Skip to main content Accessibility help
Hostname: page-component-7f7b94f6bd-vvt5l Total loading time: 0.855 Render date: 2022-07-01T05:51:05.865Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "useRatesEcommerce": false, "useNewApi": true } hasContentIssue true

17 - Genetics of colorectal cancer

Published online by Cambridge University Press:  17 August 2009

Alan Wright
MRC Human Genetics Unit, Edinburgh
Nicholas Hastie
MRC Human Genetics Unit, Edinburgh
Get access



Colorectal cancer is a major public health problem in the developed world and is becoming increasingly prevalent in developing countries. The current annual world incidence is around 950 000 cases (Globocan, 2000). It is the most common cause of early cancer death in the non-smoking population. Recent developments have led to the isolation of a number of moderate- to high-risk cancer susceptibility genes for the disease. Identifying people with high-risk alleles offers real opportunities for application of preventive measures. Intensive surveillance to detect early cancer, or even prevent cancer by polyp removal, can be targeted by genotype information. Surgical intervention and chemoprevention guided by genetic information are also likely to be part of future armaments used to combat the disease. The last ten years has seen a number of exciting developments in understanding key molecular events involved in colorectal cancer susceptibility, which are beginning to provide new insight into the fundamental basis of the disease. In this chapter we will describe the major advances and how they are impacting diagnosis and clinical management of colorectal cancer.

Colorectal cancer epidemiology

The multifactorial etiology of colorectal cancer involves environmental factors as well as genetic susceptibility (see Chapter 14). There are large differences in global prevalence of the disease, which is generally four times higher in developed countries than in developing countries (IARC, WHO, 1997). Incidence rates also vary according to ethnicity (American Cancer Society, 2002), however the observed variation between countries is primarily due to the role of environmental factors.

Genes and Common Diseases
Genetics in Modern Medicine
, pp. 245 - 267
Publisher: Cambridge University Press
Print publication year: 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


Aaltonen, L. A., Peltomaki, P., Leach, F. al. (1993). Clues to the pathogenesis of familial colorectal cancer. Science, 260, 812–16.CrossRefGoogle ScholarPubMed
Aaltonen, L. A., Peltomaki, P., Mecklin, al. (1994). Replication errors in benign and malignant tumours from hereditary non-polyposis colorectal cancer patients. Cancer Research, 54, 1645–8.Google Scholar
Aarnio, M., Mecklin, J.-P., Aaltonen, L. al. (1995). Life-time risk of different cancers in hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. International Journal of Cancer, 64, 430–3.CrossRefGoogle Scholar
Akiyama, Y., Sato, H., Yamada, al. (1997). Germ-line mutations of the hMSH6/GTBP gene in an atypical hereditary nonpolyposis colorectal cancer kindred. Cancer Research, 57, 3920–3.Google Scholar
Alberts, D. S., Martinez, M. E., Roe, D. al. (2000). Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas. Phoenix Colon Cancer Prevention Physicians' Network. New England Journal Medicine, 342, 1156–62.CrossRefGoogle ScholarPubMed
Alhopuro, P., Katajisto, P., Lehtonen, al. (2005). Mutation analysis of three genes encoding novel LKB1-interacting proteins, BRG1, STRADα, and MO25α, in Peutz-Jeghers syndrome. British Journal of Cancer, 92, 1126–9.CrossRefGoogle ScholarPubMed
Al-Tassan, N., Chmiel, N. H., Maynard, al. (2002). Inherited variants of MYH associated with somatic G:C–T:A mutations in colorectal tumors. Nature Genetics, 30, 227–32.CrossRefGoogle Scholar
American Cancer Society. ( Cancer facts and figures 2002.
