© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 11, 916-932,
June 2, 1999
© 1999 Oxford University Press
REVIEW |
Colorectal Cancer: Molecules and Populations
Correspondence to: John D. Potter, M.D., Ph.D., Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N. MP702, P.O. Box 19024, Seattle, WA 98109-1024 (e-mail: jpotter{at}fhcrc.org).
The epidemiology and molecular biology of colorectal cancer are reviewed with a view to understanding their interrelationship. Risk factors for colorectal neoplasia include a positive family history, meat consumption, smoking, and alcohol consumption. Important inverse associations exist with vegetables, nonsteroidal anti-inflammatory drugs (NSAIDs), hormone replacement therapy, and physical activity. There are several molecular pathways to colorectal cancer, especially the APC (adenomatous polyposis coli)-ß-catenin-Tcf (T-cell factor; a transcriptional activator) pathway and the pathway involving abnormalities of DNA mismatch repair. These are important, both in inherited syndromes (familial adenomatous polyposis [FAP] and hereditary nonpolyposis colorectal cancer [HNPCC], respectively) and in sporadic cancers. Other less well defined pathways exist. Expression of key genes in any of these pathways may be lost by inherited or acquired mutation or by hypermethylation. The roles of several of the environmental exposures in the molecular pathways either are established (e.g., inhibition of cyclooxygenase-2 by NSAIDs) or are suggested (e.g., meat and tobacco smoke as sources of specific blood-borne carcinogens; vegetables as a source of folate, antioxidants, and inducers of detoxifying enzymes). The roles of other factors (e.g., physical activity) remain obscure even when the epidemiology is quite consistent. There is also evidence that some metabolic pathways, e.g., those involving folate and heterocyclic amines, may be modified by polymorphisms in relevant genes, e.g., MTHFR (methylenetetrahydrofolate reductase) and NAT1 (N-acetyltransferase 1) and NAT2. There is at least some evidence that the general host metabolic state can provide a milieu that enhances or reduces the likelihood of cancer progression. Understanding the roles of environmental exposures and host susceptibilities in molecular pathways has implications for screening, treatment, surveillance, and prevention.
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K. G. Hauret, R. M. Bostick, C. E. Matthews, J. R. Hussey, M. F. Fina, K. R. Geisinger, and W. M. Roufail Physical Activity and Reduced Risk of Incident Sporadic Colorectal Adenomas: Observational Support for Mechanisms Involving Energy Balance and Inflammation Modulation Am. J. Epidemiol., May 15, 2004; 159(10): 983 - 992. [Abstract] [Full Text] [PDF]
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Y. Hirose, K. Hata, T. Kuno, K. Yoshida, K. Sakata, Y. Yamada, T. Tanaka, B. S. Reddy, and H. Mori Enhancement of development of azoxymethane-induced colonic premalignant lesions in C57BL/KsJ-db/db mice Carcinogenesis, May 1, 2004; 25(5): 821 - 825. [Abstract] [Full Text] [PDF]
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J. L. Bermejo, F. L. Buchner, and K. Hemminki Familial risk of endometrial cancer after exclusion of families that fulfilled Amsterdam, Japanese or Bethesda criteria for HNPCC Ann. Onc., April 1, 2004; 15(4): 598 - 604. [Abstract] [Full Text] [PDF]
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F.-F. Chu, R. S. Esworthy, P. G. Chu, J. A. Longmate, M. M. Huycke, S. Wilczynski, and J. H. Doroshow Bacteria-Induced Intestinal Cancer in Mice with Disrupted Gpx1 and Gpx2 Genes Cancer Res., February 1, 2004; 64(3): 962 - 968. [Abstract] [Full Text] [PDF]
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M Ponz de Leon, P Benatti, F Borghi, M Pedroni, A Scarselli, C Di Gregorio, L Losi, A Viel, M Genuardi, G Abbati, et al. Aetiology of colorectal cancer and relevance of monogenic inheritance Gut, January 1, 2004; 53(1): 115 - 122. [Abstract] [Full Text] [PDF]
