Obesity: impact on Colorectal Carcinoma

  • Maria Leonor Táboas Simões Faculdade de Medicina da Universidade do Porto
  • Laura E. Barbosa Faculdade de Medicina da Universidade do Porto

Abstract

Introduction: The increasing prevalence of obesity is a serious public health problem which is associated with an increased risk of many diseases that result in great morbidity and mortality. Some cancers seem to be among these, one of these being colorectal carcinoma (CRC). The aim of this study is to evaluate the impact of obesity as a risk factor for CRC and to discuss the mechanisms that may establish a link between this cancer and obesity. Methods: A research was conducted in PubMed database, limited to ten years, with the articles considered to be relevant being selected after reading the title and abstract. Results: There is a statistically significant positive association between CRC and obesity, with the risk being higher for males and for colon compared with the rectum, for most studies. In spite of body mass index (BMI) being the most widely used measure for obesity estimation in studies in the CRC area, it was found an increased risk of this neoplasm when using measurements of visceral obesity, such as waist circumference or waist-hip ratio, compared to BMI, reflecting the importance of body fat distribution in this association. The most inconsistent results were observed for the risk of rectal cancer in females. In what concerns the association comparing between proximal and distal colon and the effect of a weight change during adulthood in the risk of colon carcinoma, the evidence is still limited and discordant. Conclusions: Although the mechanisms that underlie the observed association between obesity and CRC are not yet fully understood, some hypothesis have been proposed, focusing primarily on metabolic and hormonal activity of visceral adiposity. This study highlights the importance of obesity as a risk factor for CRC, reinforcing the importance of the weight control and the avoidance of excess body fat accumulation. New research approaches may become more relevant in the future and may help to clarify some issues for which the evidence is still limited.

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Author Biographies

Maria Leonor Táboas Simões, Faculdade de Medicina da Universidade do Porto

Licenciada em Ciências Básicas da Saúde, Faculdade de Medicina da Universidade do Porto

Serviço de Cirurgia Geral

Laura E. Barbosa, Faculdade de Medicina da Universidade do Porto

Mestre, Faculdade de Medicina da Universidade do Porto

Serviço de Cirurgia Geral

References

1. WHO: Obesity and Overweight. 2011; Fact sheet N°311. Disponível em: http://www.who.int/mediacentre/factsheets/fs311/en.

2. Finucane MM, Stevens GA, Cowan MJ, et al.: National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet 2011;377 (9765)557-67.

3. WHO. Obesity: data and statistics: WHO Regional Office for Europe. Disponível em: http://www.euro.who.int/en/health-topics/noncommunicable-diseases/obesity

4. Flegal KM, Carroll MD, Kit BK, Ogden CL: Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010. JAMA 2012;307(5)491-7.

5. OECD. Obesity Update 2012. Disponível em: http://www.oecd.org/health/49716427.pdf

6. Fontaine KR, Redden DT, Wang C, Westfall AO, Allison DB: Years of life lost due to obesity. JAMA 2003;289(2)187 -93.

7. Rickles AS, Iannuzzi JC, Mironov O, et al.: Visceral obesity and colorectal cancer: are we missing the boat with BMI? J Gastrointest Surg.
2013;17(1)133-43

8. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M: Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 2008;371(9612)569-78

9. Wolin KY, Carson K, Colditz GA: Obesity and cancer. Oncologist 2010;15(6)556-65

10. WCRF. Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective. Washington: American Institute for Cancer research; 2007

11. Reeves GK, Pirie K, Beral V, et al.: Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study. BMJ 2007 Dec 1; 335(7630): 1134 – Epub 2007 Nov 6

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

13. Andrieu N, Launoy G, Guillois R, Ory-Paoletti C, Gignoux M: Familial relative risk of colorectal cancer: a population-based study. Eur J Cancer 2003;39(13)1904-11

14. IARC. Globocan 2012 Cancer Fact Sheets. 2012. Disponível em http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx

15. Siegel R, Naishadham D, Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1)10-29

16. Souglakos J: Genetic alterations in sporadic and hereditary colorectal cancer: implementations for screening and follow-up. Dig dis 2007;25(1)9-19

17. Johnson IT, Lund EK: Review article: nutrition, obesity and colorectal cancer. Aliment Pharmacol Ther 2007;26(2)161-81

18. Mokdad AH, Marks JS, Stroup DF, Gerberding JL: Actual causes of death in the United States, 2000. JAMA 2004;291(10)1238-45