Bapat, M., Xia, L., Madlensky, al. (1996). The genetic basis of Muir–Torre syndrome includes the hMLH1 locus. American Journal of Human Genetics, 59, 736–9.Google ScholarPubMed
Barth, A. I.M., Nathke, I. S. and Nelson, W. J. (1997). Cadherins, catenins and APC protein: interplay between cytoskeletal complexes and signaling pathways. Current Opinion in Cell Biology, 9, 683–90.CrossRefGoogle ScholarPubMed
Beck, N. E., Tomlinson, I. P. M., Homfray, al. (1997). Genetic testing is important in families with a history suggestive of hereditary non-polyposis colorectal even if the Amsterdam criteria are not fulfilled. British Journal of Surgery, 84, 233–7.CrossRefGoogle Scholar
Bellacosa, A., Cicchillitti, L., Schepis, al. (1999). MED1, a novel human methyl-CpG-binding endonuclease, interacts with DNA mismatch repair protein MLH1. Proceedings of the National Academy of Sciences of the USA, 96, 3969–74.CrossRefGoogle ScholarPubMed
Ben-Ze'ev, A. and Geiger, B. (1998). Differential molecular interactions of β-catenin and plakoglobin in adhesion, signaling and cancer. Current Opinion in Cell Biology, 10, 629–39.CrossRefGoogle ScholarPubMed
Bisgaard, M. L., Fenger, K., Bulow, al. (1994). Familial adenomatous polyposis (FAP): frequency, penetrance, and mutation rate. Human Mutation, 3, 121–5.CrossRefGoogle ScholarPubMed
Bodmer, W. F., Bailey, C. J., Bodmer, al. (1987). Localisation of the gene for familial adenomatous polyposis on chromosome 5. Nature, 328, 614–16.CrossRefGoogle Scholar
Boldogh, I., Milligan, D., Lee, M. al. (2001). hMYH cell cycle-dependent expression, subcellular localization and association with replication foci: evidence suggesting replication-coupled repair of adenine:8-oxoguanine mispairs. Nucleic Acids Research, 29, 2802–9.CrossRefGoogle ScholarPubMed
Bonelli, L., Martines, H., Conio, al. (1988). Family history of colorectal cancer as a risk factor for benign and malignant tumours of the large bowel. A case control study. International Journal of Cancer, 41, 513–17.Google ScholarPubMed
Bronner, C. E., Baker, S. M., Morrison, P. al. (1994). Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature, 368, 258–61.CrossRefGoogle ScholarPubMed
Bunz, F., Hwang, P. M., Torrance, al. (1999). Disruption of p53 in human cancer cells alters the responses to therapeutic agents. Journal of Clinical Investigation, 104, 263–9.CrossRefGoogle ScholarPubMed
Burt, R. W. (1996). Familial risk and colorectal cancer. Gastroenterology Clinics of North America, 25, 793–803.CrossRefGoogle ScholarPubMed
Cahill, D. P., Lengauer, C., Yu, al. (1998). Mutations of mitotic checkpoint genes in human cancers. Nature, 392, 300–3.CrossRefGoogle ScholarPubMed
Cannon-Albright, L. A., Solnick, M. H., Bishop, D. al. (1988). Common inheritance of susceptibility to colonic adenomatous polyps and associated colorectal cancers. New England Journal of Medicine, 319, 533–7.CrossRefGoogle ScholarPubMed
Carethers, J. M., Chauhan, D. P., Fink, al. (1999). Mismatch repair proficiency and in vitro response to 5-fluorouracil. Gastroenterology, 117, 123–31.CrossRefGoogle ScholarPubMed
Cheadle, J. P. and Sampson, J. R. (2003). Exposing the MYtH about base excision repair and human inherited disease. Human Molecular Genetics, 12, R159–R165.CrossRefGoogle ScholarPubMed
Cottrell, S., Bicknell, D., Kaklamanis, al. (1992). Molecular analysis of APC mutations in familial adenomatous polyposis and sporadic colon carcinomas. Lancet, 340, 626–30.CrossRefGoogle ScholarPubMed
