Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00050348.xml
Download PDF
CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2020; 41(03): 328-334
DOI: 10.4103/ijmpo.ijmpo_117_20
DOI: 10.4103/ijmpo.ijmpo_117_20
Review Article
Obesity-related Cancers: The Coming Epidemic
Financial support and sponsorship Nil.
Abstract
The world is in the grip of an obesity pandemic, with tripling of obesity rates since 1975; it is predicted that one-third of people on Earth will be obese by 2025. The health consequences of obesity are primarily thought to be related to cardiometabolic disorders such as diabetes and cardiovascular diseases. It is less well appreciated that obesity has been related to at least 13 different cancers and in future, (with increasing control over tobacco misuse and infections), obesity will be the main cause of cancers. While this is an area of active research, there are large gaps in the definition of what is an obesity related cancer (JRC) and more importantly, what are the underlying mechanisms. To an extent, this is due to the controversy on what constitutes “unhealthy obesity” which is further related to the causes of obesity. This narrative review examines the causes and measurement of obesity, the types of obesity-related cancers and possible mechanisms. The information has wide implications ranging from prevention, screening, prognosis and therapeutic strategies. Obesity related cancers should be an area of high-priority research. Oncologists can contribute by spreading awareness and instituting management measures for individual patients in their care.
Keywords
Carbohydrate-insulin model - gut microbiome - hyperinsulinemia - obesity - obesity-related cancers - sarcopenic obesityPublication History
Received: 31 March 2020
Accepted: 26 May 2020
Article published online:
28 June 2021
© 2020. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
-
References
- 1 Arnold M, Leitzmann M, Freisling H, Bray F, Romieu I, Renehan A. et al. Obesity and cancer: An update of the global impact. Cancer Epidemiol 2016; 41: 8-15
- 2 Mariosa D, Carreras-Torres R, Martin RM, Johansson M, Brennan P. Commentary: What can Mendelian randomization tell us about causes of cancer?. Int J Epidemiol 2019; 48: 816-21
- 3 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. Br J Cancer 2018; 118: 1130-41
- 4 Hong YR, Huo J, Desai R, Cardel M, Deshmukh AA. Deshmukh AA. Excess costs and economic burden of obesity-related cancers in the United States. Value Health 2019; 22: 1378-86
- 5 Koroukian SM, Dong W, Berger NA. Changes in age distribution of obesity-associated cancers. JAMA Netw Open 2019; 2: e199261
- 6 Bjørge T, Häggström C, Ghaderi S, Nagel G, Manjer J, Tretli S. et al. BMI and weight changes and risk of obesity-related cancers: A pooled European cohort study. Int J Epidemiol 2019; 48: 1872-85
- 7 Stigler FL, Lustig RH, Ma JI. Mechanisms, pathophysiology, and management of obesity. N Engl J Med 2017; 376: 1491
- 8 Ludwig DS, Ebbeling CB. The carbohydrate-insulin model of obesity: Beyond “calories in, calories out”. JAMA Intern Med 2018; 178: 1098-103
- 9 Moussa O, Arhi C, Ziprin P, Darzi A, Khan O, Purkayastha S. Fate of the metabolically healthy obese-is this term a misnomer? A study from the clinical practice research datalink. Int J Obes (Lond) 2019; 43: 1093-101
- 10 Korduner J, Bachus E, Jujic A, Magnusson M, Nilsson PM. Metabolically healthy obesity (MHO) in the Malmö diet cancer study Epidemiology and prospective risks. Obes Res Clin Pract 2019; 13: 548-54
- 11 Iyengar NM, Arthur R, Manson JE, Chlebowski RT, Kroenke CH, Peterson L. et al. Association of body fat and risk of breast cancer in postmenopausal women with normal body mass index: A secondary analysis of a randomized clinical trial and observational study. JAMA Oncol 2019; 5: 155-63
