Obesity and Cancer

Abstract

Epidemiological studies have suggested that obesity is associated with increased risk of several cancer types including colon, esophagus, breast (in postmenopausal women), endometrium, kidney, liver, gallbladder and pancreas. Suggested mechanisms include increased intake of potentially carcinogenic food ingredients along with excessive amount of calories, loss of cancer protective effects due to reduced physical activity, carcinogenic factors released from increased adipose tissue mass and “secondary” associations via “precursor” condition such as gallstones. The increased cancer risk in patients with obesity is a neglected topic which deserves more scientific attention. Because of its extreme chronicity and co-association with numerous other conditions true causality and underlying mechanisms are difficult to study. Nevertheless, a large body of literature is already available which provides concepts for future research.

cancer - estrogens - obesity - adipocytokines - leptin - insulin

References

• 1 Ogdan C. Advanced Data from Vital Health Statistics CDC.  2004; 
• 2 Olshansky SJ, Passaro DJ, Hershow RC. et al . A potential decline in life expectancy in the United States in the 21^st century.  N Engl J Med. 2005;  352 1138-1145
• 3 Vainio H, Bianchini F. Weight control and physical activity. International Agency for Cancer handbook of cancer prevention, Lyon: IARC. 2002;  6
• 4 Renehan AG, Tyson M, Egger M. et al . Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies.  Lancet. 2008;  371 569-578
• 5 Mokdad AH, Marks JS, Stroup DF. et al . Actual causes of death in the United States, 2000.  JAMA. 2004;  291 1238-1245
• 6 Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms.  Nat Rev Cancer. 2004;  4 579-591
• 7 Hursting SD, Lashinger LM, Wheatley KW. et al . Reducing the weight of cancer: mechanistic targets for breaking the obesity-carcinogenesis link.  Best Pract Res Clin Endocrinol Metab. 2008;  22 659-669
• 8 Jayachandran J, Banez LL, Aronson WJ. et al . Obesity as a predictor of adverse outcome across black and white race: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) Database.  Cancer. 2009; 
• 9 Bianchini F, Kaaks R, Vainio H. Overweight, obesity, and cancer risk.  Lancet Oncol. 2002;  3 565-574
• 10 Calle EE, Rodriguez C, Walker-Thurmond K. et al . Overweight, obesity, and mortality from cancer in a prospectively studied cohort of US adults.  N Engl J Med. 2003;  348 1625-1638
• 11 Galanis DJ, Kolonel LN, Lee J. et al . Anthropometric predictors of breast cancer incidence and survival in a multi-ethnic cohort of female residents of Hawaii, United States.  Cancer Causes Control. 1998;  9 217-224
• 12 Trentham-Dietz A, Newcomb PA, Egan KM. et al . Weight change and risk of postmenopausal breast cancer (United States).  Cancer Causes Control. 2000;  11 533-542
• 13 Kaaks R, Lukanova A, Kurzer MS. Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review.  Cancer Epidemiol Biomarkers Prev. 2002;  11 1531-1543
• 14 Hu J, Mao Y, White K. Overweight and obesity in adults and risk of renal cell carcinoma in Canada.  Soz Praventivmed. 2003;  48 178-185
• 15 Bergstrom A, Pisani P, Tenet V. et al . Overweight as an avoidable cause of cancer in Europe.  Int J Cancer. 2001;  91 421-430
• 16 Wild CP, Hardie LJ. Reflux, Barrett's oesophagus and adenocarcinoma: burning questions.  Nat Rev Cancer. 2003;  3 676-684
• 17 Lagergren J. Increased incidence of adenocarcinoma of the esophagus and cardia. Reflux and obesity are strong and independent risk factors according to the SECC study.  Lakartidningen. 2000;  97 1950-1953
• 18 Nilsson M, Johnsen R, Ye W. et al . Obesity and estrogen as risk factors for gastroesophageal reflux symptoms.  JAMA. 2003;  290 66-72
• 19 Gapstur SM, Gann PH, Lowe W. et al . Abnormal glucose metabolism and pancreatic cancer mortality.  JAMA. 2000;  283 2552-2558
• 20 Silverman DT, Swanson CA, Gridley G. et al . Dietary and nutritional factors and pancreatic cancer: a case-control study based on direct interviews.  J Natl Cancer Inst. 1998;  90 1710-1719
• 21 Wolk A, Gridley G, Svensson M. et al . A prospective study of obesity and cancer risk (Sweden).  Cancer Causes Control. 2001;  12 13-21
• 22 Strom BL, Soloway RD, Rios-Dalenz JL. et al . Risk factors for gallbladder cancer. An international collaborative case-control study.  Cancer. 1995;  76 1747-1756
• 23 Pan SY, DesMeules M. Energy intake, physical activity, energy balance, and cancer: epidemiologic evidence.  Methods Mol Biol. 2009;  472 191-215
• 24 Key TJ, Allen NE, Spencer EA. et al . The effect of diet on risk of cancer.  Lancet. 2002;  360 861-868
• 25 Thompson HJ. Ovesity as a cancer risk factor: potential mechanisms. Nutrition and Cancer Previntion, Taylor & Francis, Boca Raton, FL pp 2006: 565-57
• 26 Yakar S, Leroith D, Brodt P. The role of the growth hormone/insulin-like growth factor axis in tumor growth and progression: Lessons from animal models.  Cytokine Growth Factor Rev. 2005;  16 407-420
• 27 Shaw RJ, Cantley LC. Ras, PI(3)K and mTOR signalling controls tumour cell growth.  Nature. 2006;  441 424-430
• 28 Lukanova A, Zeleniuch-Jacquotte A, Lundin E. et al . Prediagnostic levels of C-peptide, IGF-I, IGFBP-1, -2 and -3 and risk of endometrial cancer.  Int J Cancer. 2004;  108 262-268
• 29 Abe R, Yamagishi S. AGE-RAGE system and carcinogenesis.  Curr Pharm Des. 2008;  14 940-945
• 30 Trayhurn P, Wood IS. Adipokines: inflammation and the pleiotropic role of white adipose tissue.  Br J Nutr. 2004;  92 347-355
• 31 Feagins LA, Souza RF, Spechler SJ. Carcinogenesis in IBD: potential targets for the prevention of colorectal cancer.  Nat Rev Gastroenterol Hepatol. 2009;  6 297-305
• 32 Stattin P, Lukanova A, Biessy C. et al . Obesity and colon cancer: does leptin provide a link?.  Int J Cancer. 2004;  109 149-152
• 33 Fenton JI, Hord NG, Lavigne JA. et al . Leptin, insulin-like growth factor-1, and insulin-like growth factor-2 are mitogens in ApcMin/+ but not Apc+/+ colonic epithelial cell lines.  Cancer Epidemiol Biomarkers Prev. 2005;  14 1646-1652
• 34 Rajala MW, Scherer PE. Minireview: The adipocyte--at the crossroads of energy homeostasis, inflammation, and atherosclerosis.  Endocrinology. 2003;  144 3765-3773
• 35 Gonzalez RR, Cherfils S, Escobar M. et al . Leptin signaling promotes the growth of mammary tumors and increases the expression of vascular endothelial growth factor (VEGF) and its receptor type two (VEGF-R2).  J Biol Chem. 2006;  281 26320-26328

Correspondence