The obesity paradox in cancer: clinical insights and perspectives

  • Ilaria Trestini
  • Luisa Carbognin
  • Clelia Bonaiuto
  • Giampaolo Tortora
  • Emilio BriaEmail author
Original Article
Part of the following topical collections:
  1. Obesity Paradox


A series of evidence demonstrated that obesity represents an established risk factor for an increase in the incidence of multiple cancer types and for poor cancer survival. Nevertheless, recent studies suggested that, in a series of cancers, patients with a normal body mass index (BMI) have worse outcomes than obese patients. This phenomenon, named ‘obesity paradox’ or ‘reverse epidemiology’ in cancer, is not well understood and presents controversial aspects. Therefore, this review aims to explore the available studies concerning the relationship between obesity and cancer incidence or survival and to highlight the hypothetical explanations and the methodological framework. In this regard, we underline the limits of BMI as a potential marker of adiposity and the relevance to assessing body composition, beyond the body size. Further studies are needed to define the impact of obesity in cancer patients, to tailor weight management after cancer diagnosis and to hopefully improve overall clinical outcome.


Obesity Cancer Obesity paradox Body mass index Body composition Sarcopenia 



The authors are supported by a grant of the Lega Italiana contro i Tumori (LILT-Bando di ricerca sanitaria 2016–5 × 1000 anno 2014).

Compliance with ethical standards

Conflict of interest

I.T., L.C. C.B., and G.T. declare that they have no conflict of interest. E.B. received honoraria or speakers’ fee from MSD, Astra-Zeneca, Celgene, Pfizer, Helsinn, Eli-Lilly, BMS, Novartis, and Roche, and he received research support from A.I.R.C. (Associazione Italiana Ricerca sul Cancro), I.A.S.L.C. (International Association for the Study of Lung Cancer), L.I.L.T. (Lega Italiana per la Lotta contro i Tumori), Fondazione Cariverona, Astra-Zeneca, Roche, and Open Innovation.

Ethical approval

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

Informed consent

For this type of study the informed consent was not required.


