Advertisement

Colorectal Cancer: Epidemiology, Disease Mechanisms and Interventions to Reduce Onset and Mortality

Published:February 12, 2016DOI:https://doi.org/10.1016/j.clcc.2016.02.008

      Abstract

      Colorectal cancer (CRC) is a multifactorial disease resulting from lifestyle, genetic, and environmental factors. There are hereditary and non-hereditary CRC types; however, the majority are non-hereditary and mainly caused by somatic mutations in response to environmental factors. In past years, researchers have focused their attention on the mechanisms behind these factors and the methods of improving disease prevention and treatment. Improving the awareness of the population with regard to the benefits of a healthy lifestyle, including a balanced diet associated with exercise, could globally reduce CRC risk. The present review aims to address the current knowledge on CRC, taking into consideration the common molecular alterations upon different environmental and non-environmental factors, current and promising treatment interventions, and how all these factors may interact to positively or negatively influence CRC risk.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Clinical Colorectal Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Levine J.S.
        • Ahnen D.J.
        Clinical practice. Adenomatous polyps of the colon.
        N Engl J Med. 2006; 355: 2551-2557
        • Vogelstein B.
        • Fearon E.R.
        • Hamilton S.R.
        • et al.
        Genetic alterations during colorectal-tumor development.
        N Engl J Med. 1988; 319: 525-532
        • Paschos K.A.
        • Canovas D.
        • Bird N.C.
        The role of cell adhesion molecules in the progression of colorectal cancer and the development of liver metastasis.
        Cell Signal. 2009; 21: 665-674
        • Ogino S.
        • Stampfer M.
        Lifestyle factors and microsatellite instability in colorectal cancer: the evolving field of molecular pathological epidemiology.
        J Natl Cancer Inst. 2010; 102: 365-367
        • Liao X.
        • Lochhead P.
        • Nishihara R.
        • et al.
        Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival.
        N Engl J Med. 2012; 367: 1596-1606
        • Ely S.
        Personalized medicine: individualized care of cancer patients.
        Transl Res. 2009; 154: 303-308
        • Ogino S.
        • Lochhead P.
        • Giovannucci E.
        • Meyerhardt J.A.
        • Fuchs C.S.
        • Chan A.T.
        Discovery of colorectal cancer PIK3CA mutation as potential predictive biomarker: power and promise of molecular pathological epidemiology.
        Oncogene. 2014; 33: 2949-2955
        • Ferlay J.
        • Soerjomataram I.
        • Dikshit R.
        • et al.
        Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012.
        Int J Cancer. 2015; 136: E359-E386
        • Bailey C.E.
        • Hu C.Y.
        • You Y.N.
        • et al.
        Increasing disparities in the age-related incidences of colon and rectal cancers in the United States, 1975-2010.
        JAMA Surg. 2015; 150: 17-22
        • Kohler B.A.
        • Ward E.
        • McCarthy B.J.
        • et al.
        Annual report to the nation on the status of cancer, 1975-2007, featuring tumors of the brain and other nervous system.
        J Natl Cancer Inst. 2011; 103: 714-736
        • Jemal A.
        • Thun M.J.
        • Ries L.A.
        • et al.
        Annual report to the nation on the status of cancer, 1975-2005, featuring trends in lung cancer, tobacco use, and tobacco control.
        J Natl Cancer Inst. 2008; 100: 1672-1694
        • La Vecchia C.
        • Bosetti C.
        • Lucchini F.
        • et al.
        Cancer mortality in Europe, 2000-2004, and an overview of trends since 1975.
        Ann Oncol. 2010; 21: 1323-1360
      1. INCA: Atlas de mortalidade por câncer. 2008 (Available at:) (Accessed: October 10, 2015)
        • Center M.M.
        • Jemal A.
        • Smith R.A.
        • Ward E.
        Worldwide variations in colorectal cancer.
        CA Cancer J Clin. 2009; 59: 366-378
        • Freedman A.N.
