Obesity and colorectal cancer: Molecular features of adipose tissue

Journal of Translational Medicine

Volumn 14, Issue 1, 2016, Pages

  Martinez Useros, Javier ^a   Garcia Foncillas, Jesus ^a  

^a UAM)   (Spain)

Author keywords

4 HNE; Adipose tissue; BMI; Colorectal cancer; Cytokines; Inflammation; MDA; MPE; Obesity; Overweight

Indexed keywords

ADIPONECTIN; COLLAGEN TYPE 6; ENDOTROPHIN; GAMMA INTERFERON INDUCIBLE PROTEIN 10; INTERLEUKIN 2; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 6; INTERLEUKIN 8; LACTATE DEHYDROGENASE; LEPTIN; PROSTAGLANDIN E2; SOMATOMEDIN C; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

BODY MASS; CANCER SURVIVAL; CARCINOGENESIS; COLORECTAL CANCER; CYTOKINE PRODUCTION; DISEASE ASSOCIATION; DISEASE FREE SURVIVAL; DNA SYNTHESIS; FATTY ACID SYNTHESIS; HUMAN; INSULIN RESISTANCE; INTRAABDOMINAL FAT; LIPID PEROXIDATION; NONHUMAN; OBESITY; OVERALL SURVIVAL; OXIDATIVE STRESS; PROTEIN EXPRESSION; REVIEW; UPREGULATION; WAIST CIRCUMFERENCE; WAIST HIP RATIO; ADIPOSE TISSUE; COLORECTAL TUMOR; COMPLICATION; INFLAMMATION; PATHOLOGY;

ADIPOSE TISSUE; COLORECTAL NEOPLASMS; HUMANS; INFLAMMATION; OBESITY;

EID: 84955408177     PISSN: None     EISSN: 14795876     Source Type: Journal    
DOI: 10.1186/s12967-016-0772-5     Document Type: Review

References (201)

1. Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA. 2014;311(8):806-14.
2. Parkin DM, Boyd L, Walker LC. 16. The fraction of cancer attributable to lifestyle and environmental factors in the UK in 2010. Br J Cancer. 2011;2011(6):489.
3. Chan DS, Vieira AR, Aune D, Bandera EV, Greenwood DC, 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.
4. Arem H, Chlebowski R, Stefanick ML, Anderson G, Wactawski-Wende J, Sims S, et al. Body mass index, physical activity, and survival after endometrial cancer diagnosis: results from the Women's Health Initiative. Gynecol Oncol. 2013;128(2):181-6.
5. Leung C, Yeoh SW, Patrick D, Ket S, Marion K, Gow P, et al. Characteristics of hepatocellular carcinoma in cirrhotic and non-cirrhotic non-alcoholic fatty liver disease. World J Gastroenterol. 2015;21(4):1189-96.
6. Parkin E, O'Reilly DA, Sherlock DJ, Manoharan P, Renehan AG. Excess adiposity and survival in patients with colorectal cancer: a systematic review. Obes Rev. 2014;15(5):434-51.
7. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5-29. doi: 10.3322/caac.21254.
8. Chan DS, Lau R, Aune D, Vieira R, Greenwood DC, Kampman E, et al. Red and processed meat and colorectal cancer incidence: meta-analysis of prospective studies. PLoS One. 2011;6(6):6.
9. Meyerhardt JA, Sato K, Niedzwiecki D, Ye C, Saltz LB, Mayer RJ, et al. Dietary glycemic load and cancer recurrence and survival in patients with stage III colon cancer: findings from CALGB 89803. J Natl Cancer Inst. 2012;104(22):1702-11.
10. Fuchs MA, Sato K, Niedzwiecki D, Ye X, Saltz LB, Mayer RJ, et al. Sugar-sweetened beverage intake and cancer recurrence and survival in CALGB 89803 (Alliance). PLoS One. 2014;9(6):2014.
11. Rosati R, Ma H, Cabelof DC. Folate and colorectal cancer in rodents: a model of DNA repair deficiency. J Oncol. 2012;2012(105949):9.
12. Leclerc D, Dejgaard K, Mazur A, Deng L, Wu Q, Nilsson T, et al. Quantitative proteomics reveals differentially expressed proteins in murine preneoplastic intestine in a model of intestinal tumourigenesis induced by low dietary folate and MTHFR deficiency. Proteomics. 2014;14(21-22):2558-65.
13. Koshy G, Delpisheh A, Brabin BJ. Dose response association of pregnancy cigarette smoke exposure, childhood stature, overweight and obesity. Eur J Public Health. 2011;21(3):286-91.
14. Cupul-Uicab LA, Skjaerven R, Haug K, Melve KK, Engel SM, Longnecker MP. In utero exposure to maternal tobacco smoke and subsequent obesity, hypertension, and gestational diabetes among women in the MoBa cohort. Environ Health Perspect. 2012;120(3):355-60.
15. Kim HW, Kam S, Lee DH. Synergistic interaction between polycyclic aromatic hydrocarbons and environmental tobacco smoke on the risk of obesity in children and adolescents: the U.S. National Health and Nutrition Examination Survey 2003-2008. Environ Res. 2014;135:354-60.
16. Yang CM, Lee IT, Lin CC, Yang YL, Luo SF, Kou YR, et al. Cigarette smoke extract induces COX-2 expression via a PKCalpha/c-Src/EGFR, PDGFR/PI3 K/Akt/NF-kappaB pathway and p300 in tracheal smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2009;297(5):28.
17. Pai R, Soreghan B, Szabo IL, Pavelka M, Baatar D, Tarnawski AS. Prostaglandin E2 transactivates EGF receptor: a novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy. Nat Med. 2002;8(3):289-93.