  1. 1.
    Flegal KM, Kruszon-Moran D, Carroll MD, Fryar CD, Ogden CL (2016) Trends in obesity among adults in the United States, 2005 to 2014. JAMA 315(21):2284–2291. CrossRefPubMedGoogle Scholar
  2. 2.
    Collaboration NCDRF. (2017) Worldwide trends in body mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults. Lancet 390(10113):2627–2642. CrossRefGoogle Scholar
  3. 3.
    Maffetone PB, Rivera-Dominguez I, Laursen PB (2017) Overfat adults and children in developed countries: the public health importance of identifying excess body fat. Front Public Health 5:190. CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Heymsfield SB, Wadden TA (2017) Mechanisms, pathophysiology, and management of obesity. N Engl J Med 376(3):254–266. CrossRefPubMedGoogle Scholar
  5. 5.
    Pollak M (2008) Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer 8(12):915–928. CrossRefPubMedGoogle Scholar
  6. 6.
    Leslie NR (2006) The redox regulation of PI 3-kinase-dependent signaling. Antioxid Redox Signal 8(9–10):1765–1774. CrossRefPubMedGoogle Scholar
  7. 7.
    Lohmann AE, Goodwin PJ, Chlebowski RT, Pan K, Stambolic V, Dowling RJ (2016) Association of obesity-related metabolic disruptions with cancer risk and outcome. J Clin Oncol 34(35):4249–4255. CrossRefPubMedGoogle Scholar
  8. 8.
    Pearson-Stuttard J, Zhou B, Kontis V, Bentham J, Gunter MJ, Ezzati M (2017) Worldwide burden of cancer attributable to diabetes and high body mass index: a comparative risk assessment. Lancet Diabetes Endocrinol. CrossRefPubMedGoogle Scholar
  9. 9.
    Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K, International Agency for Research on Cancer Handbook Working G (2016) Body fatness and cancer–viewpoint of the IARC working group. N Engl J Med 375 (8):794–798. CrossRefPubMedGoogle Scholar
  10. 10.
    Suzuki R, Orsini N, Saji S, Key TJ, Wolk A (2009) Body weight and incidence of breast cancer defined by estrogen and progesterone receptor status—a meta-analysis. Int J Cancer 124(3):698–712. CrossRefPubMedGoogle Scholar
  11. 11.
    Crosbie EJ, Roberts C, Qian W, Swart AM, Kitchener HC, Renehan AG (2012) Body mass index does not influence post-treatment survival in early stage endometrial cancer: results from the MRC ASTEC trial. Eur J Cancer 48(6):853–864. CrossRefPubMedGoogle Scholar
  12. 12.
    Jiralerspong S, Goodwin PJ (2016) Obesity and breast cancer prognosis: evidence, challenges, and opportunities. J Clin Oncol 34(35):4203–4216. CrossRefPubMedGoogle Scholar
  13. 13.
    Shachar SS, Williams GR (2017) The obesity paradox in cancer-moving beyond BMI-response. Cancer Epidemiol Biomark Prev 26(6):981. CrossRefGoogle Scholar
  14. 14.
    Daniel CR, Shu X, Ye Y, Gu J, Raju GS, Kopetz S, Wu X (2016) Severe obesity prior to diagnosis limits survival in colorectal cancer patients evaluated at a large cancer centre. Br J Cancer 114(1):103–109. CrossRefPubMedGoogle Scholar
  15. 15.
    Schlesinger S, Siegert S, Koch M, Walter J, Heits N, Hinz S, Jacobs G, Hampe J, Schafmayer C, Nothlings U (2014) Postdiagnosis body mass index and risk of mortality in colorectal cancer survivors: a prospective study and meta-analysis. Cancer Causes Control 25(10):1407–1418. CrossRefPubMedGoogle Scholar
  16. 16.
    Parker AS, Lohse CM, Cheville JC, Thiel DD, Leibovich BC, Blute ML (2006) Greater body mass index is associated with better pathologic features and improved outcome among patients treated surgically for clear cell renal cell carcinoma. Urology 68(4):741–746. CrossRefPubMedGoogle Scholar
  17. 17.
    Brunner AM, Sadrzadeh H, Feng Y, Drapkin BJ, Ballen KK, Attar EC, Amrein PC, McAfee SL, Chen YB, Neuberg DS, Fathi AT (2013) Association between baseline body mass index and overall survival among patients over age 60 with acute myeloid leukemia. Am J Hematol 88(8):642–646. CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Zhang X, Liu Y, Shao H, Zheng X (2017) Obesity paradox in lung cancer prognosis: evolving biological insights and clinical implications. J Thorac Oncol 12(10):1478–1488. CrossRefPubMedGoogle Scholar
  19. 19.
    Banack HR, Kaufman JS (2014) The obesity paradox: understanding the effect of obesity on mortality among individuals with cardiovascular disease. Prev Med 62:96–102. CrossRefPubMedGoogle Scholar
  20. 20.
    Kalantar-Zadeh K, Horwich TB, Oreopoulos A, Kovesdy CP, Younessi H, Anker SD, Morley JE (2007) Risk factor paradox in wasting diseases. Curr Opin Clin Nutr Metab Care 10(4):433–442. CrossRefPubMedGoogle Scholar