19. Moore LL, Bradlee ML, Singer MR, et al.: BMI and waist circumference as predictors of lifetime colon cancer risk in Framingham Study adults. Int J Obes Relat Metab Disord 2004;28(4)559-67

20. Gribovskaja-Rupp I, Kosinski L, Ludwig KA: Obesity and colorectal cancer. Clin Colon Rectal Surg 2011;24(4)229-43

21. De Pergola G, Silvestris F: Obesity as a major risk factor for cancer. J Obes 2013;2013:291546

22. WHO. Waist Circumference and Waist–Hip Ratio: Report of a WHO Expert Consultation. Geneva: 2008. Disponível em: http://whqlibdoc.who.int/publications/2011/978 9241501491_eng.pdf

23. IARC. Handbooks of Cancer Prevention. In: Weight Control and Physical Activity. Lyon: 2002

24. Dai Z, Xu YC, Niu L: Obesity and colorectal cancer risk: a meta-analysis of cohort studies. World J Gastroenterol 2007;13(31)4199-206

25. Harriss DJ, Atkinson G, George K, et al.: Lifestyle factors and colorectal cancer risk (1): systematic review and meta-analysis of associations with body mass index. Colorectal Dis 2009;11(6)547-63

26. Moghaddam AA, Woodward M, Huxley R: Obesity and risk of colorectal cancer: a meta-analysis of 31 studies with 70,000 events. Cancer Epidemiol Biomarkers Prev 2007; 16(12)2533-47

27. Larsson SC, Wolk A: Obesity and colon and rectal cancer risk: a meta-analysis of prospective studies. Am J Clin Nutr 2007;86(3)556-65

28. Ning Y, Wang L, Giovannucci EL: A quantitative analysis of body mass index and colorectal cancer: findings from 56 observational studies. Obes Rev 2010;11(1)19-30

29. Ma Y, Yang Y, Wang F, et al.: Obesity and risk of colorectal cancer: a systematic review of prospective studies. PloS One 2013;8(1)e53916

30. Guh DP, Zhang W, Bansback N, Amarsi Z, Birmingham CL, Anis AH: The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis. BMC Public Health 2009;988

31. Le Marchand L, Wilkens LR, Mi MP: Obesity in youth and middle age and risk of colorectal cancer in men. Cancer Causes Control 1992;3(4)349-54

32. Laake I, Thune I, Selmer R, Tretli S, Slattery ML, Veierod MB: A prospective study of body mass index, weight change, and risk of cancer in the proximal and distal colon. Cancer Epidemiol Biomarkers Prev 2010;19(6)1511-22

33. Caan BJ, Coates AO, Slattery ML, Potter JD, Quesenberry CP, JR., Edwards SM: Body size and the risk of colon cancer in a large casecontrol study. Int J Obes Relat Metab Disord 1998;22(2)178 -84

34. Macinnis RJ, English DR, Hopper JL, Haydon AM, Gertig DM, Giles GG: Body size and composition and colon cancer risk in men. Cancer Epidemiol Biomarkers Prev 2004;13(4)553-9

35. Matsuo K, Mizoue T, Tanaka K, et al.: Association between body mass index and the colorectal cancer risk in Japan: pooled analysis of population-based cohort studies in Japan. Ann Oncol 2012;23(2)479-90

36. Nomura A, Heilbrun LK, Stemmermann GN: Body mass index as a predictor of cancer in men. J Natl Cancer Inst 1985;74(2)319-23

37. Thygesen LC, Gronbaek M, Johansen C, Fuchs CS, Willett WC, Giovannucci E: Prospective weight change and colon cancer risk in male US health professionals. Int J Cancer 2008;123(5)1160-5

38. Campbell PT, Cotterchio M, Dicks E, Parfrey P, Gallinger S, McLaughlin JR: Excess body weight and colorectal cancer risk in Canada: associations in subgroups of clinically defined familial risk of cancer. Cancer Epidemiol Biomarkers Prev 2007;16(9)1735-44

39. Bassett JK, Severi G, English DR, et al.: Body size, weight change, and risk of colon cancer. Cancer Epidemiol Biomarkers Prev 2010;19(11)2978 -86

40. Nock NL, Thompson CL, Tucker TC, Berger NA, LI L: Associations between obesity and changes in adult BMI over time and colon cancer risk. Obesity 2008;16(5)1099-104

41. Aleksandrova K, Pischon T, Buijsse B, et al.: Adult weight change and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition. Eur J Cancer 2013;49(16)3526-36