Croitoru, M. E., Cleary, S. P., DiNicola, al. (2004). Association between biallelic and monoallelic germline MYH gene mutations and colorectal cancer risk. Journal of the National Cancer Institute, 96, 1631–4.CrossRefGoogle ScholarPubMed
Cui, H., Cruz-Correa, M., Giardiello, F. al. (2003). Loss of IGF2 imprinting: a potential marker of colorectal cancer risk. Science, 299, 1753–5.CrossRefGoogle ScholarPubMed
Cunningham, J. M., Christensen, E. R., Tester, D. al. (1998). Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability. Cancer Research, 58, 3455–60.Google ScholarPubMed
David, S. S. and Williams, S. D. (1998). Chemistry of glycosylases and endonucleases involved in base-excision Repair. Chemical Reviews, 98, 1221–61.CrossRefGoogle ScholarPubMed
de Jong, M. M., Nolte, I. M., Te Meerman, G. J. et al. (2005). Colorectal cancer and the CHEK2 1100delC mutation. Genes Chromosomes Cancer, 43, 377–82.CrossRef
Rosa, M., Fasano, C., Panariello, al. (2000). Evidence for a recessive inheritance of Turcot's syndrome caused by compound heterozygous mutations within the PMS2 gene. Oncogene, 19, 1719–23.CrossRefGoogle ScholarPubMed
Vos, M., Hayward, B. E., Picton, al. (2004). Novel PMS2 pseudogenes can conceal recessive mutations causing a distinctive childhood cancer syndrome. American Journal of Human Genetics, 74, 954–64.CrossRefGoogle ScholarPubMed
Wind, N., Dekker, M., Berns, al. (1995). Inactivation of the mouse Msh2 gene results in mismatch repair deficiency, methylation tolerance, hyperrecombination, and predisposition to cancer. Cell, 82, 321–30.CrossRefGoogle Scholar
Dietrich, W. F., Lander, E. S., Smith, J. al. (1993). Genetic identification of Mom-1, a major modifier locus affecting Min-induced intestinal neoplasia in the mouse. Cell, 75, 631–9.CrossRefGoogle Scholar
Dobbie, Z., Muller, H. and Scott, R. J. (1996). Secretory phospholipase A2 does not appear to be associated with phenotypic variation in familial adenomatous polyposis. Human Genetics, 98, 386–90.CrossRefGoogle Scholar
Dunlop, M. G., Farrington, S. M., Carothers, A. al. (1997). Cancer risk associated with germline DNA mismatch repair gene mutations. Human Molecular Genetics, 6, 105–10.CrossRefGoogle ScholarPubMed
Eccles, D. M., Luijt, R., Breukel, al. (1996). Hereditary desmoid disease due to a frameshift mutation at codon 1924 of the APC gene. American Journal of Human Genetics, 59, 1193–201.Google ScholarPubMed
Enholm, S., Hienonen, T., Suomalainen, al. (2003). Proportion and phenotype of MYH-associated colorectal neoplasia in a population-based series of Finnish colorectal cancer patients. American Journal of Pathology, 163, 827–32.CrossRefGoogle Scholar
Ewart-Toland, A., Briassouli, P., Koning, J. al. (2003). Identification of Stk6/STK15 as a candidate low-penetrance tumor-susceptibility gene in mouse and human. Nature Genetics, 34, 403–12.CrossRefGoogle ScholarPubMed
Ewart-Toland, A., Dai, Q., Gao, Y. al. (2005). Aurora-A/STK15 T+91A is a general low penetrance cancer susceptibility gene: a meta-analysis of multiple cancer types. Carcinogenesis, 26, 1368–73.Google Scholar
Farrington, S. M., Lin-Goerke, J., Ling, al. (1998). Systematic analysis of hMSH2 and hMLH1 in young colon cancer patients and controls. American Journal of Human Genetics, 63, 749–59.CrossRefGoogle ScholarPubMed
Farrington, S. M., McKinley, A. J., Carothers, A. al. (2002). Evidence for an age-related influence of microsatellite instability on colorectal cancer survival. International Journal of Cancer, 98, 844–50.CrossRefGoogle ScholarPubMed