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R. C. Lewis, R. M. Bostick, D. Xie, Z. Deng, M. J. Wargovich, M. F. Fina, W. M. Roufail, and K. R. Geisinger Polymorphism of the Cyclin D1 Gene, CCND1, and Risk for Incident Sporadic Colorectal Adenomas Cancer Res., December 1, 2003; 63(23): 8549 - 8553. [Abstract] [Full Text] [PDF]
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J. Satia-Abouta, J. A. Galanko, J. D. Potter, A. Ammerman, C. F. Martin, and R. S. Sandler Associations of Total Energy and Macronutrients with Colon Cancer Risk in African Americans and Whites: Results from the North Carolina Colon Cancer Study Am. J. Epidemiol., November 15, 2003; 158(10): 951 - 962. [Abstract] [Full Text] [PDF]
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A. H. Conney Enzyme Induction and Dietary Chemicals as Approaches to Cancer Chemoprevention: The Seventh DeWitt S. Goodman Lecture Cancer Res., November 1, 2003; 63(21): 7005 - 7031. [Abstract] [Full Text] [PDF]
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 K Pham, T Milovanovic, R J Barr, T Truong, and R F Holcombe Wnt ligand expression in malignant melanoma: pilot study indicating correlation with histopathological features Mol. Pathol., October 1, 2003; 56(5): 280 - 285. [Abstract] [Full Text] [PDF]
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 H. K. Weir, M. J. Thun, B. F. Hankey, L. A. G. Ries, H. L. Howe, P. A. Wingo, A. Jemal, E. Ward, R. N. Anderson, and B. K. Edwards Annual Report to the Nation on the Status of Cancer, 1975-2000, Featuring the Uses of Surveillance Data for Cancer Prevention and Control J Natl Cancer Inst, September 3, 2003; 95(17): 1276 - 1299. [Abstract] [Full Text] [PDF]
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E. Riboli and T. Norat Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk Am. J. Clinical Nutrition, September 1, 2003; 78(3): 559S - 569. [Abstract] [Full Text] [PDF]
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N. M. Probst-Hensch, H. Wang, V. H. H. Goh, A. Seow, H.-P. Lee, and M. C. Yu Determinants of Circulating Insulin-like Growth Factor I and Insulin-like Growth Factor Binding Protein 3 Concentrations in a Cohort of Singapore Men and Women Cancer Epidemiol. Biomarkers Prev., August 1, 2003; 12(8): 739 - 746. [Abstract] [Full Text] [PDF]
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J. Satia-Abouta, J. A. Galanko, C. F. Martin, J. D. Potter, A. Ammerman, and R. S. Sandler Associations of Micronutrients with Colon Cancer Risk in African Americans and Whites: Results from the North Carolina Colon Cancer Study Cancer Epidemiol. Biomarkers Prev., August 1, 2003; 12(8): 747 - 754. [Abstract] [Full Text] [PDF]
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K. Hemminki and X. Li Level of Education and the Risk of Cancer in Sweden Cancer Epidemiol. Biomarkers Prev., August 1, 2003; 12(8): 796 - 802. [Abstract] [Full Text] [PDF]
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S. M. Boyapati, R. M. Bostick, K. A. McGlynn, M. F. Fina, W. M. Roufail, K. R. Geisinger, M. Wargovich, A. Coker, and J. R. Hebert Calcium, Vitamin D, and Risk for Colorectal Adenoma: Dependency on Vitamin D Receptor BsmI Polymorphism and Nonsteroidal Anti-Inflammatory Drug Use? Cancer Epidemiol. Biomarkers Prev., July 1, 2003; 12(7): 631 - 637. [Abstract] [Full Text] [PDF]
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A. Miles, J. Wardle, K. McCaffery, S. Williamson, and W. Atkin The Effects of Colorectal Cancer Screening on Health Attitudes and Practices Cancer Epidemiol. Biomarkers Prev., July 1, 2003; 12(7): 651 - 655. [Full Text] [PDF]
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M. van Engeland, M. P. Weijenberg, G. M. J. M. Roemen, M. Brink, A. P. de Bruine, R. A. Goldbohm, P. A. van den Brandt, S. B. Baylin, A. F. P. M. de Goeij, and J. G. Herman Effects of Dietary Folate and Alcohol Intake on Promoter Methylation in Sporadic Colorectal Cancer: The Netherlands Cohort Study on Diet and Cancer Cancer Res., June 15, 2003; 63(12): 3133 - 3137. [Abstract] [Full Text] [PDF]