- 12 Zdrojewicz Z, Popowicz E, Szyca M, Michalik T, Śmieszniak B. TOFI phenotype-its effect on the occurrence of diabetes. Pediatr Endocrinol Diabetes Metab 2017; 23: 96-100
- 13 Shulman GI. Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. N Engl J Med 2014; 371: 1131-41
- 14 Ross R, Neeland IJ, Yamashita S, Shai I, Seidell J, Magni P. et al. Waist circumference as a vital sign in clinical practice: A Consensus Statement from the IAS and ICCR Working Group on Visceral Obesity. Nat Rev Endocrinol 2020; 16: 177-89
- 15 Woolcott OO, Woolcott RN. Defining cutoffs to diagnose obesity using the relative fat mass (RFM): Association with mortality in NHANES 1999-2014. Int J Obes (Lond) 2020; 44: 1301-10
- 16 Allen AM, Hicks SB, Mara KC, Larson JJ, Therneau TM. The risk of incident extrahepatic cancers is higher in non-alcoholic fatty liver disease than obesity-A longitudinal cohort study. J Hepatol 2019; 71: 1229-36
- 17 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. New England J Med 2016; 375: 794-8
- 18 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: e0177875
- 19 Genkinger JM, Wu K, Wang M, Albanes D, Black A, van den BrandtPA. et al Measures of body fatness and height in early and mid-to-late adulthood and prostate cancer: Risk and mortality in The pooling project of prospective studies of diet and cancer. Ann Oncol 2020; 31: 103-14
- 20 Santos AP, Santos AC, Castro C, Raposo L, Pereira SS, Torres I. et al. Visceral obesity and metabolic syndrome are associated with well-differentiated gastroenteropancreatic neuroendocrine tumors. Cancer s (Basel) 2018; 10: 293
- 21 Choi JB, Lee EJ, Han KD, Hong SH, Ha US. Estimating the impact of body mass index on bladder cancer risk: Stratification by smoking status. Sci Rep 2018; 8: 947
- 22 Cieslik M, Chinnaiyan AM. Global genomics project unravels cancer's complexity at unprecedented scale. Nature 2020; 578: 39-40
- 23 Wang D, Dubois RN. Associations between obesity and cancer: The role of fatty acid synthase. J Natl Cancer Inst 2012; 104: 343-5
- 24 Akbari ME, Gholamalizadeh M, Doaei S, Mirsafa F. FTO gene affects obesity and breast cancer through similar mechanisms: A new insight into the molecular therapeutic targets. Nutr Cancer 2018; 70: 30-6
- 25 Deng X, Su R, Stanford S, Chen J. Critical enzymatic functions of FTO in obesity and cancer. Front Endocrinol (Lausanne) 2018; 9: 369
- 26 Schünemann H, Hill S, Guyatt G, Akl EA, Ahmed F. The GRADE approach and Bradford Hill's criteria for causation. J Epidemiol Community Health 2011; 65: 392-5
- 27 Campbell PT. Obesity: A certain and avoidable cause of cancer. Lancet 2014; 384: 727-8
- 28 Smith LA, O'Flanagan CH, Bowers LW, Allott EH, Hursting SD. Translating mechanism-based strategies to break the obesity-cancer link: A narrative review. J Acad Nutr Diet 2018; 188: 652-67
- 29 Kompella P, Vasquez KM. Obesity and cancer: A mechanistic overview of metabolic changes in obesity that impact genetic instability. Mol Carcinog 2019; 58: 1531-50
- 30 Erion KA, Corkey BE. Hyperinsulinemia: A cause of obesity?. Curr Obes Rep 2017; 6: 178-86
- 31 Vigneri R, Goldfine ID, Frittitta L. Insulin, insulin receptors, and cancer. J Endocrinol Invest 2016; 39: 1365-76
- 32 Parekh N, Guffanti G, Lin Y, Ochs-Balcom HM, Makarem N, Hayes R. Insulin receptor variants and obesity-related cancers in the Framingham Heart Study. Cancer Causes Control 2015; 26: 1189-95
- 33 Tsujimoto T, Kajio H, Sugiyama T. Association between hyperinsulinemia and increased risk of cancer death in nonobese and obese people: A population-based observational study. Int J Cancer 2017; 141: 102-11