Farrington, S. M., Tenesa, A., Barnetson, al. (2005). Germline susceptibility to colorectal cancer due to Base-Excision Repair Gene Defects. American Journal of Human Genetics, 77, 112–19.CrossRefGoogle ScholarPubMed
Fearon, E. R., Cho, K. R., Nigro, J. al. (1990). Identification of a chromosome 18q gene that is altered in colorectal cancers. Science, 247, 49–56.CrossRefGoogle ScholarPubMed
Fishel, R. (2001). The selection for mismatch repair defects in hereditary nonpolyposis colorectal cancer: revising the mutator hypothesis. Cancer Research, 61, 7369–74.Google ScholarPubMed
Fishel, R., Lescoe, M. K., Rao, M. R. al. (1993). The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell, 75, 1027–38.CrossRefGoogle ScholarPubMed
Fodde, R., Kuipers, J., Rosenberg, al. (2001). Mutations in the APC tumour suppressor gene cause chromosomal instability. Nature Cell Biology, 3, 433–8.CrossRefGoogle ScholarPubMed
Fuchs, C. S., Giovannucci, E. L., Colditz, G. al. (1999). Dietary fiber and the risk of colorectal cancer and adenoma in women. New England Journal of Medicine, 340, 169–76.CrossRefGoogle ScholarPubMed
Giacosa, A., Franceschi, S., Vecchia, al. (1999). Energy intake, overweight, physical exercise and colorectal cancer risk. European Journal of Cancer Prevention, 8 Supplement 1, S53–S60.CrossRefGoogle ScholarPubMed
Giardello, F. M., Welsh, S. B., Hamilton, S. al. (1987). Increased risk of cancer in the Peutz-Jeghers syndrome. New England Journal of Medicine, 316, 1511–14.CrossRefGoogle Scholar
Giardiello, F. M., Hamilton, S. R., Krush, A. al. (1993). Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. New England Journal of Medicine, 328, 1313–16.CrossRefGoogle ScholarPubMed
Giovannucci, E. (2001). An updated review of the epidemiological evidence that cigarette smoking increases risk of colorectal cancer. Cancer Epidemiology Biomarkers & Prevention, 10, 725–31.Google ScholarPubMed
Globocan. (2000). Cancer Incidence, Mortality and prevalence worldwide. IARC database, 2000. (
Grady, W. M. (2004). Genomic instability and colon cancer. Cancer Metastasis Reviews, 23, 11–27.CrossRefGoogle ScholarPubMed
Grieu, F., Malaney, S., Ward, al. (2003). Lack of association between CCND1 G870A polymorphism and the risk of breast and colorectal cancers. Anticancer Research, 23, 4257–9.Google ScholarPubMed
Grilley, M., Holmes, J., Yashar, B. and Modrich, P. (1990). Mechanisms of DNA-mismatch correction. Mutation Research, 26, 253–67.CrossRefGoogle Scholar
Groden, J., Gelbert, L., Thliveris, al. (1993). Mutational analysis of patients with adenomatous polyposis: identical inactivating mutations in unrelated individuals. American Journal of Human Genetics, 52, 263–72.Google ScholarPubMed
Gryfe, R., Kim, H., Hsieh, E. T. al. (2000). Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. New England Journal of Medicine, 342, 69–77.CrossRefGoogle ScholarPubMed
Gu, Y., Parker, A., Wilson, T. al. (2002). Human MutY homolog, a DNA glycosylase involved in base excision repair, physically and functionally interacts with mismatch repair proteins human MutS homolog 2/human MutS homolog 6. Journal of Biological Chemistry, 277, 11135–42.CrossRefGoogle ScholarPubMed
Guo, G., Wang, W. and Bradley, A. (2004). Mismatch repair genes identified using genetic screens in Blm-deficient embryonic stem cells. Nature, 429, 891–5.CrossRefGoogle ScholarPubMed