18. Castellone MD, Teramoto H, Williams BO, Druey KM, Gutkind JS. Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-beta-catenin signaling axis. Science. 2005;310(5753):1504-10.
19. Martinez ME, Heddens D, Earnest DL, Bogert CL, Roe D, Einspahr J, et al. Physical activity, body mass index, and prostaglandin E2 levels in rectal mucosa. J Natl Cancer Inst. 1999;91(11):950-3.
20. Kuchiba A, Morikawa T, Yamauchi M, Imamura Y, Liao X, Chan AT, et al. Body mass index and risk of colorectal cancer according to fatty acid synthase expression in the nurses' health study. J Natl Cancer Inst. 2012;104(5):415-20.
21. Morikawa T, Kuchiba A, Lochhead P, Nishihara R, Yamauchi M, Imamura Y, et al. Prospective analysis of body mass index, physical activity, and colorectal cancer risk associated with beta-catenin (CTNNB1) status. Cancer Res. 2013;73(5):1600-10.
22. Tandon K, Imam M, Ismail BE, Castro F. Body mass index and colon cancer screening: the road ahead. World J Gastroenterol. 2015;21(5):1371-6. doi: 10.3748/wjg.v21.i5.1371.
23. Olefsky JM, Glass CK. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol. 2010;72:219-46.
24. Mirza RE, Koh TJ. Contributions of cell subsets to cytokine production during normal and impaired wound healing. Cytokine. 2015;71(2):409-12.
25. Karin M, Greten FR. NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol. 2005;5(10):749-59.
26. Ashwell M, Gunn P, Gibson S. Waist-to-height ratio is a better screening tool than waist circumference and BMI for adult cardiometabolic risk factors: systematic review and meta-analysis. Obes Rev. 2012;13(3):275-86.
27. Schneider HJ, Friedrich N, Klotsche J, Pieper L, Nauck M, John U, et al. The predictive value of different measures of obesity for incident cardiovascular events and mortality. J Clin Endocrinol Metab. 2010;95(4):1777-85.
28. DGSP. S 1-Leitlinie Vorsorgeuntersuchung im Sport. 2007.
29. Song M, Hu FB, Spiegelman D, Chan AT, Wu K, Ogino S, et al. Long-term status and change of body fat distribution, and risk of colorectal cancer: a prospective cohort study. Int J Epidemiol. 2015. doi: 10.1093/ije/dyv177.
30. Volgyi E, Tylavsky FA, Lyytikainen A, Suominen H, Alen M, Cheng S. Assessing body composition with DXA and bioimpedance: effects of obesity, physical activity, and age. Obesity. 2008;16(3):700-5.
31. Amato MC, Giordano C. Visceral adiposity index: an indicator of adipose tissue dysfunction. Int J Endocrinol. 2014;2014(730827):14.
32. Choe EK, Kim D, Kim HJ, Park KJ. Association of visceral obesity and early colorectal neoplasia. World J Gastroenterol. 2013;19(45):8349-56.
33. Park SW, Lee HL, Doo EY, Lee KN, Jun DW, Lee OY, et al. Visceral obesity predicts fewer lymph node metastases and better overall survival in colon cancer. J Gastrointest Surg. 2015;19(8):1513-21.
34. Fujioka S, Matsuzawa Y, Tokunaga K, Tarui S. Contribution of intra-abdominal fat accumulation to the impairment of glucose and lipid metabolism in human obesity. Metabolism. 1987;36(1):54-9.
35. Malietzis G, Aziz O, Bagnall NM, Johns N, Fearon KC, Jenkins JT. The role of body composition evaluation by computerized tomography in determining colorectal cancer treatment outcomes: a systematic review. Eur J Surg Oncol. 2015;41(2):186-96.
36. Kang SM, Yoon JW, Ahn HY, Kim SY, Lee KH, Shin H, et al. Android fat depot is more closely associated with metabolic syndrome than abdominal visceral fat in elderly people. PLoS One. 2011;6(11):11.
37. Fox CS, Massaro JM, Hoffmann U, Pou KM, Maurovich-Horvat P, Liu CY, et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation. 2007;116(1):39-48.
38. WHO_Expert_Committee. Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. Geneva: World Health Organization Technical Report Series; 1995.
39. Murphy TK, Calle EE, Rodriguez C, Kahn HS, Thun MJ. Body mass index and colon cancer mortality in a large prospective study. Am J Epidemiol. 2000;152(9):847-54.
40. Graham S, Marshall J, Haughey B, Mittelman A, Swanson M, Zielezny M, et al. Dietary epidemiology of cancer of the colon in western New York. Am J Epidemiol. 1988;128(3):490-503.
41. de Verdier MG, Hagman U, Steineck G, Rieger A, Norell SE. Diet, body mass and colorectal cancer: a case-referent study in Stockholm. Int J Cancer. 1990;46(5):832-8.
42. Kune GA, Kune S, Watson LF. Body weight and physical activity as predictors of colorectal cancer risk. Nutr Cancer. 1990;13(1-2):9-17.
43. Le Marchand L, Wilkens LR, Kolonel LN, Hankin JH, Lyu LC. Associations of sedentary lifestyle, obesity, smoking, alcohol use, and diabetes with the risk of colorectal cancer. Cancer Res. 1997;57(21):4787-94.
44. Caan BJ, Coates AO, Slattery ML, Potter JD, Quesenberry CP Jr, Edwards SM. Body size and the risk of colon cancer in a large case-control study. Int J Obes Relat Metab Disord. 1998;22(2):178-84.
45. Russo A, Franceschi S, La Vecchia C, Dal Maso L, Montella M, Conti E, et al. Body size and colorectal-cancer risk. Int J Cancer. 1998;78(2):161-5.