- 34 Turati F, Galeone C, Gandini S, Augustin LS, Jenkins DJ, Pelucchi C. et al. High glycemic index and glycemic load are associated with moderately increased cancer risk. Mol Nutr Food Res 2015; 59: 1384-94
- 35 Nyasani E, Munir I, Perez M, Payne K, Khan S. Linking obesity-induced leptin-signaling pathways to common endocrine-related cancers in women. Endocrine 2019; 63: 3-17
- 36 Yoon YS, Kwon AR, Lee YK, Oh SW. Circulating adipokines and risk of obesity related cancers: A systematic review and meta-analysis. Obes Res Clin Pract 2019; 13: 329-39
- 37 Inagaki-Ohara K. Gastric leptin and tumorigenesis: Beyond obesity. Int J Mol Sci 2019; 20: 2622
- 38 Hao J, Zhang Y, Yan X, Yan F, Sun Y, Zeng J. et al. Circulating adipose fatty acid binding protein is a new link underlying obesity-associated breast/mammary tumor development. Cell Metabe 2018; 28: 689-705
- 39 Starling S. Obesity-linked inflammation tied to glutamine levels. Nat Rev Endocrinol 2020; 16: 130-1
- 40 Quail DF, Dannenberg AJ. The obese adipose tissue microenvironment in cancer development and progression. Nat Rev Endocrinol 2019; 15: 139-54
- 41 Włodarczyk M, Nowicka G. Obesity, DNA damage, and development of obesity-related diseases. Int J Mol Sci 2019; 20: 2622
- 42 Valdes AM, Walter J, Segal E, Spector TD. Role of the gut microbiota in nutrition and health. BMJ 2018; 361: k2179
- 43 Cani PD, Jordan BF. Gut microbiota-mediated inflammation in obesity: A link with gastrointestinal cancer. Nat Rev Gastroenterol Hepatol 2018; 15: 671-82
- 44 Greathouse KL, White JR, Padgett RN, Perrotta BG, Jenkins GD, Chia N. et al. Gut microbiome meta-analysis reveals dysbiosis is independent of body mass index in predicting risk of obesity-associated CRC. BMJ Open Gastroenterol 2019; 6: e000247
- 45 Luo J, Hendryx M, Manson JE, Figueiredo JC, LeBlanc ES, Barrington W. et al. Intentional weight loss and obesity-related cancer risk. JNCI Cancer Spectrum 2019; 3: pkz054
- 46 Zhang K, Luo Y, Dai H, Deng Z. Effects of bariatric surgery on cancer risk: Evidence from meta-analysis. Obesity Surg 2020; 30: 1265-72
- 47 Taube M, Peltonen M, Sjoholm K, Anveden A, Andersson-Assarsson JC, Jacobson P. et al. Association of bariatric surgery with skin cancer incidence in adults with obesity: A nonrandomized controlled trial. JAMA Dermatol 2019; 156: 1-7
- 48 Iacobucci G. Treat obesity with the same effort used to reduce smoking, says lead psychologist. BMJ 2019; 366: l5713
- 49 Shu X, Wu L, Khankari NK, Shu XO, Wang TJ, Michailidou K. et al. Associations of obesity and circulating insulin and glucose with breast cancer risk: A Mendelian randomization analysis. Int J Epidemiol 2019; 48: 795-806
- 50 Del Pozo MD, Castelló A, Vidal C, Salas-Trejo D, Sánchez-Contador C, Pedraz-Pingarrón C. et al. Overeating, caloric restriction and mammographic density in Spanish women. DDM-Spain study. Maturitas 2018; 117: 57-63
- 51 Moke DJ, Hamilton AS, Chehab L, Deapen D, Freyer DR. Obesity and risk for second malignant neoplasms in childhood cancer survivors: A case-control study utilizing the california cancer registry. Cancer Epidemiol Biomarkers Prev ent 2019; 28: 1612-20
- 52 Heetun A, Cutress RI, Copson ER. Early breast cancer: Why does obesity affect prognosis?. Proc Nutr Soc 2018; 77: 369-81
- 53 Osman MA, Hennessy BTK. Obesity correlation with metastases development and response to first-line metastatic chemotherapy in breast cancer. Clin Med Insights Oncol 2015; 9: 105-12
- 54 Barua R, Templeton AJ, Seruga B, Ocana A, Amir E, Ethier JL. Hyperglycaemia and survival in solid tumours: A systematic review and meta-analysis. Clin Oncol (R Coll Radiol) 2018; 30: 215-24