Hackman, P., Tannergard, P., Osei-Mensa, al. (1997). A compound heterozygote for two MLH1 missense mutations. Nature Genetics, 17, 135–6.CrossRefGoogle ScholarPubMed
Hahn, S. A., Schutte, M., Hoque, A. T. M. al. (1996). DPC4, A candidate tumor-suppressor gene at human-chromosome 18q21.1. Science, 271, 350–3.CrossRefGoogle ScholarPubMed
Hamilton, S. R., Parsons, R. E., Papadopoulos, al. (1995). The molecular basis of Turcot's syndrome. New England Journal of Medicine, 332, 839–47.CrossRefGoogle ScholarPubMed
Hahnloser, D., Petersen, G. M., Rabe, al. (2003). The APC E1317Q variant in adenomatous polyps and colorectal cancers. Cancer Epidemiology Biomarkers & Prevention, 12, 1023–8.Google ScholarPubMed
He, T.-C., Sparks, A. B., Rago, al. (1998). Identification of c-MYC as a target of the APC pathway. Science, 281, 1509–12.CrossRefGoogle ScholarPubMed
Hemminki, A., Markie, D., Tomlinson, al. (1998). A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature, 391, 184–7.CrossRefGoogle ScholarPubMed
Hienonen, T., Laiho, P., Salovaara, al. (2003). Little evidence for involvement of MLH3 in colorectal cancer predisposition. International Journal of Cancer, 106, 292–6.CrossRefGoogle ScholarPubMed
Horii, A., Han, H.-J., Shimada, al. (1994). Frequent replication errors at microsatellite loci in tumours of patients with multiple primary cancers. Cancer Research, 54, 3373–82.Google Scholar
Howe, J. R., Roth, S., Ringold, J. al. (1998). Mutations in the SMAD4/DPC4 gene in juvenile polyposis. Science, 280, 1086–8.CrossRefGoogle ScholarPubMed
Howe, J. R., Bair, J. L., Sayed, M. al. (2001). Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis. Nature Genetics, 28, 184–7.CrossRefGoogle Scholar
Huang, J., Papadopoulos, N., McKinley, A. al. (1996). APC mutations in colorectal tumors with mismatch repair deficiency. Proceedings of the National Academy of Sciences of the USA, 93, 9049–54.CrossRefGoogle ScholarPubMed
IARC, WHO (1997). Cancer incidence in five continents. Lyon: IARC Scientific Publications.
Ionov, Y., Peinado, M. A., Malkhosyan, al. (1993). Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature, 363, 558–61.CrossRefGoogle ScholarPubMed
Jaeger, E. E., Woodford-Richens, K. L., Lockett, al. (2003). An ancestral Ashkenazi haplotype at the HMPS/CRAC1 locus on 15q13-q14 is associated with hereditary mixed polyposis syndrome. American Journal of Human Genetics, 72, 1261–7.CrossRefGoogle ScholarPubMed
Jass, J. R., Smyrk, T. C., Stewart, S. al. (1994). Pathology of hereditary non-polyposis colorectal cancer. Anticancer Research, 14, 1631–4.Google ScholarPubMed
Jenne, D. E., Reimann, H., Nezu, al. (1998). Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nature Genetics, 18, 38–44.CrossRefGoogle Scholar
Jiricny, J., Hughes, M., Corman, al. (1988). A human 200-kDa protein binds selectively to DNA fragments containing GT mismatches. Proceedings of the National Academy of Sciences of the USA, 85, 8860–4.CrossRefGoogle Scholar
Joslyn, L., Carlson, M., Thliveris, al. (1991). Identification of deletion mutations and three new genes at the familial polyposis locus. Cell, 66, 601–13.CrossRefGoogle ScholarPubMed
Kaklamani, V. G., Hou, N., Bian, al. (2003). TGFBR1*6A and cancer risk: a meta-analysis of seven case-control studies. Journal of Clinical Oncology, 21, 3236–43.CrossRefGoogle ScholarPubMed
Kaplan, K. B., Burds, A. A., Swedlow, J. al. (2001). A role for the Adenomatous Polyposis Coli protein in chromosome segregation. Nature Cell Biology, 3, 429–32.CrossRefGoogle ScholarPubMed