46. Zhang X, Wu K, Giovannucci EL, Ma J, Colditz GA, Fuchs CS, et al. Early life body fatness and risk of colorectal cancer in US Women and men-results from two large cohort studies. Cancer Epidemiol Biomark Prev. 2015;24(4):690-7.
47. Dietz AT, Newcomb PA, Marcus PM, Storer BE. The association of body size and large bowel cancer risk in Wisconsin (United States) women. Cancer Causes Control. 1995;6(1):30-6.
48. Ashktorab H, Paydar M, Yazdi S, Namin HH, Sanderson A, Begum R, et al. BMI and the risk of colorectal adenoma in African-Americans. Obesity. 2014;22(5):1387-91.
49. Nagata N, Sakamoto K, Arai T, Niikura R, Shimbo T, Shinozaki M, et al. Visceral abdominal fat measured by computed tomography is associated with an increased risk of colorectal adenoma. Int J Cancer. 2014;135(10):2273-81.
50. Liesenfeld DB, Grapov D, Fahrmann JF, Salou M, Scherer D, Toth R, et al. Metabolomics and transcriptomics identify pathway differences between visceral and subcutaneous adipose tissue in colorectal cancer patients: the ColoCare study. Am J Clin Nutr. 2015;102(2):433-43.
51. Schoen RE, Weissfeld JL, Kuller LH, Thaete FL, Evans RW, Hayes RB, et al. Insulin-like growth factor-I and insulin are associated with the presence and advancement of adenomatous polyps. Gastroenterology. 2005;129(2):464-75.
52. Lee CS, Murphy DJ, McMahon C, Nolan B, Cullen G, Mulcahy H, et al. Visceral adiposity is a risk factor for poor prognosis in colorectal cancer patients receiving adjuvant chemotherapy. J Gastrointest Cancer. 2015;46(3):243-50.
53. Santarpia L, Contaldo F, Pasanisi F. Nutritional screening and early treatment of malnutrition in cancer patients. J Cachexia Sarcopenia Muscle. 2011;2(1):27-35.
54. Bozzetti F. Nutritional support of the oncology patient. Crit Rev Oncol Hematol. 2013;87(2):172-200.
55. Thrift AP, Gong J, Peters U, Chang-Claude J, Rudolph A, Slattery ML, et al. Mendelian randomization study of body mass index and colorectal cancer risk. Cancer Epidemiol Biomark Prev. 2015;2015:14.
56. Yin H, Xu L, Porter NA. Free radical lipid peroxidation: mechanisms and analysis. Chem Rev. 2011;111(10):5944-72.
57. Kinnunen PK, Kaarniranta K, Mahalka AK. Protein-oxidized phospholipid interactions in cellular signaling for cell death: from biophysics to clinical correlations. Biochim Biophys Acta. 2012;2012(10):2446-55.
58. Fruhwirth GO, Loidl A, Hermetter A. Oxidized phospholipids: from molecular properties to disease. Biochim Biophys Acta. 2007;7:718-36.
59. Esterbauer H, Eckl P, Ortner A. Possible mutagens derived from lipids and lipid precursors. Mutat Res. 1990;238(3):223-33.
60. Brambilla G, Sciaba L, Faggin P, Maura A, Marinari UM, Ferro M, et al. Cytotoxicity, DNA fragmentation and sister-chromatid exchange in Chinese hamster ovary cells exposed to the lipid peroxidation product 4-hydroxynonenal and homologous aldehydes. Mutat Res. 1986;171(2-3):169-76.
61. Zarkovic N. 4-hydroxynonenal as a bioactive marker of pathophysiological processes. Mol Aspects Med. 2003;24(4-5):281-91.
62. Shaulian E. AP-1-The Jun proteins: oncogenes or tumour suppressors in disguise? Cell Signal. 2010;22(6):894-9.
63. Morgan MJ, Liu ZG. Crosstalk of reactive oxygen species and NF-kappaB signaling. Cell Res. 2011;21(1):103-15.
64. Ahmadian M, Suh JM, Hah N, Liddle C, Atkins AR, Downes M, et al. PPARgamma signaling and metabolism: the good, the bad and the future. Nat Med. 2013;19(5):557-66.
65. Wang Z, Dou X, Gu D, Shen C, Yao T, Nguyen V, et al. 4-Hydroxynonenal differentially regulates adiponectin gene expression and secretion via activating PPARgamma and accelerating ubiquitin-proteasome degradation. Mol Cell Endocrinol. 2012;349(2):222-31.
66. Shu L, Huang R, Wu S, Chen Z, Sun K, Jiang Y, et al. PPAR gamma and its ligands, potential anti-tumour agents in the digestive system. Curr Stem Cell Res Ther. 2015;2015:30.
67. Kwon KA, Yun J, Oh SY, Seo BG, Lee S, Lee JH, et al. Clinical significance of peroxisome proliferator-activated Receptor gamma and TRAP220 in patients with operable colorectal cancer. Cancer Res Treat. 2015;2015(23):024.
68. Pang T, Kaufman A, Choi J, Gill A, Drummond M, Hugh T, et al. Peroxisome proliferator-activated receptor-alpha staining is associated with worse outcome in colorectal liver metastases. Mol Clin Oncol. 2015;3(2):308-16.
69. Shi Q, Vaillancourt F, Cote V, Fahmi H, Lavigne P, Afif H, et al. Alterations of metabolic activity in human osteoarthritic osteoblasts by lipid peroxidation end product 4-hydroxynonenal. Arthritis Res Ther. 2006;8(6):R159.