- 55 Lennon H, Sperrin M, Badrick E, Renehan AG. The obesity paradox in cancer: A review. Curr Oncol Rep 2016; 18: 56
- 56 Renehan AG, Sperrin M. The obesity paradox and mortality after colorectal cancer: A causal conundrum. JAMA Oncol 2016; 2: 1127-9
- 57 Lee DH, Giovannucci EL. The obesity paradox in cancer: Epidemiologic insights and perspectives. Curr Nutr Rep 2019; 8: 175-81
- 58 Sperrin M, Candlish J, Badrick E, Renehan A, Buchan I. Collider bias is only a partial explanation for the obesity paradox. Epidemiology 2016; 27: 525-30
- 59 Ujvari B, Jacqueline C, Misse D, Amar V, Fitzpatrick JC, Jennings G. Obesity paradox in cancer: Is bigger really better?. Evolutionary Appl 2019; 12: 1092-5
- 60 Sanchez A, Furberg H, Kuo F, Vuong L, Ged Y, Patil S. et al. Transcriptomic signatures related to the obesity paradox in patients with clear cell renal cell carcinoma: A cohort study. Lancet Oncol 2020; 21: 283-93
- 61 Renehan AG, Harvie M, Cutress RI, Leitzmann M, Pischon T, Howell S. et al. How to manage the obese patient with cancer. J Clin Oncol 2016; 34: 4284-94
- 62 Lyman GH, Sparreboom A. Chemotherapy dosing in overweight and obese patients with cancer. Nat Rev Clin Oncol 2013; 10: 451-9
- 63 Lehuede C, Li X, Dauvillier S, Vaysse C, Franchet C, Clement E. et al. Adipocytes promote breast cancer resistance to chemotherapy, a process amplified by obesity: Role of the major vault protein (MVP). Breast Cancer Res 2019; 21: 7
- 64 Zhang Z, Scherer PE. Adipose tissue: The dysfunctional adipocyte A cancer cell's best friend. Nat Rev Endocrinol 2018; 14: 132-4
- 65 Kosalka P, Johnson C, Turek M, Sulpher J, Law A, Botros J, Sarin YK. et al. Effect of obesity, dyslipidemia, and diabetes on trastuzumab-related cardiotoxicity in breast cancer. Curr Oncol 2019; 26: e314-e321
- 66 Cespedes Feliciano EM, Chen WY, Lee V, Albers KB, Prado CM, Alexeeff S. et al. Body composition, adherence to anthracycline and taxane-based chemotherapy, and survival after nonmetastatic breast cancer. JAMA Oncol 2019; 6: 264-70
- 67 Lysaght J. The 'obesity paradox' in action with cancer immunotherapy. Nat Rev Endocrinol 2019; 15: 132-3
- 68 Menendez JA, Lupu R. Fatty acid synthase (FASN) as a therapeutic target in breast cancer. Expert Opin Ther Targets 2017; 21: 1001-16
- 69 McMurray F, Demetriades M, Aik W, Merkestein M, Kramer H, Andrew DS. et al. Pharmacological inhibition of FTO. PLoS One 2015; 10: e0121829
- 70 Prado CM, Lieffers JR, McCargar LJ, Reiman T, Sawyer MB, Martin L. et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: A population-based study. Lancet Oncol 2008; 9: 629-35
- 71 Yip C, Dinkel C, Mahajan A, Siddique M, Cook GJ, Goh V. Imaging body composition in cancer patients: Visceral obesity, sarcopenia and sarcopenic obesity may impact on clinical outcome. Insights Imaging 2015; 6: 489-97
- 72 Ligibel JA, Alfano CM, Courneya KS, Demark-Wahnefried W, Burger RA, Chlebowski RT. et al. American Society of Clinical Oncology position statement on obesity and cancer. J Clin Oncol 2014; 32: 3568-74
- 73 Renehan AG, Lloyd K, Renehan I. Awareness of the link between obesity and cancer in UK school curricula. Lancet 2019; 393: 1591-2
- 74 Venniyoor A. The most important questions in cancer research and clinical oncology-Question 2-5. Obesity-related cancers: More questions than answers. Chin J Cancer 2017; 36: 18
- 75 Misra A, Chowbey P, Makkar BM, Vikram NK, Wasir JS, Chadha D. et al. Consensus statement for diagnosis of obesity, abdominal obesity and the metabolic syndrome for Asian Indians and recommendations for physical activity, medical and surgical management. J Assoc Physicians India 2009; 57: 163-70