Kemp, Z., Thirlwell, C., Sieber, al. (2004). An update on the genetics of colorectal cancer. Human Molecular Genetics, 13, 177–85.CrossRefGoogle ScholarPubMed
Kinzler, K. W., Nilbert, M. C., Su, al. (1991). Identification of FAP locus genes from chomosome 5q21. Science, 253, 661–4.CrossRefGoogle Scholar
Kilpivaara, O., Laiho, P., Aaltonen, L. A. and Nevanlinna, H. (2003). CHEK2 1100delC and colorectal cancer. Journal of Medical Genetics, 40, e110.CrossRefGoogle Scholar
Koi, M., Umar, A., Chauhan, D. al. (1994). Human chromosome 3 corrects mismatch repair deficiency and microsatellite instability and reduces N-methyl-N′-nitro-N-nitrosoguanidine tolerance in colon tumor cells with homozygous hMLH1 mutation. Cancer Research, 54, 4308–14.Google ScholarPubMed
Kolodner, R., Hall, N., Lipford, al. (1994). Structure of the human MSH2 locus and analysis of two Muir–Torre kindreds for MSH2 mutations. Genomics, 24, 516–26.CrossRefGoogle ScholarPubMed
Kong, S., Wei, Q., Amos, C. al. (2001). Cyclin D1 polymorphism and increased risk of colorectal cancer at young age. Journal of the National Cancer Institute, 93, 1106–8.CrossRefGoogle ScholarPubMed
Vecchia, C., Negri, E., Decarli, al. (1997). Diabetes mellitus and colorectal cancer risk. Cancer Epidemiology Biomarkers & Prevention, 6, 1007–10.Google ScholarPubMed
Laiho, P., Hienonen, T., Karhu, al. (2003). Genome-wide allelotyping of 104 Finnish colorectal cancers reveals an excess of allelic imbalance in chromosome 20q in familial cases. Oncogene, 22, 2206–14.CrossRefGoogle ScholarPubMed
Laken, S. J., Petersen, G. M., Gruber, S. al. (1997). Familial colorectal cancer in Ashkenazim due to a hypermutable tract in APC. Nature Genetics, 17, 79–83.CrossRefGoogle ScholarPubMed
Lamlum, H., Al Tassan, N., Jaeger, al. (2000). Germline APC variants in patients with multiple colorectal adenomas, with evidence for the particular importance of E1317Q. Human Molecular Genetics, 9, 2215–21.CrossRefGoogle ScholarPubMed
Lammi, L., Arte, S., Somer, al. (2004). Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer. American Journal of Human Genetics, 74, 1043–50.CrossRefGoogle ScholarPubMed
Marchand, L., Seifried, A., Lum-Jones, al. (2003). Association of the cyclin D1 A870G polymorphism with advanced colorectal cancer. Journal of American Medical Association, 290, 2843–8.CrossRefGoogle ScholarPubMed
Leach, F. S., Nicolaides, N. C., Papadopolous, al. (1993). Mutations of a MutS homolog in hereditary non-polyposis colorectal cancer. Cell, 75, 1215–25.CrossRefGoogle Scholar
Leppert, M., Dobbs, M., Scambler, al. (1987). The gene for familial polyposis maps to the long arm of chromosome 5. Science, 238, 1411–13.CrossRefGoogle Scholar
Li, D. M. and Sun, H. (1997). TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta. Cancer Research, 57, 2124–9.Google ScholarPubMed
Liaw, D., Marsh, D. J., Li, al. (1997). Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nature Genetics, 16, 64–7.CrossRefGoogle ScholarPubMed
Lichtenstein, P., Holm, N. V., Verkasalo, P. al. (2000). Environmental and heritable factors in the causation of cancer–analyses of cohorts of twins from Sweden, Denmark, and Finland. New England Journal of Medicine, 343, 78–85.CrossRefGoogle Scholar
Lindblom, A., Tannergard, P., Werelius, B. and Nordenskjold, M. (1993). Genetic mapping of a second locus predisposing to hereditary non-polyposis colon cancer. Nature Genetics, 5, 279–82.CrossRefGoogle ScholarPubMed