42. Rapp K, Klenk J, Ulmer H, et al.: Weight change and cancer risk in a cohort of more than 65,000 adults in Austria. Ann Oncol 2008;19(4)641-8

43. Steins Bisschop CN, Van Gils CH, Emaus MJ, et al.: Weight change later in life and colon and rectal cancer risk in participants in the EPIC-PANACEA study. Am J Clin Nutr 2014;99(1)139-47

44. Adams TD, Stroup AM, Gress RE, et al.: Cancer incidence and mortality after gastric bypass surgery. Obesity 2009;17(4)796-802

45. Kahn BB, Flier JS: Obesity and insulin resistance. J Clin Invest 2000;106(4)473-81

46. Giovannucci E: Insulin and colon cancer. Cancer Causes Control 1995;6(2)164-79

47. McKeown-Eyssen G: Epidemiology of colorectal cancer revisited: are serum triglycerides and/or plasma glucose associated with risk? Cancer Epidemiol Biomarkers Prev 1994;3(8)687 -95

48. Kahn SE, Hull RL, Utzschneider KM: Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006;444(7121)840-6

49. Sikalidis AK, Varamini B: Roles of hormones and signaling molecules in describing the relationship between obesity and colon cancer. Pathol Oncol Res 2011;17(4)78 5-90

50. Renehan AG, Frystyk J, Flyvbjerg A: Obesity and cancer risk: the role of the insulin-IGF axis. Trends Endocrinol Metab 2006;17(8)328-36

51. Larsson SC, Orsini N, Wolk A: Diabetes mellitus and risk of colorectal cancer: a meta-analysis. J Natl Cancer Inst 2005;97(22)1679-87

52. Giovannucci E: Nutrition, insulin, insulin-like growth factors and cancer. Horm Metab Res 2003;35(11-12)694-704

53. Giovannucci E: Insulin, insulin-like growth factors and colon cancer: a review of the evidence. J Nutr 2001;131(11)3109S-20S

54. Kaaks R, Toniolo P, Akhmedkhanov A, et al.: Serum C-peptide, insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women. J Natl Cancer Inst 2000;92(19)1592-600

55. Schoen RE, Tangen CM, Kuller LH, et al : Increased blood glucose and insulin, body size, and incident colorectal cancer. J Natl Cancer Inst 1999;91(13)1147-54

56. Michaud DS, Fuchs CS, Liu S, Willett WC, Colditz GA, Giovannucci E: Dietary glycemic load, carbohydrate, sugar, and colorectal cancer risk in men and women. Cancer Epidemiol Biomarkers Prev 2005;14(1)138-47

57. Donohoe CL, Doyle SL, Reynolds JV: Visceral adiposity, insulin resistance and cancer risk. Diabetol Metab Syndr 2011;3:12

58. Warren RS, Yuan H, Matli MR, Ferrara N, Donner DB: Induction of vascular endothelial growth factor by insulin-like growth factor 1 in colorectal carcinoma. J Biol Chem 1996;271(46)29483-8

59. Renehan AG, Zwahlen M, Minder C, O’Dwyer ST, Shalet SM, Egger M: Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet 2004;363(9418)1346-53

60. Wei EK, Ma J, Pollak MN, et al: A prospective study of C-peptide, insulin-like growth factor-I, insulin-like growth factor binding protein-1, and the risk of colorectal cancer in women. Cancer Epidemiol Biomarkers Prev 2005;14(4)850-5

61. Ouban A, Muraca P, Yeatman T, Coppola D: Expression and distribution of insulin-like growth factor-1 receptor in human carcinomas.
Hum Pathol 2003;34(8)803-8

62. Yavari K, Taghikhani M, Ghannadi Maragheh M, Mesbah-Namin SA, Babaei MH: Downregulation of IGF-IR expression by RNAi inhibits proliferation and enhances chemosensitization of human colon cancer cells. Int J Colorectal Dis 2010;25(1)9-16

63. Rokkas T, Pistiolas D, Sechopoulos P, Margantinis G, Koukoulis G: Risk of colorectal neoplasm in patients with acromegaly: a metaanalysis. World J Gastroenterol 2008;14(22)3484-9

64. Juul A, Bang P, Hertel NT, et al.: Serum insulin-like growth factor-I in 1030 healthy children, adolescents, and adults: relation to age, sex, stage of puberty, testicular size, and body mass index. J Clin Endocrinol Metab 1994;78 (3)744-52