  21. 21.
    Amundson DE, Djurkovic S, Matwiyoff GN (2010) The obesity paradox. Crit Care Clin 26(4):583–596. CrossRefPubMedGoogle Scholar
  22. 22.
    Kalantar-Zadeh K, Abbott KC, Salahudeen AK, Kilpatrick RD, Horwich TB (2005) Survival advantages of obesity in dialysis patients. Am J Clin Nutr 81(3):543–554CrossRefGoogle Scholar
  23. 23.
    Bosello O, Donataccio MP, Cuzzolaro M (2016) Obesity or obesities? Controversies on the association between body mass index and premature mortality. Eat Weight Disord 21(2):165–174. CrossRefPubMedGoogle Scholar
  24. 24.
    Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ (2003) Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 348(17):1625–1638. CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Goodwin PJ, Chlebowski RT (2016) Obesity and cancer: insights for clinicians. J Clin Oncol 34(35):4197–4202. CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Key TJ, Pike MC (1988) The role of oestrogens and progestagens in the epidemiology and prevention of breast cancer. Eur J Cancer Clin Oncol 24(1):29–43CrossRefGoogle Scholar
  27. 27.
    Siiteri PK (1987) Adipose tissue as a source of hormones. Am J Clin Nutr 45(1 Suppl):277–282CrossRefGoogle Scholar
  28. 28.
    Rotondi M, Castagna MG, Cappelli C, Ciuoli C, Coperchini F, Chiofalo F, Maino F, Palmitesta P, Chiovato L, Pacini F (2016) Obesity does not modify the risk of differentiated thyroid cancer in a cytological series of thyroid nodules. Eur Thyroid J 5(2):125–131. CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Dignam JJ, Polite BN, Yothers G, Raich P, Colangelo L, O’Connell MJ, Wolmark N (2006) Body mass index and outcomes in patients who receive adjuvant chemotherapy for colon cancer. J Natl Cancer Inst 98(22):1647–1654. CrossRefPubMedGoogle Scholar
  30. 30.
    Efstathiou JA, Bae K, Shipley WU, Hanks GE, Pilepich MV, Sandler HM, Smith MR (2007) Obesity and mortality in men with locally advanced prostate cancer: analysis of RTOG 85 – 31. Cancer 110(12):2691–2699. CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Protani MM, Nagle CM, Webb PM (2012) Obesity and ovarian cancer survival: a systematic review and meta-analysis. Cancer Prev Res (Phila) 5(7):901–910. CrossRefGoogle Scholar
  32. 32.
    Fedele P, Orlando L, Schiavone P, Quaranta A, Lapolla AM, De Pasquale M, Ardizzone A, Bria E, Sperduti I, Calvani N, Marino A, Caliolo C, Mazzoni E, Cinieri S (2014) BMI variation increases recurrence risk in women with early-stage breast cancer. Futur Oncol 10(15):2459–2468. CrossRefGoogle Scholar
  33. 33.
    Stone E, Slatore CG (2017) The obesity paradox-what does it mean for lung cancer surgery? J Thorac Oncol 12(8):1174–1176. CrossRefPubMedGoogle Scholar
  34. 34.
    Choi Y, Park B, Jeong BC, Seo SI, Jeon SS, Choi HY, Adami HO, Lee JE, Lee HM (2013) Body mass index and survival in patients with renal cell carcinoma: a clinical-based cohort and meta-analysis. Int J Cancer 132(3):625–634. CrossRefPubMedGoogle Scholar
  35. 35.
    Donin NM, Pantuck A, Klopfer P, Bevan P, Fall B, Said J, Belldegrun AS, Chamie K (2016) Body mass index and survival in a prospective randomized trial of localized high-risk renal cell carcinoma. Cancer Epidemiol Biomark Prev 25 (9):1326–1332. CrossRefGoogle Scholar
  36. 36.
    Bertrand LA, Thomas LJ, Li P, Buchta CM, Boi SK, Orlandella RM, Brown JA, Nepple KG, Norian LA (2017) Obesity as defined by waist circumference but not body mass index is associated with higher renal mass complexity. Urol Oncol 35(11):661. (e661–661 e666)CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Lam VK, Bentzen SM, Mohindra P, Nichols EM, Bhooshan N, Vyfhuis M, Scilla KA, Feigenberg SJ, Edelman MJ, Feliciano JL (2017) Obesity is associated with long-term improved survival in definitively treated locally advanced non-small cell lung cancer (NSCLC). Lung Cancer 104:52–57. CrossRefPubMedGoogle Scholar
  38. 38.
    Sepesi B, Gold KA, Correa AM, Heymach JV, Vaporciyan AA, Roszik J, Dmitrovsky E, Liu X (2017) The influence of body mass index on overall survival following surgical resection of non-small cell lung cancer. J Thorac Oncol 12(8):1280–1287. CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Dahlberg SE, Schiller JH, Bonomi PB, Sandler AB, Brahmer JR, Ramalingam SS, Johnson DH (2013) Body mass index and its association with clinical outcomes for advanced non-small-cell lung cancer patients enrolled on Eastern Cooperative Oncology Group clinical trials. J Thorac Oncol 8(9):1121–1127. CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Li S, Wang Z, Huang J, Fan J, Du H, Liu L, Che G (2017) 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 51(5):817–828. CrossRefPubMedGoogle Scholar