Lipkin, S. M., Wang, V., Jacoby, al. (2000). MLH3: a DNA mismatch repair gene associated with mammalian microsatellite instability. Nature Genetics, 24, 27–35.CrossRefGoogle ScholarPubMed
Lipkin, S. M., Rozek, L. S., Rennert, al. (2003). The MLH1 D132H variant is associated with susceptibility to sporadic colorectal cancer. Nature Genetics, 36, 694–9.CrossRefGoogle Scholar
Liu, B., Farrington, S. M., Petersen, G. al. (1995). Genetic instability occurs in the majority of young patients with colorectal cancer. Nature Medicine, 2, 348–52.CrossRefGoogle Scholar
Lothe, R. A., Peltomaki, P., Meling, G. al. (1993). Genomic instability in colorectal cancer: relationship to clinicopathological variables and family history. Cancer Research, 53, 5849–52.Google ScholarPubMed
Lu, S.-L., Kawabata, M., Imamura, al. (1998). HNPCC associated with germline mutation in the TGF-beta type II receptor gene. Nature Genetics, 19, 17–18.CrossRefGoogle ScholarPubMed
Lynch, H. T., Kimberling, W. J., Albano, W. al. (1985). Hereditary nonpolyposis colorectal cancer (Lynch Syndromes 1 and 2). 1. Clinical description of resource. Cancer, 56, 934–8.3.0.CO;2-I>CrossRefGoogle Scholar
MacPhee, M., Chepenik, K. P., Liddell, R. al. (1995). The secretory phospholipase A2 gene is a candidate for the Mom1 locus, a major modifier of Apc(Min)-induced intestinal neoplasia. Cell, 81, 957–66.CrossRefGoogle Scholar
Mandl, M., Paffenholz, R., Friedl, al. (1994). Frequency of common and novel inactivating APC mutations in 202 families with familial adenomatous polyposis. Human Molecular Genetics, 3, 181–4.CrossRefGoogle Scholar
Markowitz, S., Wang, J., Myeroff, al. (1995). Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. Science, 268, 1336–8.CrossRefGoogle ScholarPubMed
Matsumine, A., Ogai, A., Senda, al. (1996). Binding of APC to the human homolog of the Drosophila discs large tumour suppressor protein. Science, 272, 1020–3.CrossRefGoogle Scholar
Mazurek, A., Berardini, M. and Fishel, R. (2002). Activation of human MutS homologs by 8-oxo-guanine DNA damage. Journal of Biological Chemistry, 277, 8260–6.CrossRefGoogle ScholarPubMed
Meijers-Heijboer, H., Ouweland, A., Klijn, al. (2002). Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in non-carriers of BRCA1 or BRCA2 mutations. Nature Genetics, 31, 55–9.Google ScholarPubMed
Miyaki, M., Konishi, M., Tanaka, al. (1997). Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer. Nature Genetics, 17, 271–2.CrossRefGoogle ScholarPubMed
Moser, A. R., Dove, W. F., Roth, K. al. (1992). The Min (Multiple Intestinal Neoplasia) Mutation: Its effect on gut epithelial cell differentiation and interaction with a modifier system. Journal of Cell Biology, 116, 1517–26.CrossRefGoogle ScholarPubMed
Moser, A. R., Pitot, H. C. and Dove, W. F. (1990). A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science, 247, 322–4.CrossRefGoogle ScholarPubMed
Munemitsu, S., Souza, B., Muller, al. (1994). The APC gene product associates with microtubules in vivo and promotes their assembly in vitro. Cancer Research, 54, 3676–81.Google ScholarPubMed
Nagase, H., Miyoshi, Y., Horii, al. (1992). Correlation between the location of germ-line mutations in the APC gene and the number of colorectal polyps in familial adenomatous polyposis patients. Cancer Research, 52, 4055–7.Google ScholarPubMed
Nagase, H. and Nakamura, Y. (1993). Mutations of the APC (adenomatous polyposis coli) gene. Human Mutation, 2, 425–34.CrossRefGoogle ScholarPubMed