        • Slattery M.L.
        • Ballard-Barbash R.
        • et al.
        Colorectal cancer risk prediction tool for white men and women without known susceptibility.
        J Clin Oncol. 2009; 27: 686-693
        • Johns L.E.
        • Houlston R.S.
        A systematic review and meta-analysis of familial colorectal cancer risk.
        Am J Gastroenterol. 2001; 96: 2992-3003
        • Cottet V.
        • Pariente A.
        • Nalet B.
        • et al.
        Colonoscopic screening of first-degree relatives of patients with large adenomas: increased risk of colorectal tumors.
        Gastroenterology. 2007; 133: 1086-1092
        • Burt R.
        • Neklason D.W.
        Genetic testing for inherited colon cancer.
        Gastroenterology. 2005; 128: 1696-1716
        • Fearon E.R.
        Molecular genetics of colorectal cancer.
        Ann Rev Pathol. 2011; 6: 479-507
        • Steliarova-Foucher E.
        • O'Callaghan M.
        • Ferlay J.
        • et al.
        The European Cancer Observatory: a new data resource.
        Eur J Cancer. 2015; 51: 1131-1143
        • Froggatt N.J.
        • Green J.
        • Brassett C.
        • et al.
        A common MSH2 mutation in English and North American HNPCC families: origin, phenotypic expression, and sex specific differences in colorectal cancer.
        J Med Genet. 1999; 36: 97-102
        • Armaghany T.
        • Wilson J.D.
        • Chu Q.
        • Mills G.
        Genetic alterations in colorectal cancer.
        Gastrointest Cancer Res. 2012; 5: 19-27
        • Sarasqueta A.F.
        • Forte G.
        • Corver W.E.
        • et al.
        Integral analysis of p53 and its value as prognostic factor in sporadic colon cancer.
        BMC Cancer. 2013; 13: 277
        • Rajagopalan H.
        • Lengauer C.
        Aneuploidy and cancer.
        Nature. 2004; 432: 338-341
        • Smith G.
        • Carey F.A.
        • Beattie J.
        • et al.
        Mutations in APC, Kirsten-ras, and p53–alternative genetic pathways to colorectal cancer.
        Proc Natl Acad Sci U S A. 2002; 99: 9433-9438
        • Fodde R.
        • Kuipers J.
        • Rosenberg C.
        • et al.
        Mutations in the APC tumour suppressor gene cause chromosomal instability.
        Nat Cell Biol. 2001; 3: 433-438
        • de la Chapelle A.
        • Hampel H.
        Clinical relevance of microsatellite instability in colorectal cancer.
        J Clin Oncol. 2010; 28: 3380-3387
        • Boland C.R.
        • Goel A.
        Microsatellite instability in colorectal cancer.
        Gastroenterology. 2010; 138: 2073-2087.e3
        • Toyota M.
        • Ahuja N.
        • Ohe-Toyota M.
        • Herman J.G.
        • Baylin S.B.
        • Issa J.P.
        CpG island methylator phenotype in colorectal cancer.
        Proc Natl Acad Sci U S A. 1999; 96: 8681-8686
        • Nazemalhosseini Mojarad E.
        • Kuppen P.J.
        • Aghdaei H.A.
        • Zali M.R.
        The CpG island methylator phenotype (CIMP) in colorectal cancer.
        Gastroenterol Hepatol Bed Bench. 2013; 6: 120-128
        • Lao V.V.
        • Grady W.M.
        Epigenetics and colorectal cancer.
        Nat Rev Gastroenterol Hepatol. 2011; 8: 686-700
        • Geiersbach K.B.
        • Samowitz W.S.
        Microsatellite instability and colorectal cancer.
        Arch Pathol Lab Med. 2011; 135: 1269-1277
        • Jass J.R.
        • Smith M.
        Sialic acid and epithelial differentiation in colorectal polyps and cancer–a morphological, mucin and lectin histochemical study.
        Pathology. 1992; 24: 233-242
        • Laiho P.