70. Uchida K, Kumagai T. 4-hydroxy-2-nonenal as a COX-2 inducer. Mol Aspects Med. 2003;24(4-5):213-8.
71. Kaidi A, Qualtrough D, Williams AC, Paraskeva C. Direct transcriptional up-regulation of cyclooxygenase-2 by hypoxia-inducible factor (HIF)-1 promotes colorectal tumour cell survival and enhances HIF-1 transcriptional activity during hypoxia. Cancer Res. 2006;66(13):6683-91.
72. Sanchez-de-Abajo A, de la Hoya M, van Puijenbroek M, Tosar A, Lopez-Asenjo JA, Diaz-Rubio E, et al. Molecular analysis of colorectal cancer tumours from patients with mismatch repair proficient hereditary nonpolyposis colorectal cancer suggests novel carcinogenic pathways. Clin Cancer Res. 2007;13(19):5729-35.
73. Slattery ML, Lundgreen A, Wolff RK. MAP kinase genes and colon and rectal cancer. Carcinogenesis. 2012;33(12):2398-408.
74. Luo F, Poulogiannis G, Ye H, Hamoudi R, Zhang W, Dong G, et al. Mutant K-ras promotes carcinogen-induced murine colorectal tumourigenesis, but does not alter tumour chromosome stability. J Pathol. 2011;223(3):390-9.
75. Cantwell-Dorris ER, O'Leary JJ, Sheils OM. BRAFV600E: implications for carcinogenesis and molecular therapy. Mol Cancer Ther. 2011;10(3):385-94.
76. Chalhoub N, Baker SJ. PTEN and the PI3-kinase pathway in cancer. Annu Rev Pathol. 2009;4:127-50.
77. Sahin IH, Oktay AA. EGFR signaling and oncogenic pathway signature in colorectal cancer. Gut. 2013;62(11):1670. doi: 10.1136/gutjnl-2013-304781(Epub 2013).
78. Paola D, Domenicotti C, Nitti M, Vitali A, Borghi R, Cottalasso D, et al. Oxidative stress induces increase in intracellular amyloid beta-protein production and selective activation of betaI and betaII PKCs in NT2 cells. Biochem Biophys Res Commun. 2000;268(2):642-6.
79. Cooke MS, Evans MD, Dizdaroglu M, Lunec J. Oxidative DNA damage: mechanisms, mutation, and disease. Faseb J. 2003;17(10):1195-214.
80. Savio M, Stivala LA, Bianchi L, Vannini V, Prosperi E. Involvement of the proliferating cell nuclear antigen (PCNA) in DNA repair induced by alkylating agents and oxidative damage in human fibroblasts. Carcinogenesis. 1998;19(4):591-6.
81. Barcelos RC, Vey LT, Segat HJ, Roversi K, Dias VT, Trevizol F, et al. Cross-generational trans fat intake exacerbates UV radiation-induced damage in rat skin. Food Chem Toxicol. 2014;69:38-45.
82. Murray AR, Kisin E, Castranova V, Kommineni C, Gunther MR, Shvedova AA. Phenol-induced in vivo oxidative stress in skin: evidence for enhanced free radical generation, thiol oxidation, and antioxidant depletion. Chem Res Toxicol. 2007;20(12):1769-77.
83. Pongnimitprasert N, Hurtado M, Lamari F, El Benna J, Dupuy C, Fay M, et al. Implication of NADPH oxidases in the early inflammation process generated by cystic fibrosis cells. ISRN Inflamm. 2012;2012(481432):2012.
84. Niedernhofer LJ, Daniels JS, Rouzer CA, Greene RE, Marnett LJ. Malondialdehyde, a product of lipid peroxidation, is mutagenic in human cells. J Biol Chem. 2003;278(33):31426-33.
85. Wang M, Dhingra K, Hittelman WN, Liehr JG, de Andrade M, Li D. Lipid peroxidation-induced putative malondialdehyde-DNA adducts in human breast tissues. Cancer Epidemiol Biomark Prev. 1996;5(9):705-10.
86. Wang X, Lei XG, Wang J. Malondialdehyde regulates glucose-stimulated insulin secretion in murine islets via TCF7L2-dependent Wnt signaling pathway. Mol Cell Endocrinol. 2014;382(1):8-16.
87. Blair IA. DNA adducts with lipid peroxidation products. J Biol Chem. 2008;283(23):15545-9.
88. Garcia SC, Grotto D, Bulcao RP, Moro AM, Roehrs M, Valentini J, et al. Evaluation of lipid damage related to pathological and physiological conditions. Drug Chem Toxicol. 2013;36(3):306-12.
89. Shanmugam N, Figarola JL, Li Y, Swiderski PM, Rahbar S, Natarajan R. Proinflammatory effects of advanced lipoxidation end products in monocytes. Diabetes. 2008;57(4):879-88.
90. Merendino RA, Salvo F, Saija A, Di Pasquale G, Tomaino A, Minciullo PL, et al. Malondialdehyde in benign prostate hypertrophy: a useful marker? Mediators Inflamm. 2003;12(2):127-8.
91. Bartoli ML, Novelli F, Costa F, Malagrino L, Melosini L, Bacci E, et al. Malondialdehyde in exhaled breath condensate as a marker of oxidative stress in different pulmonary diseases. Mediators Inflamm. 2011;2011(891752):16.
92. Marnett LJ. Oxy radicals, lipid peroxidation and DNA damage. Toxicology. 2002;182:219-22.
93. Sram RJ, Farmer P, Singh R, Garte S, Kalina I, Popov TA, et al. Effect of vitamin levels on biomarkers of exposure and oxidative damage-the EXPAH study. Mutat Res. 2009;672(2):129-34.
94. Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, et al. Genetic alterations during colorectal-tumour development. N Engl J Med. 1988;319(9):525-32.