65. Amemori S, Ootani A, Aoki S, et al.: Adipocytes and preadipocytes promote the proliferation of colon cancer cells in vitro. Am J Physiol Gastrointest Liver Physiol 2007;292(3)G923-9

66. Gonullu G, Kahraman H, Bedir A, Bektas A, Yucel I: Association between adiponectin, resistin, insulin resistance, and colorectal tumors. Int J Colorectal Dis 2010;25(2)205-12

67. Jaffe T, Schwartz B: Leptin promotes motility and invasiveness in human colon cancer cells by activating multiple signal-transduction pathways. Int J Cancer 2008;123(11)2543-56

68. Laughlin GA, Barrett-Connor E, May S: Sex-specific association of the androgen to oestrogen ratio with adipocytokine levels in older adults: the Rancho Bernardo Study. Clin endocrinol 2006;65(4)506-13

69. Shehzad A, Iqbal W, Shehzad O, Lee YS: Adiponectin: regulation of its production and its role in human diseases. Hormones 2012;11(1)8-20

70. Dalamaga M, Diakopoulos KN, Mantzoros CS: The role of adiponectin in cancer: a review of current evidence. Endocr Rev 2012;33(4)547-94

71. Renehan AG, Roberts DL, Dive C: Obesity and cancer: pathophysiological and biological mechanisms. Arch Physiol Biochem 2008;114(1)71-83

72. Moon HS, Liu X, Nagel JM, et al.: Salutary effects of adiponectin on colon cancer: in vivo and in vitro studies in mice. Gut 2013;62(4)561-70

73. Sugiyama M, Takahashi H, Hosono K, et al.: Adiponectin inhibits colorectal cancer cell growth through the AMPK/mTOR pathway. Int J Oncol 2009;34(2)339-44

74. Sun Y, Lodish HF: Adiponectin deficiency promotes tumor growth in mice by reducing macrophage infiltration. PloS one 2010; 5(8)e11987

75. Wei EK, Giovannucci E, Fuchs CS, Willett WC, Mantzoros CS: Low plasma adiponectin levels and risk of colorectal cancer in men: a prospective study. J Natl Cancer Inst 2005;97(22)1688 -94

76. Song M, Zhang X, Wu K, et al.: Plasma adiponectin and soluble leptin receptor and risk of colorectal cancer: a prospective study. Cancer Prev Res 2013;6(9)87 5-85

77 . Xu XT, Xu Q, Tong JL, et al.: Meta-analysis: circulating adiponectin levels and risk of colorectal cancer and adenoma. J Dig Dis 2011;12(4)234-44

78 . Lukanova A, Soderberg S, Kaaks R, Jellum E, Stattin P: Serum adiponectin is not associated with risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev 2006;15(2)401-2

79. Svobodova S, Topolcan O, Holubec L, JR., Levy M, Pecen L, Svacina S: Parameters of biological activity in colorectal cancer. Anticancer res 2011;31(1)373-8

80. Hardwick JC, Van Den Brink GR, Offerhaus GJ, Van Deventer SJ, Peppelenbosch MP: Leptin is a growth factor for colonic epithelial cells. Gastroenterol 2001;121(1)79-90

81. Kelesidis T, Kelesidis I, Chou S, Mantzoros CS: Narrative review: the role of leptin in human physiology: emerging clinical applications. Ann Intern Med 2010;152(2)93-100

82. Stattin P, Lukanova A, Biessy C, et al.: Obesity and colon cancer: does leptin provide a link? Int J Cancer 2004;109(1)149-52

83. Attoub S, Noe V, Pirola L, et al.: Leptin promotes invasiveness of kidney and colonic epithelial cells via phosphoinositide 3-kinase-, rho-, and rac-dependent signaling pathways. FASEB journal 2000;14(14)2329-38

84. Stattin P, Palmqvist R, Soderberg S, et al.: Plasma leptin and colorectal cancer risk: a prospective study in Northern Sweden. Oncol rep 2003;10(6)2015-21

85. Tamakoshi K, Toyoshima H, Wakai K, et al.: Leptin is associated with an increased female colorectal cancer risk: a nested case-control study in Japan. Oncology 2005;68(4-6)454-61

86. Ho GY, Wang T, Gunter MJ, et al.: Adipokines linking obesity with colorectal cancer risk in postmenopausal women. Cancer research 2012;72(12)3029-37

87. Wallace AM, Sattar N, MCMillan DC: Effect of weight loss and the inflammatory response on leptin concentrations in gastrointestinal cancer patients. Clin cancer res 1998;4(12)2977-9