        • Kokko A.
        • Vanharanta S.
        • et al.
        Serrated carcinomas form a subclass of colorectal cancer with distinct molecular basis.
        Oncogene. 2007; 26: 312-320
        • Yamane L.
        • Scapulatempo-Neto C.
        • Reis R.M.
        • Guimaraes D.P.
        Serrated pathway in colorectal carcinogenesis.
        World J Gastroenterol. 2014; 20: 2634-2640
        • Koinuma K.
        • Shitoh K.
        • Miyakura Y.
        • et al.
        Mutations of BRAF are associated with extensive hMLH1 promoter methylation in sporadic colorectal carcinomas.
        Int J Cancer. 2004; 108: 237-242
        • Leggett B.
        • Whitehall V.
        Role of the serrated pathway in colorectal cancer pathogenesis.
        Gastroenterology. 2010; 138: 2088-2100
        • Rustgi A.K.
        BRAF: a driver of the serrated pathway in colon cancer.
        Cancer Cell. 2013; 24: 1-2
        • Lubomierski N.
        • Plotz G.
        • Wormek M.
        • et al.
        BRAF mutations in colorectal carcinoma suggest two entities of microsatellite-unstable tumors.
        Cancer. 2005; 104: 952-961
        • Moran A.
        • Ortega P.
        • de Juan C.
        • et al.
        Differential colorectal carcinogenesis: molecular basis and clinical relevance.
        World J Gastrointest Oncol. 2010; 2: 151-158
        • Qiu L.X.
        • Mao C.
        • Zhang J.
        • et al.
        Predictive and prognostic value of KRAS mutations in metastatic colorectal cancer patients treated with cetuximab: a meta-analysis of 22 studies.
        Eur J Cancer. 2010; 46: 2781-2787
        • Gil Ferreira C.
        • Aran V.
        • Zalcberg-Renault I.
        • et al.
        KRAS mutations: variable incidences in a Brazilian cohort of 8,234 metastatic colorectal cancer patients.
        BMC Gastroenterol. 2014; 14: 73
        • Stefanius K.
        • Ylitalo L.
        • Tuomisto A.
        • et al.
        Frequent mutations of KRAS in addition to BRAF in colorectal serrated adenocarcinoma.
        Histopathology. 2011; 58: 679-692
        • O'Brien M.J.
        • Yang S.
        • Mack C.
        • et al.
        Comparison of microsatellite instability, CpG island methylation phenotype, BRAF and KRAS status in serrated polyps and traditional adenomas indicates separate pathways to distinct colorectal carcinoma end points.
        Am J Surg Pathol. 2006; 30: 1491-1501
        • Irahara N.
        • Baba Y.
        • Nosho K.
        • et al.
        NRAS mutations are rare in colorectal cancer.
        Diagn Mol Pathol. 2010; 19: 157-163
        • Orlich M.J.
        • Singh P.N.
        • Sabate J.
        • et al.
        Vegetarian dietary patterns and the risk of colorectal cancers.
        JAMA Intern Med. 2015; 175: 767-776
        • Key T.J.
        • Appleby P.N.
        • Crowe F.L.
        • Bradbury K.E.
        • Schmidt J.A.
        • Travis R.C.
        Cancer in British vegetarians: updated analyses of 4998 incident cancers in a cohort of 32,491 meat eaters, 8612 fish eaters, 18,298 vegetarians, and 2246 vegans.
        Am J Clin Nutr. 2014; 100: 378S-385S
        • Lee C.G.
        • Hahn S.J.
        • Song M.K.
        • et al.
        Vegetarianism as a protective factor for colorectal adenoma and advanced adenoma in Asians.
        Dig Dis Sci. 2014; 59: 1025-1035
        • Tantamango-Bartley Y.
        • Jaceldo-Siegl K.
        • Fan J.
        • Fraser G.
        Vegetarian diets and the incidence of cancer in a low-risk population.