95. Rex DK, Ahnen DJ, Baron JA, Batts KP, Burke CA, Burt RW, et al. Serrated lesions of the colorectum: review and recommendations from an expert panel. Am J Gastroenterol. 2012;107(9):1315-29.
96. Colussi D, Brandi G, Bazzoli F, Ricciardiello L. Molecular pathways involved in colorectal cancer: implications for disease behavior and prevention. Int J Mol Sci. 2013;14(8):16365-85.
97. Fearon ER BG. Molecular biology of colorectal cancer. In: DeVita VT Jr LT, Rosenberg SA, editors. De- Vita, Hellman, and Rosenberg's cancer: principles & practice of oncology. Philadelphia: Lippincott Williams & Wilkins; 2008.
98. Xu K, Shu HK. EGFR activation results in enhanced cyclooxygenase-2 expression through p38 mitogen-activated protein kinase-dependent activation of the Sp1/Sp3 transcription factors in human gliomas. Cancer Res. 2007;67(13):6121-9.
99. Cha YI, DuBois RN. NSAIDs and cancer prevention: targets downstream of COX-2. Annu Rev Med. 2007;58:239-52.
100. Wang D, Fu L, Sun H, Guo L, DuBois RN. Prostaglandin E promotes colorectal cancer stem cell expansion and metastasis in mice. Gastroenterology. 2015;149(7):1884-95.
101. Fearon ER, Vogelstein B. A genetic model for colorectal tumourigenesis. Cell. 1990;61(5):759-67.
102. Lynch HT, Lynch JF, Lynch PM, Attard T. Hereditary colorectal cancer syndromes: molecular genetics, genetic counseling, diagnosis and management. Fam Cancer. 2008;7(1):27-39.
103. Goss KH, Groden J. Biology of the adenomatous polyposis coli tumour suppressor. J Clin Oncol. 2000;18(9):1967-79.
104. Newton K, Jorgensen NM, Wallace AJ, Buchanan DD, Lalloo F, McMahon RF, et al. Tumour MLH1 promoter region methylation testing is an effective prescreen for Lynch Syndrome (HNPCC). J Med Genet. 2014;51(12):789-96.
105. Papadopoulos N, Nicolaides NC, Wei YF, Ruben SM, Carter KC, Rosen CA, et al. Mutation of a mutL homolog in hereditary colon cancer. Science. 1994;263(5153):1625-9.
106. Bronner CE, Baker SM, Morrison PT, Warren G, Smith LG, Lescoe MK, et al. Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature. 1994;368(6468):258-61.
107. Fujiwara T, Stolker JM, Watanabe T, Rashid A, Longo P, Eshleman JR, et al. Accumulated clonal genetic alterations in familial and sporadic colorectal carcinomas with widespread instability in microsatellite sequences. Am J Pathol. 1998;153(4):1063-78.
108. Poulogiannis G, Frayling IM, Arends MJ. DNA mismatch repair deficiency in sporadic colorectal cancer and Lynch syndrome. Histopathology. 2010;56(2):167-79.
109. Ji HP, King MC. A functional assay for mutations in tumour suppressor genes caused by mismatch repair deficiency. Hum Mol Genet. 2001;10(24):2737-43.
110. Baker SJ, Preisinger AC, Jessup JM, Paraskeva C, Markowitz S, Willson JK, et al. p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumourigenesis. Cancer Res. 1990;50(23):7717-22.
111. Ionov Y, Yamamoto H, Krajewski S, Reed JC, Perucho M. Mutational inactivation of the proapoptotic gene BAX confers selective advantage during tumour clonal evolution. Proc Natl Acad Sci USA. 2000;97(20):10872-7.
112. Trojan J, Brieger A, Raedle J, Weber N, Kriener S, Kronenberger B, et al. BAX and caspase-5 frameshift mutations and spontaneous apoptosis in colorectal cancer with microsatellite instability. Int J Colorectal Dis. 2004;19(6):538-44.
113. Mrozek A, Petrowsky H, Sturm I, Kraus J, Hermann S, Hauptmann S, et al. Combined p53/Bax mutation results in extremely poor prognosis in gastric carcinoma with low microsatellite instability. Cell Death Differ. 2003;10(4):461-7.
114. Veigl ML, Kasturi L, Olechnowicz J, Ma AH, Lutterbaugh JD, Periyasamy S, et al. Biallelic inactivation of hMLH1 by epigenetic gene silencing, a novel mechanism causing human MSI cancers. Proc Natl Acad Sci USA. 1998;95(15):8698-702.
115. Slattery ML, Curtin K, Anderson K, Ma KN, Ballard L, Edwards S, et al. Associations between cigarette smoking, lifestyle factors, and microsatellite instability in colon tumours. J Natl Cancer Inst. 2000;92(22):1831-6.
116. Satia JA, Keku T, Galanko JA, Martin C, Doctolero RT, Tajima A, et al. Diet, lifestyle, and genomic instability in the North Carolina Colon Cancer Study. Cancer Epidemiol Biomark Prev. 2005;14(2):429-36.
117. Campbell PT, Jacobs ET, Ulrich CM, Figueiredo JC, Poynter JN, McLaughlin JR, et al. Case-control study of overweight, obesity, and colorectal cancer risk, overall and by tumour microsatellite instability status. J Natl Cancer Inst. 2010;102(6):391-400.
118. Bos JL, Fearon ER, Hamilton SR, Verlaan-de Vries M, van Boom JH, van der Eb AJ, et al. Prevalence of ras gene mutations in human colorectal cancers. Nature. 1987;327(6120):293-7.
119. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949-54.
120. Rajagopalan H, Bardelli A, Lengauer C, Kinzler KW, Vogelstein B, Velculescu VE. Tumourigenesis: RAF/RAS oncogenes and mismatch-repair status. Nature. 2002;418(6901):934.