  41. 41.
    Attaran S, McShane J, Whittle I, Poullis M, Shackcloth M (2012) A propensity-matched comparison of survival after lung resection in patients with a high versus low body mass index. Eur J Cardiothorac Surg 42(4):653–658. CrossRefPubMedGoogle Scholar
  42. 42.
    Tsang NM, Pai PC, Chuang CC, Chuang WC, Tseng CK, Chang KP, Yen TC, Lin JD, Chang JT (2016) Overweight and obesity predict better overall survival rates in cancer patients with distant metastases. Cancer Med 5(4):665–675. CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Albiges L, Hakimi AA, Xie W, McKay RR, Simantov R, Lin X, Lee JL, Rini BI, Srinivas S, Bjarnason GA, Ernst S, Wood LA, Vaishamayan UN, Rha SY, Agarwal N, Yuasa T, Pal SK, Bamias A, Zabor EC, Skanderup AJ, Furberg H, Fay AP, de Velasco G, Preston MA, Wilson KM, Cho E, McDermott DF, Signoretti S, Heng DY, Choueiri TK (2016) Body mass index and metastatic renal cell carcinoma: clinical and biological correlations. J Clin Oncol. CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Martel S, Poletto E, Ferreira AR, Lambertini M, Sottotetti F, Bertolini I, Montemurro F, Bernardo A, Risi E, Zanardi E, Ziliani S, Mura S, Dellepiane C, Del Mastro L, Minisini AM, Puglisi F (2017) Impact of body mass index on the clinical outcomes of patients with HER2-positive metastatic breast cancer. Breast 37:142–147. CrossRefPubMedGoogle Scholar
  45. 45.
    Muller MJ, Bosy-Westphal A, Krawczak M (2010) Genetic studies of common types of obesity: a critique of the current use of phenotypes. Obes Rev 11(8):612–618. CrossRefPubMedGoogle Scholar
  46. 46.
    Davies M (2005) Nutritional screening and assessment in cancer-associated malnutrition. Eur J Oncol Nurs 9(Suppl 2):S64-73. CrossRefPubMedGoogle Scholar
  47. 47.
    Noori N, Kovesdy CP, Dukkipati R, Kim Y, Duong U, Bross R, Oreopoulos A, Luna A, Benner D, Kopple JD, Kalantar-Zadeh K (2010) Survival predictability of lean and fat mass in men and women undergoing maintenance hemodialysis. Am J Clin Nutr 92(5):1060–1070. CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Martin L, Birdsell L, Macdonald N, Reiman T, Clandinin MT, McCargar LJ, Murphy R, Ghosh S, Sawyer MB, Baracos VE (2013) Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index. J Clin Oncol 31(12):1539–1547. CrossRefPubMedGoogle Scholar
  49. 49.
    Wu S, Liu J, Wang X, Li M, Gan Y, Tang Y (2014) Association of obesity and overweight with overall survival in colorectal cancer patients: a meta-analysis of 29 studies. Cancer Causes Control 25(11):1489–1502. CrossRefPubMedGoogle Scholar
  50. 50.
    Walter V, Jansen L, Hoffmeister M, Ulrich A, Roth W, Blaker H, Chang-Claude J, Brenner H (2016) Prognostic relevance of prediagnostic weight loss and overweight at diagnosis in patients with colorectal cancer. Am J Clin Nutr 104(4):1110–1120. CrossRefPubMedGoogle Scholar
  51. 51.
    Gonzalez MC, Pastore CA, Orlandi SP, Heymsfield SB (2014) Obesity paradox in cancer: new insights provided by body composition. Am J Clin Nutr 99(5):999–1005. CrossRefPubMedGoogle Scholar
  52. 52.
    Prado CM, Lieffers JR, McCargar LJ, Reiman T, Sawyer MB, Martin L, Baracos VE (2008) Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol 9(7):629–635. CrossRefPubMedGoogle Scholar
  53. 53.
    Ebadi M, Martin L, Ghosh S, Field CJ, Lehner R, Baracos VE, Mazurak VC (2017) Subcutaneous adiposity is an independent predictor of mortality in cancer patients. Br J Cancer 117(1):148–155. CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Fontana L, Eagon JC, Trujillo ME, Scherer PE, Klein S (2007) Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes 56(4):1010–1013. CrossRefPubMedGoogle Scholar
  55. 55.
    Ibrahim MM (2010) Subcutaneous and visceral adipose tissue: structural and functional differences. Obes Rev 11(1):11–18. CrossRefPubMedGoogle Scholar
  56. 56.
    Ogino S, Shima K, Baba Y, Nosho K, Irahara N, Kure S, Chen L, Toyoda S, Kirkner GJ, Wang YL, Giovannucci EL, Fuchs CS (2009) Colorectal cancer expression of peroxisome proliferator-activated receptor gamma (PPARG, PPARgamma) is associated with good prognosis. Gastroenterology 136(4):1242–1250. CrossRefPubMedGoogle Scholar