        Cancer Epidemiol Biomarkers Prev. 2013; 22: 286-294
        • Zhu B.
        • Sun Y.
        • Qi L.
        • Zhong R.
        • Miao X.
        Dietary legume consumption reduces risk of colorectal cancer: evidence from a meta-analysis of cohort studies.
        Sci Rep. 2015; 5: 8797
        • Gonzalez C.A.
        • Riboli E.
        Diet and cancer prevention: contributions from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.
        Eur J Cancer. 2010; 46: 2555-2562
        • Aune D.
        • Chan D.S.
        • Lau R.
        • et al.
        Dietary fibre, whole grains, and risk of colorectal cancer: systematic review and dose-response meta-analysis of prospective studies.
        BMJ. 2011; 343: d6617
        • Alexander D.D.
        • Miller A.J.
        • Cushing C.A.
        • Lowe K.A.
        Processed meat and colorectal cancer: a quantitative review of prospective epidemiologic studies.
        Eur J Cancer Prev. 2010; 19: 328-341
        • Cross A.J.
        • Ferrucci L.M.
        • Risch A.
        • et al.
        A large prospective study of meat consumption and colorectal cancer risk: an investigation of potential mechanisms underlying this association.
        Cancer Res. 2010; 70: 2406-2414
        • Raskov H.
        • Pommergaard H.C.
        • Burcharth J.
        • Rosenberg J.
        Colorectal carcinogenesis–update and perspectives.
        World J Gastroenterol. 2014; 20: 18151-18164
        • Shiels M.S.
        • Katki H.A.
        • Freedman N.D.
        • et al.
        Cigarette smoking and variations in systemic immune and inflammation markers.
        J Natl Cancer Inst. 2014; 106
        • Derry M.M.
        • Raina K.
        • Agarwal C.
        • Agarwal R.
        Identifying molecular targets of lifestyle modifications in colon cancer prevention.
        Front Oncol. 2013; 3: 119
        • US Department of Health and Human Services
        The health consequences of smoking—50 years of progress: A Report of the Surgeon General.
        U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, Atlanta2014
        • Botteri E.
        • Iodice S.
        • Bagnardi V.
        • Raimondi S.
        • Lowenfels A.B.
        • Maisonneuve P.
        Smoking and colorectal cancer: a meta-analysis.
        JAMA. 2008; 300: 2765-2778
        • Botteri E.
        • Iodice S.
        • Raimondi S.
        • Maisonneuve P.
        • Lowenfels A.B.
        Cigarette smoking and adenomatous polyps: a meta-analysis.
        Gastroenterology. 2008; 134: 388-395
        • Jensen K.
        • Afroze S.
        • Munshi M.K.
        • Guerrier M.
        • Glaser S.S.
        Mechanisms for nicotine in the development and progression of gastrointestinal cancers.
        Transl Gastrointest Cancer. 2012; 1: 81-87
        • Zhu Y.
        • Yang S.R.
        • Wang P.P.
        • et al.
        Influence of pre-diagnostic cigarette smoking on colorectal cancer survival: overall and by tumour molecular phenotype.
        Br J Cancer. 2014; 110: 1359-1366
        • Liang P.S.
        • Chen T.Y.
        • Giovannucci E.
        Cigarette smoking and colorectal cancer incidence and mortality: systematic review and meta-analysis.
        Int J Cancer. 2009; 124: 2406-2415
        • Yang B.
        • Jacobs E.J.
        • Gapstur S.M.
        • Stevens V.
        • Campbell P.T.
        Active smoking and mortality among colorectal cancer survivors: the Cancer Prevention Study II Nutrition Cohort.
        J Clin Oncol. 2015; 33: 885-893
        • Fedewa S.A.
        • Sauer A.G.
        • Siegel R.L.
        • Jemal A.
        Prevalence of major risk factors and use of screening tests for cancer in the United States.
        Cancer Epidemiol Biomarkers Prev. 2015; 24: 637-652
        • Walter V.
        • Jansen L.
