 2017;217:123–30.

    Article  PubMed  Google Scholar 

  13. Brunner AM, Sadrzadeh H, Feng Y, Drapkin BJ, Ballen KK, Attar EC, et al. Association between baseline body mass index and overall survival among patients over age 60 with acute myeloid leukemia. Am J Hematol. 2013;88(8):642–6.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Carson KR, Bartlett NL, McDonald JR, Luo S, Zeringue A, Liu J, et al. Increased body mass index is associated with improved survival in United States veterans with diffuse large B-cell lymphoma. J Clin Oncol. 2012;30(26):3217–22.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Weiss L, Melchardt T, Habringer S, Boekstegers A, Hufnagl C, Neureiter D, et al. Increased body mass index is associated with improved overall survival in diffuse large B-cell lymphoma. Ann Oncol. 2013;25(1):171–6.

    Article  PubMed  Google Scholar 

  16. Westhoff E, Witjes JA, Fleshner NE, Lerner SP, Shariat SF, Steineck G, et al. Body mass index, diet-related factors, and bladder cancer prognosis: a systematic review and meta-analysis. Bladder Cancer. 2018;4(1):91–112.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Farris MS, Courneya KS, Kopciuk KA, McGregor SE, Friedenreich CM. Anthropometric measurements and survival after a prostate cancer diagnosis. Br J Cancer. 2018;118(4):607–10.

    Article  PubMed  Google Scholar 

  18. Secord AA, Hasselblad V, Von Gruenigen VE, Gehrig PA, Modesitt SC, Bae-Jump V, et al. Body mass index and mortality in endometrial cancer: a systematic review and meta-analysis. Gynecol Oncol. 2016;140(1):184–90.

    Article  PubMed  Google Scholar 

  19. Chan D, Vieira A, Aune D, Bandera E, Greenwood D, McTiernan A, et al. 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(10):1901–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Jiralerspong S, Goodwin PJ. Obesity and breast cancer prognosis: evidence, challenges, and opportunities. J Clin Oncol. 2016;34(35):4203–16.

    Article  CAS  PubMed  Google Scholar 

  21. Protani MM, Nagle CM, Webb PM. Obesity and ovarian cancer survival: a systematic review and meta-analysis. Cancer Prev Res. 2012;5(7):901–10.

    Article  Google Scholar 

  22. Greenlee H, Unger JM, LeBlanc M, Ramsey S, Hershman DL. Association between body mass index and cancer survival in a pooled analysis of 22 clinical trials. AACR. 2017.

  23. Chiolero A, Faeh D, Paccaud F, Cornuz J. Consequences of smoking for body weight, body fat distribution, and insulin resistance. Am J Clin Nutr. 2008;87(4):801–9.

    Article  CAS  PubMed  Google Scholar 

  24. Smith L, Brinton LA, Spitz MR, Lam TK, Park Y, Hollenbeck AR, et al. Body mass index and risk of lung cancer among never, former, and current smokers. J Natl Cancer Inst. 2012;104(10):778–89.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Gao C, Patel CJ, Michailidou K, Peters U, Gong J, Schildkraut J, et al. Mendelian randomization study of adiposity-related traits and risk of breast, ovarian, prostate, lung and colorectal cancer. Int J Epidemiol. 2016:dyw129.

  26. Carreras-Torres R, Johansson M, Haycock PC, Wade KH, Relton CL, Martin RM, et al. Obesity, metabolic factors and risk of different histological types of lung cancer: a Mendelian randomization study. PLoS One. 2017;12(6):e0177875.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Song M, Giovannucci E. Estimating the influence of obesity on cancer risk: stratification by smoking is critical. J Clin Oncol. 2016;34(27):3237–9.

    Article  PubMed  Google Scholar 

  28. Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011;12(5):489–95.

    Article  Google Scholar 

  29. Bruggeman AR, Kamal AH, LeBlanc TW, Ma JD, Baracos VE, Roeland EJ. Cancer cachexia: beyond weight loss. J Oncol Pract. 2016;12(11):1163–71.

    Article  PubMed  Google Scholar 

  30. Meyerhardt JA, Kroenke CH, Prado CM, Kwan ML, Castillo A, Weltzien E et al. Association of weight change after colorectal cancer diagnosis and outcomes in the Kaiser Permanente Northern California Population. Cancer Epidemiol Biomarkers Prev. 2017;26(1):30-7.