  57. 57.
    Okamura A, Watanabe M, Yamashita K, Yuda M, Hayami M, Imamura Y, Mine S (2017) Implication of visceral obesity in patients with esophageal squamous cell carcinoma. Langenbeck’s Arch Surg. CrossRefGoogle Scholar
  58. 58.
    Wang SL, Ma LL, Chen XY, Zhou DL, Li B, Huang DD, Yu Z, Shen X, Zhuang CL (2017) Impact of visceral fat on surgical complications and long-term survival of patients with gastric cancer after radical gastrectomy. Eur J Clin Nutr. CrossRefPubMedGoogle Scholar
  59. 59.
    Caan BJ, Meyerhardt JA, Kroenke CH, Alexeeff S, Xiao J, Weltzien E, Feliciano EC, Castillo AL, Quesenberry CP, Kwan ML, Prado CM (2017) Explaining the obesity paradox: the association between body composition and colorectal cancer survival (C-SCANS study). Cancer Epidemiol Biomark Prev 26(7):1008–1015CrossRefGoogle Scholar
  60. 60.
    Thoresen L, Frykholm G, Lydersen S, Ulveland H, Baracos V, Prado CM, Birdsell L, Falkmer U (2013) Nutritional status, cachexia and survival in patients with advanced colorectal carcinoma. Different assessment criteria for nutritional status provide unequal results. Clin Nutr 32(1):65–72. CrossRefPubMedGoogle Scholar
  61. 61.
    Donohoe CL, Ryan AM, Reynolds JV (2011) Cancer cachexia: mechanisms and clinical implications. Gastroenterol Res Pract 2011:601434. CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Horiguchi A, Asano T, Asano T, Ito K, Sumitomo M, Hayakawa M (2008) Fatty acid synthase over expression is an indicator of tumor aggressiveness and poor prognosis in renal cell carcinoma. J Urol 180(3):1137–1140. CrossRefPubMedGoogle Scholar
  63. 63.
    Hakimi AA, Furberg H, Zabor EC, Jacobsen A, Schultz N, Ciriello G, Mikklineni N, Fiegoli B, Kim PH, Voss MH, Shen H, Laird PW, Sander C, Reuter VE, Motzer RJ, Hsieh JJ, Russo P (2013) An epidemiologic and genomic investigation into the obesity paradox in renal cell carcinoma. J Natl Cancer Inst 105(24):1862–1870. CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Ito R, Narita S, Huang M, Nara T, Numakura K, Takayama K, Tsuruta H, Maeno A, Saito M, Inoue T, Tsuchiya N, Satoh S, Habuchi T (2017) The impact of obesity and adiponectin signaling in patients with renal cell carcinoma: a potential mechanism for the “obesity paradox”. PLoS One 12(2):e0171615. CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Prado CM, Gonzalez MC, Heymsfield SB (2015) Body composition phenotypes and obesity paradox. Curr Opin Clin Nutr Metab Care 18(6):535–551. CrossRefPubMedGoogle Scholar
  66. 66.
    Lancefield T, Clark DJ, Andrianopoulos N, Brennan AL, Reid CM, Johns J, Freeman M, Charter K, Duffy SJ, Ajani AE, Proietto J, Farouque O, Registry MIG (2010) Is there an obesity paradox after percutaneous coronary intervention in the contemporary era? An analysis from a multicenter Australian registry. JACC Cardiovasc Interv 3(6):660–668. CrossRefPubMedGoogle Scholar
  67. 67.
    Navarro WH, Agovi MA, Logan BR, Ballen K, Bolwell BJ, Frangoul H, Gupta V, Hahn T, Ho VT, Juckett M, Lazarus HM, Litzow MR, Liesveld JL, Moreb JS, Marks DI, McCarthy PL, Pasquini MC, Rizzo JD (2010) Obesity does not preclude safe and effective myeloablative hematopoietic cell transplantation (HCT) for acute myelogenous leukemia (AML) in adults. Biol Blood Marrow Transplant 16(10):1442–1450. CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Calabia J, Arcos E, Carrero JJ, Comas J, Valles M (2015) Does the obesity survival paradox of dialysis patients differ with age? Blood Purif 39(1–3):193–199. CrossRefPubMedGoogle Scholar
  69. 69.
    Braun N, Gomes F, Schutz P (2015) “The obesity paradox” in disease—is the protective effect of obesity true? Swiss Med Wkly 145:w14265. CrossRefPubMedGoogle Scholar
  70. 70.
    Henley SJ, Flanders WD, Manatunga A, Thun MJ (2002) Leanness and lung cancer risk: fact or artifact? Epidemiology 13(3):268–276CrossRefGoogle Scholar
  71. 71.
    Peeters A (2017) Journals should no longer accept ‘obesity paradox’ articles. Int J Obes. CrossRefGoogle Scholar
  72. 72.
    Banack HR, Stokes A (2017) The ‘obesity paradox’ may not be a paradox at all. Int J Obes 41(8):1162–1163. CrossRefGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.U.O.C. OncologyUniversity of Verona, Azienda Ospedaliera Universitaria IntegrataVeronaItaly

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