121. Brandstedt J, Wangefjord S, Nodin B, Eberhard J, Sundstrom M, Manjer J, et al. Associations of anthropometric factors with KRAS and BRAF mutation status of primary colorectal cancer in men and women: a cohort study. PLoS One. 2014;9(2):2014.
122. Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, et al. High frequency of mutations of the PIK3CA gene in human cancers. Science. 2004;304(5670):11.
123. Lin PC, Lin JK, Lin HH, Lan YT, Lin CC, Yang SH, et al. A comprehensive analysis of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) loss in colorectal cancer. World J Surg Oncol. 2015;13(1):015-0601.
124. Yin Y, Shen WH. PTEN: a new guardian of the genome. Oncogene. 2008;27(41):5443-53.
125. Therkildsen C, Bergmann TK, Henrichsen-Schnack T, Ladelund S, Nilbert M. The predictive value of KRAS, NRAS, BRAF, PIK3CA and PTEN for anti-EGFR treatment in metastatic colorectal cancer: a systematic review and meta-analysis. Acta Oncol. 2014;53(7):852-64.
126. Alliot C. Relevance of EGFR expression in colorectal cancer. Ann Oncol. 2005;16(9):1557-8 (author reply 1558-9. Epub 2005 May 3; 2005).
127. Spano JP, Lagorce C, Atlan D, Milano G, Domont J, Benamouzig R, et al. Impact of EGFR expression on colorectal cancer patient prognosis and survival. Ann Oncol. 2005;16(1):102-8.
128. She QB, Solit DB, Ye Q, O'Reilly KE, Lobo J, Rosen N. The BAD protein integrates survival signaling by EGFR/MAPK and PI3 K/Akt kinase pathways in PTEN-deficient tumour cells. Cancer Cell. 2005;8(4):287-97.
129. Khandekar MJ, Cohen P, Spiegelman BM. Molecular mechanisms of cancer development in obesity. Nat Rev Cancer. 2011;11(12):886-95.
130. Cleary MP, Grossmann ME. Minireview: obesity and breast cancer: the estrogen connection. Endocrinology. 2009;150(6):2537-42.
131. Simpson ER. Aromatase: biologic relevance of tissue-specific expression. Semin Reprod Med. 2004;22(1):11-23.
132. Tchernof A, Mansour MF, Pelletier M, Boulet MM, Nadeau M, Luu-The V. Updated survey of the steroid-converting enzymes in human adipose tissues. J Steroid Biochem Mol Biol. 2015;147:56-69.
133. Pollak M. The insulin and insulin-like growth factor receptor family in neoplasia: an update. Nat Rev Cancer. 2012;12(3):159-69.
134. 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.
135. Schoen RE, Tangen CM, Kuller LH, Burke GL, Cushman M, Tracy RP, et al. Increased blood glucose and insulin, body size, and incident colorectal cancer. J Natl Cancer Inst. 1999;91(13):1147-54.
136. Giovannucci E. Insulin and colon cancer. Cancer Causes Control. 1995;6(2):164-79.
137. Volkova E, Robinson BA, Willis J, Currie MJ, Dachs GU. Marginal effects of glucose, insulin and insulin-like growth factor on chemotherapy response in endothelial and colorectal cancer cells. Oncol Lett. 2014;7(2):311-20.
138. Lahm H, Suardet L, Laurent PL, Fischer JR, Ceyhan A, Givel JC, et al. Growth regulation and co-stimulation of human colorectal cancer cell lines by insulin-like growth factor I, II and transforming growth factor alpha. Br J Cancer. 1992;65(3):341-6.
139. Tricoli JV, Rall LB, Karakousis CP, Herrera L, Petrelli NJ, Bell GI, et al. Enhanced levels of insulin-like growth factor messenger RNA in human colon carcinomas and liposarcomas. Cancer Res. 1986;46(12 Pt 1):6169-73.
140. Remacle-Bonnet MM, Garrouste FL, Heller S, Andre F, Marvaldi JL, Pommier GJ. Insulin-like growth factor-I protects colon cancer cells from death factor-induced apoptosis by potentiating tumour necrosis factor alpha-induced mitogen-activated protein kinase and nuclear factor kappaB signaling pathways. Cancer Res. 2000;60(7):2007-17.
141. Guo YS, Jin GF, Houston CW, Thompson JC, Townsend CM Jr. Insulin-like growth factor-I promotes multidrug resistance in MCLM colon cancer cells. J Cell Physiol. 1998;175(2):141-8.
142. Koenuma M, Yamori T, Tsuruo T. Insulin and insulin-like growth factor 1 stimulate proliferation of metastatic variants of colon carcinoma 26. Jpn J Cancer Res. 1989;80(1):51-8.
143. Bjorndahl M, Cao R, Nissen LJ, Clasper S, Johnson LA, Xue Y, et al. Insulin-like growth factors 1 and 2 induce lymphangiogenesis in vivo. Proc Natl Acad Sci USA. 2005;102(43):15593-8.
144. Sekharam M, Zhao H, Sun M, Fang Q, Zhang Q, Yuan Z, et al. Insulin-like growth factor 1 receptor enhances invasion and induces resistance to apoptosis of colon cancer cells through the Akt/Bcl-x(L) pathway. Cancer Res. 2003;63(22):7708-16.
145. Wu Y, Yakar S, Zhao L, Hennighausen L, LeRoith D. Circulating insulin-like growth factor-I levels regulate colon cancer growth and metastasis. Cancer Res. 2002;62(4):1030-5.