  31. Feliciano EMC, Kroenke CH, Bradshaw PT, Chen WY, Prado CM, Weltzien EK et al. Postdiagnosis weight change and survival following a diagnosis of early-stage breast cancer. Cancer Epidemiol Biomarkers Prev. 2017;26(1):44-50.

  32. Hernán MA, Hernández-Díaz S, Robins JM. A structural approach to selection bias. Epidemiology. 2004;15(5):615–25.

    Article  PubMed  Google Scholar 

  33. Banack HR, Kaufman JS. The “obesity paradox” explained. Epidemiology. 2013;24(3):461–2.

    Article  PubMed  Google Scholar 

  34. Banack HR, Kaufman JS. From bad to worse: collider stratification amplifies confounding bias in the “obesity paradox”. Eur J Epidemiol. 2015;30(10):1111–4.

    Article  PubMed  Google Scholar 

  35. Banack HR, Kaufman JS. Does selection bias explain the obesity paradox among individuals with cardiovascular disease? Ann Epidemiol. 2015;25(5):342–9.

    Article  PubMed  Google Scholar 

  36. Sperrin M, Candlish J, Badrick E, Renehan A, Buchan I. Collider bias is only a partial explanation for the obesity paradox. Epidemiology (Cambridge, Mass). 2016;27(4):525–30.

    Article  Google Scholar 

  37. Visscher TL, Seidell JC, Molarius A, van der Kuip D, Hofman A, Witteman JC. A comparison of body mass index, waist-hip ratio and waist circumference as predictors of all-cause mortality among the elderly: the Rotterdam study. Int J Obes Relat Metab Disord. 2001;25(11):1730–5. https://doi.org/10.1038/sj.ijo.0801787.

    Article  CAS  PubMed  Google Scholar 

  38. Romero-Corral A, Lopez-Jimenez F, Sierra-Johnson J, Somers VK. Differentiating between body fat and lean mass-how should we measure obesity? Nat Clin Pract Endocrinol Metab. 2008;4(6):322–3. https://doi.org/10.1038/ncpendmet0809.

    Article  PubMed  Google Scholar 

  39. Okorodudu DO, Jumean MF, Montori VM, Romero-Corral A, Somers VK, Erwin PJ, et al. Diagnostic performance of body mass index to identify obesity as defined by body adiposity: a systematic review and meta-analysis. Int J Obes. 2010;34(5):791–9. https://doi.org/10.1038/ijo.2010.5.

    Article  CAS  Google Scholar 

  40. Pischon T. Commentary: use of the body mass index to assess the risk of health outcomes: time to say goodbye? Int J Epidemiol. 2010:dyp388.

  41. Gallagher D, Visser M, Sepulveda D, Pierson RN, Harris T, Heymsfield SB. How useful is body mass index for comparison of body fatness across age, sex, and ethnic groups? Am J Epidemiol. 1996;143(3):228–39.

    Article  CAS  PubMed  Google Scholar 

  42. Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer. 2004;4(8):579–91.

    Article  CAS  PubMed  Google Scholar 

  43. Renehan AG, Zwahlen M, Egger M. Adiposity and cancer risk: new mechanistic insights from epidemiology. Nat Rev Cancer. 2015;15(8):484–98.

    Article  CAS  PubMed  Google Scholar 

  44. Wolfe RR. The underappreciated role of muscle in health and disease. Am J Clin Nutr. 2006;84(3):475–82.

    Article  CAS  PubMed  Google Scholar 

  45. Ruiz JR, Sui X, Lobelo F, Morrow JR, Jackson AW, Sjöström M, et al. Association between muscular strength and mortality in men: prospective cohort study. Bmj. 2008;337:a439.

    Article  PubMed  Google Scholar 

  46. Tsai S. Importance of lean body mass in the oncologic patient. Nutr Clin Pract. 2012;27(5):593–8.

    Article  PubMed  Google Scholar 

  47. Lee DH, Keum N, Hu FB, Orav EJ, Rimm EB, Willett WC, et al. Predicted lean body mass, fat mass, and all cause and cause specific mortality in men: prospective US cohort study. Bmj. 2018;362:k2575.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Lee DH, Giovannucci EL. Body composition and mortality in the general population: a review of epidemiologic studies. Exp Biol Med 2018;243(17-18):1275-85.

  49. • Brown JC, Cespedes Feliciano EM, Caan BJ. The evolution of body composition in oncology-epidemiology, clinical trials, and the future of patient care: facts and numbers. J Cachexia Sarcopenia Muscle. 2018;9(7):1200–8. https://doi.org/10.1002/jcsm.12379 This paper provides important perspectives of using body composition for cancer patient care.