        • Hoffmeister M.
        • Ulrich A.
        • Chang-Claude J.
        • Brenner H.
        Smoking and survival of colorectal cancer patients: population-based study from Germany.
        Int J Cancer. 2015; 137: 1433-1445
        • Chen K.
        • Xia G.
        • Zhang C.
        • Sun Y.
        Correlation between smoking history and molecular pathways in sporadic colorectal cancer: a meta-analysis.
        Int J Clin Exp Med. 2015; 8: 3241-3257
        • Huxley R.R.
        • Ansary-Moghaddam A.
        • Clifton P.
        • Czernichow S.
        • Parr C.L.
        • Woodward M.
        The impact of dietary and lifestyle risk factors on risk of colorectal cancer: a quantitative overview of the epidemiological evidence.
        Int J Cancer. 2009; 125: 171-180
        • Rueda M.
        • Robertson Y.
        • Acott A.
        • et al.
        Association of tobacco and alcohol use with earlier development of colorectal pathology: should screening guidelines be modified to include these risk factors?.
        Am J Surg. 2012; 204 (discussion: 967-8): 963-967
        • Bardou M.
        • Montembault S.
        • Giraud V.
        • et al.
        Excessive alcohol consumption favours high risk polyp or colorectal cancer occurrence among patients with adenomas: a case control study.
        Gut. 2002; 50: 38-42
        • Boffetta P.
        • Hashibe M.
        Alcohol and cancer.
        Lancet Oncol. 2006; 7: 149-156
        • Seitz H.K.
        • Becker P.
        Alcohol metabolism and cancer risk.
        Alcohol Res Health. 2007; 30 (44-7): 38-41
        • Heit C.
        • Dong H.
        • Chen Y.
        • Shah Y.M.
        • Thompson D.C.
        • Vasiliou V.
        Transgenic mouse models for alcohol metabolism, toxicity, and cancer.
        Adv Exp Med Biol. 2015; 815: 375-387
        • Park Y.
        • Freedman A.N.
        • Gail M.H.
        • et al.
        Validation of a colorectal cancer risk prediction model among white patients age 50 years and older.
        J Clin Oncol. 2009; 27: 694-698
        • Steffen A.
        • MacInnis R.J.
        • Joshy G.
        • Giles G.G.
        • Banks E.
        • Roder D.
        Development and validation of a risk score predicting risk of colorectal cancer.
        Cancer Epidemiol Biomarkers Prev. 2014; 23: 2543-2552
        • Isella C.
        • Terrasi A.
        • Bellomo S.E.
        • et al.
        Stromal contribution to the colorectal cancer transcriptome.
        Nat Genet. 2015; 47: 312-319
        • Calon A.
        • Lonardo E.
        • Berenguer-Llergo A.
        • et al.
        Stromal gene expression defines poor-prognosis subtypes in colorectal cancer.
        Nat Genet. 2015; 47: 320-329
        • Aalok Kumar H.F.K.
        • Lim H.J.
        • Renouf D.J.
        • Woods R.
        • Speers C.
        • Cheung W.Y.
        • British Columbia Cancer Agency, Vancouver, BC, Canada
        Adjuvant chemotherapy (AC) use and outcomes in stage II colon cancer (CC) with and without poor prognostic features. 2012 ASCO Annual Meeting.
        J Clin Oncol. 2012; 30 (Abstract 3527)
        • Gray R.
        • Barnwell J.
        • McConkey C.
        • Hills R.K.
        • Williams N.S.
        • Kerr D.J.
        Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study.
        Lancet. 2007; 370: 2020-2029
        • Andre T.
        • Boni C.
        • Navarro M.
        • et al.
        Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial.
        J Clin Oncol. 2009; 27: 3109-3116
        • Tournigand C.
        • Andre T.
        • Bonnetain F.
        • et al.