146. Comstock SS, Hortos K, Kovan B, McCaskey S, Pathak DR, Fenton JI. Adipokines and obesity are associated with colorectal polyps in adult males: a cross-sectional study. PLoS One. 2014;9(1):e85939.
147. Yamaji T, Iwasaki M, Sasazuki S, Tsugane S. Interaction between adiponectin and leptin influences the risk of colorectal adenoma. Cancer Res. 2010;70(13):5430-7.
148. Comstock SS, Lewis MM, Pathak DR, Hortos K, Kovan B, Fenton JI. Cross-sectional analysis of obesity and serum analytes in males identifies sRAGE as a novel biomarker inversely associated with diverticulosis. PLoS One. 2014;9(4):e95232.
149. Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science. 1995;269(5223):540-3.
150. Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science. 1995;269(5223):543-6.
151. Miyamoto S, Yasui Y, Tanaka T, Ohigashi H, Murakami A. Suppressive effects of nobiletin on hyperleptinemia and colitis-related colon carcinogenesis in male ICR mice. Carcinogenesis. 2008;29(5):1057-63.
152. Ogunwobi OO, Beales IL. Cyclo-oxygenase-independent inhibition of apoptosis and stimulation of proliferation by leptin in human colon cancer cells. Dig Dis Sci. 2007;52(8):1934-45.
153. Fenton JI, Lavigne JA, Perkins SN, Liu H, Chandramouli GV, Shih JH, et al. Microarray analysis reveals that leptin induces autocrine/paracrine cascades to promote survival and proliferation of colon epithelial cells in an Apc genotype-dependent fashion. Mol Carcinog. 2008;47(1):9-21.
154. Bergstrom A, Pisani P, Tenet V, Wolk A, Adami HO. Overweight as an avoidable cause of cancer in Europe. Int J Cancer. 2001;91(3):421-30.
155. Chia VM, Newcomb PA, Lampe JW, White E, Mandelson MT, McTiernan A, et al. Leptin concentrations, leptin receptor polymorphisms, and colorectal adenoma risk. Cancer Epidemiol Biomark Prev. 2007;16(12):2697-703.
156. Park J, Scherer PE. Adipocyte-derived endotrophin promotes malignant tumour progression. J Clin Invest. 2012;122(11):4243-56.
157. Park J, Scherer PE. Endotrophin in the tumour stroma: a new therapeutic target for breast cancer? Expert Rev Anticancer Ther. 2013;13(2):111-3. doi: 10.1586/era.12.164.
158. Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity. Annu Rev Immunol. 2011;29:415-45.
159. Yehuda-Shnaidman E, Schwartz B. Mechanisms linking obesity, inflammation and altered metabolism to colon carcinogenesis. Obes Rev. 2012;13(12):1083-95.
160. Hursting SD, Dunlap SM. Obesity, metabolic dysregulation, and cancer: a growing concern and an inflammatory (and microenvironmental) issue. Ann N Y Acad Sci. 2012;2012:82-7.
161. Vazzana N, Riondino S, Toto V, Guadagni F, Roselli M, Davi G, et al. Obesity-driven inflammation and colorectal cancer. Curr Med Chem. 2012;19(34):5837-53.
162. Gilbert CA, Slingerland JM. Cytokines, obesity, and cancer: new insights on mechanisms linking obesity to cancer risk and progression. Annu Rev Med. 2013;64:45-57.
163. Hwang WL, Yang MH, Tsai ML, Lan HY, Su SH, Chang SC, et al. SNAIL regulates interleukin-8 expression, stem cell-like activity, and tumourigenicity of human colorectal carcinoma cells. Gastroenterology. 2011;141(1):279-91.
164. Shah MS, Fogelman DR, Raghav KP, Heymach JV, Tran HT, Jiang ZQ, et al. Joint prognostic effect of obesity and chronic systemic inflammation in patients with metastatic colorectal cancer. Cancer. 2015;14:2968-75.
165. Taniguchi K, Karin M. IL-6 and related cytokines as the critical lynchpins between inflammation and cancer. Semin Immunol. 2014;26(1):54-74.
166. Lee EY, Lee ZH, Song YW. CXCL10 and autoimmune diseases. Autoimmun Rev. 2009;8(5):379-83.
167. O'Toole A, Michielsen AJ, Nolan B, Tosetto M, Sheahan K, Mulcahy HE, et al. Tumour microenvironment of both early- and late-stage colorectal cancer is equally immunosuppressive. Br J Cancer. 2014;111(5):927-32.
168. Park-Min KH, Antoniv TT, Ivashkiv LB. Regulation of macrophage phenotype by long-term exposure to IL-10. Immunobiology. 2005;210(2-4):77-86.
169. Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007;117(1):175-84.
170. Edin S, Wikberg ML, Dahlin AM, Rutegard J, Oberg A, Oldenborg PA, et al. The distribution of macrophages with a M1 or M2 phenotype in relation to prognosis and the molecular characteristics of colorectal cancer. PLoS One. 2012;7(10):15.
171. Wong SC, Puaux AL, Chittezhath M, Shalova I, Kajiji TS, Wang X, et al. Macrophage polarization to a unique phenotype driven by B cells. Eur J Immunol. 2010;40(8):2296-307.
172. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436-44.
173. Mantovani A. B cells and macrophages in cancer: yin and yang. Nat Med. 2011;17(3):285-6. doi: 10.1038/nm0311-285.
174. Galon J, Mlecnik B, Bindea G, Angell HK, Berger A, Lagorce C, et al. Towards the introduction of the 'Immunoscore' in the classification of malignant tumours. J Pathol. 2014;232(2):199-209.
175. Xiao Y, Freeman GJ. The microsatellite instable subset of colorectal cancer is a particularly good candidate for checkpoint blockade immunotherapy. Cancer Discov. 2015;5(1):16-8.