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R Scheenstra, F E M Rijcken, J J Koornstra, H Hollema, R Fodde, F H Menko, R H Sijmons, C M A Bijleveld, and J H Kleibeuker Rapidly progressive adenomatous polyposis in a patient with germline mutations in both the APC and MLH1 genes: the worst of two worlds Gut, June 1, 2003; 52(6): 898 - 899. [Abstract] [Full Text]
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E. W. Tiemersma, P. A. Wark, M. C. Ocke, A. Bunschoten, M. H. Otten, F. J. Kok, and E. Kampman Alcohol Consumption, Alcohol Dehydrogenase 3 Polymorphism, and Colorectal Adenomas Cancer Epidemiol. Biomarkers Prev., May 1, 2003; 12(5): 419 - 425. [Abstract] [Full Text] [PDF]
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 M. Hashimoto, Y. He, and E. S. Yeung On-line integration of PCR and cycle sequencing in capillaries: from human genomic DNA directly to called bases Nucleic Acids Res., April 15, 2003; 31(8): e41 - e41. [Abstract] [Full Text] [PDF]
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M. Brink, A. F.P.M. de Goeij, M. P. Weijenberg, G. M.J.M. Roemen, M. H.F.M. Lentjes, M. M.M. Pachen, K. M. Smits, A. P. de Bruine, R. A. Goldbohm, and P. A. van den Brandt K-ras oncogene mutations in sporadic colorectal cancer in The Netherlands Cohort Study Carcinogenesis, April 1, 2003; 24(4): 703 - 710. [Abstract] [Full Text] [PDF]
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S.-J. Park, A. Rashid, J.-H. Lee, S. G. Kim, S. R. Hamilton, and T.-T. Wu Frequent CpG Island Methylation in Serrated Adenomas of the Colorectum Am. J. Pathol., March 1, 2003; 162(3): 815 - 822. [Abstract] [Full Text] [PDF]
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B. Diergaarde, W. L. van Geloof, G. N.P. van Muijen, F. J. Kok, and E. Kampman Dietary factors and the occurrence of truncating APC mutations in sporadic colon carcinomas: a Dutch population-based study Carcinogenesis, February 1, 2003; 24(2): 283 - 290. [Abstract] [Full Text] [PDF]
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N. J. Shaheen, L. M. Silverman, T. Keku, L. B. Lawrence, E. M. Rohlfs, C. F. Martin, J. Galanko, and R. S. Sandler Association Between Hemochromatosis (HFE) Gene Mutation Carrier Status and the Risk of Colon Cancer J Natl Cancer Inst, January 15, 2003; 95(2): 154 - 159. [Abstract] [Full Text] [PDF]
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S. Tokudome, Y. Yokoyama, T. Kamiya, K. Seno, H. Okuyama, K. Kuriki, J. Cheng, T. Nakamura, T. Fujii, H. Ichikawa, et al. Rationale and Study Design of Dietary Intervention in Patients Polypectomized for Tumors of the Colorectum Jpn. J. Clin. Oncol., December 1, 2002; 32(12): 550 - 553. [Abstract] [Full Text] [PDF]
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K. Hemminki and K. Czene Attributable Risks of Familial Cancer from the Family-Cancer Database Cancer Epidemiol. Biomarkers Prev., December 1, 2002; 11(12): 1638 - 1644. [Abstract] [Full Text] [PDF]
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R. J. Mitchell, S. M. Farrington, M. G. Dunlop, and H. Campbell Mismatch Repair Genes hMLH1 and hMSH2 and Colorectal Cancer: A HuGE Review Am. J. Epidemiol., November 15, 2002; 156(10): 885 - 902. [Abstract] [Full Text] [PDF]
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E. G. Luebeck and S. H. Moolgavkar Multistage carcinogenesis and the incidence of colorectal cancer PNAS, November 12, 2002; 99(23): 15095 - 15100. [Abstract] [Full Text] [PDF]
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H. K. Roy, J. M. Gulizia, W. J. Karolski, A. Ratashak, M. F. Sorrell, and D. Tuma Ethanol Promotes Intestinal Tumorigenesis in the MIN Mouse Cancer Epidemiol. Biomarkers Prev., November 1, 2002; 11(11): 1499 - 1502. [Abstract] [Full Text] [PDF]
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