        Adjuvant therapy with fluorouracil and oxaliplatin in stage II and elderly patients (between ages 70 and 75 years) with colon cancer: subgroup analyses of the Multicenter International Study of Oxaliplatin, Fluorouracil, and Leucovorin in the Adjuvant Treatment of Colon Cancer trial.
        J Clin Oncol. 2012; 30: 3353-3360
        • Sargent D.J.
        • Goldberg R.M.
        • Jacobson S.D.
        • et al.
        A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients.
        N Engl J Med. 2001; 345: 1091-1097
        • Sargent D.J.
        • Yothers G.
        • Tejpar S.
        • et al.
        • ACCENT Collaborative Group; Mayo Clinic, Rochester, MN; National Surgical Adjuvant Breast and Bowel Project Biostatistical Center, and University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA; University of Leuven, KUL, Leuven, Belgium; Brigham and Women's Hospital, Boston, MA; Mayo Clinic College of Medicine, Rochester, MN; Pitie-Salpetriere Hospital, Paris, France; Oncology Department, Ospedali Riuniti di Bergamo, Bergamo, Italy; Mount Sinai Hospital, Toronto, ON, Canada; The University of Texas MD Anderson Cancer Center, Houston, TX; Institut Paoli-Calmettes, Marseille, France; NSABP, Pittsburgh, PA; NSABP, and Severance Biomedical Science Institute and Department of Medical Oncology, Yonsei University College of Medicine, Pittsburgh, PA; Swiss Group for Clinical Cancer Research, Bern, Switzerland; University Hospital Geneva, Geneva, Switzerland; Mayo Clinic, Jacksonville, FL
        Prognostic impact of deficient mismatch repair (dMMR) in 7,803 stage II/III colon cancer (CC) patients (pts): a pooled individual pt data analysis of 17 adjuvant trials in the ACCENT database.
        J Clin Oncol. 2014; 32 (Abstract 3507): 5
        • Alberts S.R.
        • Sargent D.J.
        • Nair S.
        • et al.
        Effect of oxaliplatin, fluorouracil, and leucovorin with or without cetuximab on survival among patients with resected stage III colon cancer: a randomized trial.
        JAMA. 2012; 307: 1383-1393
        • Winer E.
        • Gralow J.
        • Diller L.
        • et al.
        Clinical cancer advances 2008: major research advances in cancer treatment, prevention, and screening–a report from the American Society of Clinical Oncology.
        J Clin Oncol. 2009; 27: 812-826
        • Karapetis C.S.
        • Khambata-Ford S.
        • Jonker D.J.
        • et al.
        K-ras mutations and benefit from cetuximab in advanced colorectal cancer.
        N Engl J Med. 2008; 359: 1757-1765
        • Benvenuti S.
        • Sartore-Bianchi A.
        • Di Nicolantonio F.
        • et al.
        Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies.
        Cancer Res. 2007; 67: 2643-2648
        • Van Cutsem E.
        • Kohne C.H.
        • Hitre E.
        • et al.
        Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer.
        N Engl J Med. 2009; 360: 1408-1417
        • De Roock W.
        • Claes B.
        • Bernasconi D.
        • et al.
        Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis.
        Lancet Oncol. 2010; 11: 753-762
        • Siena S.
        • Sartore-Bianchi A.
        • Di Nicolantonio F.
        • Balfour J.
        • Bardelli A.
        Biomarkers predicting clinical outcome of epidermal growth factor receptor-targeted therapy in metastatic colorectal cancer.
        J Natl Cancer Inst. 2009; 101: 1308-1324
        • Bokemeyer C.
        • Bondarenko I.
        • Makhson A.
        • et al.
        Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer.
        J Clin Oncol. 2009; 27: 663-671
        • Amado R.G.
        • Wolf M.
        • Peeters M.
        • et al.
        Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer.
        J Clin Oncol. 2008; 26: 1626-1634
        • Siddiqui A.D.
        • Piperdi B.
        KRAS mutation in colon cancer: a marker of resistance to EGFR-I therapy.
        Ann Surg Oncol. 2010; 17: 1168-1176
        • Allegra C.J.