    Article  PubMed  Google Scholar 

  50. • Cespedes Feliciano EM, Kroenke CH, Caan BJ. The obesity paradox in cancer: how important is muscle? Annual review of nutrition. 2018;38:357–379. A comprehensive review on the role of muscle in explaining the obesity paradox in cancer.

  51. •• Caan BJ, Feliciano EMC, Prado CM, Alexeeff S, Kroenke CH, Bradshaw P et al. Association of muscle and adiposity measured by computed tomography with survival in patients with nonmetastatic breast cancer. JAMA Oncol. 2018;4(6):798-804. This large study shows promising evidence that muscle and adiposity may provide significant prognositic information for breast cancer patients.

  52. •• Caan BJ, Meyerhardt JA, Kroenke CH, Alexeeff S, Xiao J, Weltzien E, et al. Explaining the obesity paradox: the association between body composition and colorectal cancer survival (C-SCANS Study). Cancer Epidemiol Biomarkers Prev. 2017;26(7):1008–15 This large study shows promising evidence that muscle and adiposity may provide significant prognostic information for colorectal cancer patients.

  53. Sealy MJ, Dechaphunkul T, van der Schans CP, Krijnen WP, Roodenburg JLN, Walker J et al. Low muscle mass is associated with early termination of chemotherapy related to toxicity in patients with head and neck cancer. Clinical Nutrition. https://doi.org/10.1016/j.clnu.2019.02.029.

  54. Kamarajah, SKA-Ohoo, Bundred J, Tan BHL. Body composition assessment and sarcopenia in patients with gastric cancer: a systematic review and meta-analysis.Gastric Cancer. 2019;22(1):10-22.

  55. • Shachar SS, Williams GR, Muss HB, Nishijima TF. Prognostic value of sarcopenia in adults with solid tumours: a meta-analysis and systematic review. Eur J Cancer. 2016;57:58–67 This meta-analysis of 38 studies provides important evidence that low muscle predicts poor clinical outcomes in cancer patients.

    Article  PubMed  Google Scholar 

  56. Mintziras I, Miligkos M, Wachter S, Manoharan J, Maurer E, Bartsch DK. Sarcopenia and sarcopenic obesity are significantly associated with poorer overall survival in patients with pancreatic cancer: systematic review and meta-analysis. Int J Surg. 2018;59:19-26.

  57. Hakimi AA, Furberg H, Zabor EC, Jacobsen A, Schultz N, Ciriello G, et al. An epidemiologic and genomic investigation into the obesity paradox in renal cell carcinoma. J Natl Cancer Inst. 2013;105(24):1862–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Crosbie EJ, Roberts C, Qian W, Swart AM, Kitchener HC, Renehan AG. Body mass index does not influence post-treatment survival in early stage endometrial cancer: results from the MRC ASTEC trial. Eur J Cancer. 2012;48(6):853–64.

    Article  PubMed  Google Scholar 

  59. Nagle C, Dixon S, Jensen A, Kjaer S, Modugno F, Fereday S, et al. Obesity and survival among women with ovarian cancer: results from the Ovarian Cancer Association Consortium. Br J Cancer. 2015;113(5):817–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of US adults. N Engl J Med. 2003;348(17):1625–38.

    Article  PubMed  Google Scholar 

  61. Ebadi M, Martin L, Ghosh S, Field CJ, Lehner R, Baracos VE, et al. Subcutaneous adiposity is an independent predictor of mortality in cancer patients. Br J Cancer. 2017;117(1):148–55.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Xiao J, Mazurak V, Olobatuyi T, Caan B, Prado C. Visceral adiposity and cancer survival: a review of imaging studies. Eur J Cancer Care. 2018;27(2):e12611.

    Article  CAS  Google Scholar 

  63. Pedersen BK, Febbraio MA. Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol. 2012;8(8):457–65.

    Article  CAS  PubMed  Google Scholar 

  64. Carneiro IP, Mazurak VC, Prado CM. Clinical implications of sarcopenic obesity in cancer. Curr Oncol Rep. 2016;18(10):62.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Nutrition, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA

    Dong Hoon Lee & Edward L. Giovannucci

  2. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Edward L. Giovannucci

  3. Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Edward L. Giovannucci

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Lee, D.H., Giovannucci, E.L. The Obesity Paradox in Cancer: Epidemiologic Insights and Perspectives. Curr Nutr Rep 8, 175–181 (2019). https://doi.org/10.1007/s13668-019-00280-6

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