176. Prendergast GC, Smith C, Thomas S, Mandik-Nayak L, Laury-Kleintop L, Metz R, et al. Indoleamine 2,3-dioxygenase pathways of pathogenic inflammation and immune escape in cancer. Cancer Immunol Immunother. 2014;63(7):721-35.
177. Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, 1999-2004. JAMA. 2006;295(13):1549-55.
178. Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser. 1995;854:1-452.
179. Guiu B, Petit JM, Bonnetain F, Ladoire S, Guiu S, Cercueil JP, et al. Visceral fat area is an independent predictive biomarker of outcome after first-line bevacizumab-based treatment in metastatic colorectal cancer. Gut. 2010;59(3):341-7.
180. Romero-Corral A, Somers VK, Sierra-Johnson J, Thomas RJ, Collazo-Clavell ML, Korinek J, et al. Accuracy of body mass index in diagnosing obesity in the adult general population. Int J Obes. 2008;32(6):959-66.
181. Patel GS, Ullah S, Beeke C, Hakendorf P, Padbury R, Price TJ, et al. Association of BMI with overall survival in patients with mCRC who received chemotherapy versus EGFR and VEGF-targeted therapies. Cancer Med. 2015;4(10):1461-71.
182. Wu S, Liu J, Wang X, Li M, Gan Y, Tang Y. Association of obesity and overweight with overall survival in colorectal cancer patients: a meta-analysis of 29 studies. Cancer Causes Control. 2014;25(11):1489-502.
183. Fedirko V, Romieu I, Aleksandrova K, Pischon T, Trichopoulos D, Peeters PH, et al. Pre-diagnostic anthropometry and survival after colorectal cancer diagnosis in Western European populations. Int J Cancer. 2014;135(8):1949-60.
184. Slattery ML, Berry TD, Potter J, Caan B. Diet diversity, diet composition, and risk of colon cancer (United States). Cancer Causes Control. 1997;8(6):872-82.
185. Schulz MD, Atay C, Heringer J, Romrig FK, Schwitalla S, Aydin B, et al. High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity. Nature. 2014;514(7523):508-12.
186. Orlich MJ, Singh PN, Sabate J, Fan J, Sveen L, Bennett H, et al. Vegetarian dietary patterns and the risk of colorectal cancers. JAMA Intern Med. 2015;175(5):767-76.
187. Franco M, Bilal U, Ordunez P, Benet M, Morejon A, Caballero B et al. Population-wide weight loss and regain in relation to diabetes burden and cardiovascular mortality in Cuba 1980-2010: repeated cross sectional surveys and ecological comparison of secular trends. BMJ. 2013;2013(9).
188. Volkova E, Willis JA, Wells JE, Robinson BA, Dachs GU, Currie MJ. Association of angiopoietin-2, C-reactive protein and markers of obesity and insulin resistance with survival outcome in colorectal cancer. Br J Cancer. 2011;104(1):51-9.
189. Kostic AD, Gevers D, Pedamallu CS, Michaud M, Duke F, Earl AM, et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 2012;22(2):292-8.
190. Flanagan L, Schmid J, Ebert M, Soucek P, Kunicka T, Liska V, et al. Fusobacterium nucleatum associates with stages of colorectal neoplasia development, colorectal cancer and disease outcome. Eur J Clin Microbiol Infect Dis. 2014;33(8):1381-90.
191. Tahara T, Yamamoto E, Suzuki H, Maruyama R, Chung W, Garriga J, et al. Fusobacterium in colonic flora and molecular features of colorectal carcinoma. Cancer Res. 2014;74(5):1311-8.
192. Mima K, Nishihara R, Qian ZR, Cao Y, Sukawa Y, Nowak JA, et al. Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis. Gut. 2015;2015(26):2015-310101.
193. Mima K, Sukawa Y, Nishihara R, Qian ZR, Yamauchi M, Inamura K, et al. Fusobacterium nucleatum and T Cells in Colorectal Carcinoma. JAMA Oncol. 2015;1(5):653-61.
194. Lippitz BE. Cytokine patterns in patients with cancer: a systematic review. Lancet Oncol. 2013;14(6):e218-28.
195. Krzystek-Korpacka M, Diakowska D, Kapturkiewicz B, Bebenek M, Gamian A. Profiles of circulating inflammatory cytokines in colorectal cancer (CRC), high cancer risk conditions, and health are distinct. Possible implications for CRC screening and surveillance. Cancer Lett. 2013;337(1):107-14.
196. Di Caro G, Marchesi F, Galdiero MR, Grizzi F. Immune mediators as potential diagnostic tools for colorectal cancer: from experimental rationale to early clinical evidence. Expert Rev Mol Diagn. 2014;14(3):387-99.
197. Shah MS, Fogelman DR, Raghav KP, Heymach JV, Tran HT, Jiang ZQ, et al. Joint prognostic effect of obesity and chronic systemic inflammation in patients with metastatic colorectal cancer. Cancer. 2015;2015(14):29440.
198. Ho GY, Wang T, Gunter MJ, Strickler HD, Cushman M, Kaplan RC, et al. Adipokines linking obesity with colorectal cancer risk in postmenopausal women. Cancer Res. 2012;72(12):3029-37.
199. Ogino S, Chan AT, Fuchs CS, Giovannucci E. Molecular pathological epidemiology of colorectal neoplasia: an emerging transdisciplinary and interdisciplinary field. Gut. 2011;60(3):397-411.
200. Ogino S, Lochhead P, Chan AT, Nishihara R, Cho E, Wolpin BM, et al. Molecular pathological epidemiology of epigenetics: emerging integrative science to analyze environment, host, and disease. Mod Pathol. 2013;26(4):465-84.
201. 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.