        • Jessup J.M.
        • Somerfield M.R.
        • et al.
        American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy.
        J Clin Oncol. 2009; 27: 2091-2096
        • Winder T.
        • Mundlein A.
        • Rhomberg S.
        • et al.
        Different types of K-Ras mutations are conversely associated with overall survival in patients with colorectal cancer.
        Oncol Rep. 2009; 21: 1283-1287
        • Al-Mulla F.
        • Milner-White E.J.
        • Going J.J.
        • Birnie G.D.
        Structural differences between valine-12 and aspartate-12 Ras proteins may modify carcinoma aggression.
        J Pathol. 1999; 187: 433-438
        • Andreyev H.J.
        • Norman A.R.
        • Cunningham D.
        • et al.
        Kirsten ras mutations in patients with colorectal cancer: the ‘RASCAL II’ study.
        Br J Cancer. 2001; 85: 692-696
        • Andreyev H.J.
        • Norman A.R.
        • Cunningham D.
        • Oates J.R.
        • Clarke P.A.
        Kirsten ras mutations in patients with colorectal cancer: the multicenter “RASCAL” study.
        J Natl Cancer Inst. 1998; 90: 675-684
        • Messner I.
        • Cadeddu G.
        • Huckenbeck W.
        • et al.
        KRAS p.G13D mutations are associated with sensitivity to anti-EGFR antibody treatment in colorectal cancer cell lines.
        J Cancer Res Clin Oncol. 2013; 139: 201-209
        • Kumar S.S.
        • Price T.J.
        • Mohyieldin O.
        • Borg M.
        • Townsend A.
        • Hardingham J.E.
        KRAS G13D mutation and sensitivity to cetuximab or panitumumab in a colorectal cancer cell line model.
        Gastrointest Cancer Res. 2014; 7: 23-26
        • Ciardiello F.
        • Kohne C.
        • Lenz H.
        • et al.
        Treatment outcome according to tumor RAS mutation status in CRYSTAL study patients with metastatic colorectal cancer (mCRC) randomized to FOLFIRI with/without cetuximab.
        J Clin Oncol. 2014; 32 (Abstract 3506): 5s
        • Maughan T.S.
        • Adams R.A.
        • Smith C.G.
        • et al.
        Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial.
        Lancet. 2011; 377: 2103-2114
        • Tveit K.M.
        • Guren T.
        • Glimelius B.
        • et al.
        Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer: the NORDIC-VII study.
        J Clin Oncol. 2012; 30: 1755-1762
        • Douillard J.Y.
        • Oliner K.S.
        • Siena S.
        • et al.
        Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer.
        N Engl J Med. 2013; 369: 1023-1034
        • Peeters M.
        • Price T.J.
        • Cervantes A.
        • et al.
        Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer.
        J Clin Oncol. 2010; 28: 4706-4713
        • Fuchs C.S.
        • Marshall J.
        • Mitchell E.
        • et al.
        Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study.
        J Clin Oncol. 2007; 25: 4779-4786
        • Giantonio B.J.
        • Catalano P.J.
        • Meropol N.J.
        • et al.
        Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200.
        J Clin Oncol. 2007; 25: 1539-1544
        • Van Cutsem E.
        • Tabernero J.
        • Lakomy R.
        • et al.
        Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen.
        J Clin Oncol. 2012; 30: 3499-3506
        • Venook A.P.
        • Lenz H.J.
        • Innocenti F.
        • et al.