88. Arpaci F, Yilmaz MI, Ozet A, et al.: Low serum leptin level in colon cancer patients without significant weight loss. Tumori 2002;88 (2)147-9

89. John BJ, Irukulla S, Abulafi AM, Kumar D, Mendall MA: Systematic review: adipose tissue, obesity and gastrointestinal diseases. Aliment Pharmacol Ther 2006;23(11)1511-23

90. Dalgleish AG, O’Byrne K: Inflammation and cancer: the role of the immune response and angiogenesis. Cancer treat res 2006;1301-38

91. Ullman TA, Itzkowitz SH: Intestinal inflammation and cancer. Gastroenterol 2011;140(6)1807-16

92. Cani PD, Osto M, Geurts L, Everard A: Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity. Gut microbes 2012;3(4)279-88

93. Serino M, Luche E, Gres S, et al.: Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiota. Gut 2012;61(4)543-53

94. Chan AT, Ogino S, Giovannucci EL, Fuchs CS: Inflammatory markers are associated with risk of colorectal cancer and chemopreventive response to anti-inflammatory drugs. Gastroenterol 2011;140(3)799-808

95. Lund EK, Belshaw NJ, Elliott GO, Johnson IT: Recent advances in understanding the role of diet and obesity in the development of colorectal cancer. Proc Nutr Soc 2011;70(2)194-204

96. Muller M, Den Tonkelaar I, Thijssen JH, Grobbee DE, Van Der Schouw YT: Endogenous sex hormones in men aged 40-80 years. Eur J
Endocrinol 2003;149(6)583-9

97. Bezemer ID, Rinaldi S, Dossus L, et al.: C-peptide, IGF-I, sex-steroid hormones and adiposity: a cross-sectional study in healthy women within the European Prospective Investigation into Cancer and Nutrition (EPIC). Cancer causes control 2005;16(5)561-72

98. Smith MR, Lee H, Nathan DM: Insulin sensitivity during combined androgen blockade for prostate cancer. J Clin Endocrinol Metab
2006;91(4)1305-8

99. Marin P, Holmang S, Jonsson L, et al.: The effects of testosterone treatment on body composition and metabolism in middle-aged obese men. Int J Obes Relat Metab Disord 1992;16(12)991-7

100. Ding EL, Song Y, Malik VS, Liu S: Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and metaanalysis.
JAMA 2006;295(11)1288 -99

101. Gu S, Papadopoulou N, Gehring EM, et al.: Functional membrane androgen receptors in colon tumors trigger pro-apoptotic responses in vitro and reduce drastically tumor incidence in vivo. Mol cancer 2009;8114

102. Slattery ML, Ballard-Barbash R, Edwards S, Caan BJ, Potter JD: Body mass index and colon cancer: an evaluation of the modifying effects of estrogen (United States). Cancer causes control 2003;14(1)75-84

103. Terry PD, Miller AB, Rohan TE: Obesity and colorectal cancer risk in women. Gut 2002;51(2)191-4

104. Hou L, Ji BT, Blair A, et al.: Body mass index and colon cancer risk in Chinese people: menopause as an effect modifier. Eur J Cancer 2006;42(1)84-90

105. Bardou M, Barkun AN, Martel M: Obesity and colorectal cancer. Gut 2013;62(6)933-47

106. Sinicrope FA, Foster NR, Sargent DJ, O’Connell MJ, Rankin C: Obesity is an independent prognostic variable in colon cancer survivors. Clin cancer res 2010;16(6)188 4-93

107. Shtivelband MI, Juneja HS, Lee S, Wu KK: Aspirin and salicylate inhibit colon cancer medium- and VEGF-induced endothelial tube formation: correlation with suppression of cyclooxygenase-2 expression. J Thromb Haemost 2003; 1(10):2225-33

108. Bellows CF, Zhang Y, Chen J, Frazier ML, Kolonin MG: Circulation of progenitor cells in obese and lean colorectal cancer patients. Cancer Epidemiol Biomarkers Prev 2011;20(11)2461-8
Published
2017-09-30
How to Cite
SIMÕES, Maria Leonor Táboas; BARBOSA, Laura E.. Obesity: impact on Colorectal Carcinoma. Revista Portuguesa de Cirurgia, [S.l.], n. 42, p. 17 - 32, sep. 2017. ISSN 2183-1165. Available at: <https://revista.spcir.com/index.php/spcir/article/view/679>. Date accessed: 03 july 2024.
Section
Original Papers