        • Cancer and Leukemia Group B (Alliance), SWOG, and ECOG; University of California, San Francisco, San Francisco, CA; Duke University, Durham, NC; USC Norris Comprehensive Cancer Center, Los Angeles, CA; The University of North Carolina at Chapel Hill, Chapel Hill, NC; Mayo Clinic, Rochester, MN; Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN; Virginia Commonwealth University, Richmond, VA; Pritzker School of Medicine, The University of Chicago, Chicago, IL; Department of Medical Oncology, Yale University School of Medicine, New Haven, CT; Southeast Cancer Control Consortium, CCOP, Goldsboro, NC; The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH; Dana-Farber Cancer Institute, Boston, MA; American Society of Clinical Oncology, Alexandria, VA; Brigham and Women's Hospital, Boston, MA; SWOG and Oregon Health & Science University, Portland, OR
        CALGB/SWOG 80405: phase III trial of irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab (BV) or cetuximab (CET) for patients (pts) with KRAS wild-type (wt) untreated metastatic adenocarcinoma of the colon or rectum (MCRC); 2014 ASCO Annual Meeting.
        J Clin Oncol. 2014; 32 (Abstract LBA3): 5s
        • Grothey A.
        • Van Cutsem E.
        • Sobrero A.
        • et al.
        Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial.
        Lancet. 2013; 381: 303-312
        • Oikonomou E.
        • Koustas E.
        • Goulielmaki M.
        • Pintzas A.
        BRAF vs RAS oncogenes: are mutations of the same pathway equal? Differential signalling and therapeutic implications.
        Oncotarget. 2014; 5: 11752-11777
        • Xu Q.
        • Xu A.T.
        • Zhu M.M.
        • Tong J.L.
        • Xu X.T.
        • Ran Z.H.
        Predictive and prognostic roles of BRAF mutation in patients with metastatic colorectal cancer treated with anti-epidermal growth factor receptor monoclonal antibodies: a meta-analysis.
        J Dig Dis. 2013; 14: 409-416
        • Kushi L.H.
        • Doyle C.
        • McCullough M.
        • et al.
        American Cancer Society Guidelines on nutrition and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity.
        CA Cancer J Clin. 2012; 62: 30-67
        • Larsson S.C.
        • Wolk A.
        Obesity and colon and rectal cancer risk: a meta-analysis of prospective studies.
        Am J Clin Nutr. 2007; 86: 556-565
        • Danaei G.
        • Vander Hoorn S.
        • Lopez A.D.
        • Murray C.J.
        • Ezzati M.
        Causes of cancer in the world: comparative risk assessment of nine behavioural and environmental risk factors.
        Lancet. 2005; 366: 1784-1793
        • Calistri D.
        • Rengucci C.
        • Casadei Gardini A.
        • et al.
        Fecal DNA for noninvasive diagnosis of colorectal cancer in immunochemical fecal occult blood test-positive individuals.
        Cancer Epidemiol Biomarkers Prev. 2010; 19: 2647-2654
        • Goldstein D.A.
        • Shaib W.L.
        • Flowers C.R.
        Costs and effectiveness of genomic testing in the management of colorectal cancer.
        Oncology (Williston Park). 2015; 29: 175-183
        • Song B.P.
        • Jain S.
        • Lin S.Y.
        • et al.
        Detection of hypermethylated vimentin in urine of patients with colorectal cancer.
        J Mol Diagn. 2012; 14: 112-119
        • Mullard A.
        Alnylam dealt blow.
        Nat Biotechnol. 2009; 27: 213
        • Klabunde C.N.
        • Cronin K.A.
        • Breen N.
        • Waldron W.R.
        • Ambs A.H.
        • Nadel M.R.
        Trends in colorectal cancer test use among vulnerable populations in the United States.
        Cancer Epidemiol Biomarkers Prev. 2011; 20: 1611-1621
        • Zauber A.G.
        The impact of screening on colorectal cancer mortality and incidence: has it really made a difference?.
        Dig Dis Sci. 2015; 60: 681-691
        • Saito H.
        Colorectal cancer screening using immunochemical faecal occult blood testing in Japan.
        J Med Screen. 2006; 13: S6-S7
        • Shin H.R.
        • Masuyer E.
        • Ferlay J.
        • Curado M.P.
        Cancer in Asia - Incidence rates based on data in cancer incidence in five continents IX (1998-2002).
        Asian Pac J Cancer Prev. 2010; 11: 11-16