Nathke, I.S., Adams, C.L., Polakis, al. (1996). The adenomatous polyposis coli (APC) tumour suppressor protein localizes to plasma membrane sites involved in active cell migration. Journal of Cell Biology, 134, 165–80.CrossRefGoogle ScholarPubMed
Nelen, M. R., Padberg, G. W., Peeters, E. al. (1996). Localization of the gene for Cowden disease to chromosome 10q22–23. Nature Genetics, 13, 114–16.CrossRefGoogle ScholarPubMed
Nicolaides, N. C., Papadopoulos, N., Wei, al. (1994). Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. Nature, 371, 75–80.CrossRefGoogle ScholarPubMed
Ohtsubo, T., Nishioka, K., Imaiso, al. (2000). Identification of human MutY homolog (hMYH) as a repair enzyme for 2-hydroxyadenine in DNA and detection of multiple forms of hMYH located in nuclei and mitochondria. Nucleic Acids Research, 28, 1355–64.CrossRefGoogle ScholarPubMed
Olschwang, S., Serova-Sinilnikova, O. M., Lenoir, G. M. and Thomas, G. (1998). PTEN germ-line mutations in juvenile polyposis coli. Nature Genetics, 18, 12–14.CrossRefGoogle ScholarPubMed
Ouyang, H., Furukawa, T., Abe, al. (1998). The BAX gene, the promoter of apoptosis, is mutated in genetically unstable cancers of the colorectum, stomach, and endometrium. Clinical Cancer Research, 4, 1071–4.Google ScholarPubMed
Papadopolous, N., Nicolaides, N. C., Wei, al. (1994). Mutation of a mutL homolog in hereditary colon cancer. Science, 263, 1625–9.CrossRefGoogle Scholar
Parker, A., Gu, Y., Mahoney, al. (2001). Human homolog of the MutY repair protein (hMYH) physically interacts with proteins involved in long patch DNA base excision repair. Journal of Biological Chemistry, 276, 5547–55.CrossRefGoogle ScholarPubMed
Parkin, D. M. (1992). Studies of cancer in migrant populations: methods and interpretation. Reviews in Epidemiology Sante Publique, 40, 410–24.Google ScholarPubMed
Paul, P., Letteboer, T., Gelbert, al. (1993). Identical APC exon 15 mutations result in a variable phenotype in familial adenomatous polyposis. Human Molecular Genetics, 2, 925–31.CrossRefGoogle Scholar
Peltomaki, L., Aaltonen, L. A., Sistonen, al. (1993). Genetic mapping of a locus predisposing to human colorectal cancer. Science, 260, 810–12.CrossRefGoogle ScholarPubMed
Peterlongo, P., Howe, L. R., Radice, al. (2005). Germline mutations of AXIN2 are not associated with nonsyndromic colorectal cancer. Human Mutation, 25, 498–500.CrossRefGoogle Scholar
Polakis, P. (1999). The oncogenic activation of beta-catenin. Current Opinion in Genetics & Development, 9, 15–21.CrossRefGoogle ScholarPubMed
Potter, J. D. (1999). Colorectal cancer: molecules and populations. Journal of the National Cancer Institute, 91, 916–32.CrossRefGoogle ScholarPubMed
Ricciardone, M. D., Oezcelik, T., Cevher, al. (1999). Human MLH1 deficiency predisposes to hematological malignancy and neurofibromatosis type 1. Cancer Research, 59, 290–3.Google ScholarPubMed
Rijnkels, J. M., Hollanders, V. M., Woutersen, R. al. (1998). Absence of an inhibitory effect of a vegetables-fruit mixture on the initiation and promotion phases of azoxymethane-induced colorectal carcinogenesis in rats fed low- or high-fat diets. Nutrition & Cancer, 30, 124–9.CrossRefGoogle ScholarPubMed
Sakatani, T., Kaneda, A., Iacobuzio-Donahue, C. al. (2005). Loss of imprinting of Igf2 alters intestinal maturation and tumorigenesis in mice. Science, 307, 1976–8.CrossRefGoogle ScholarPubMed
Sampson, J. R., Dolwani, S., Jones, al. (2003). Autosomal recessive colorectal adenomatous polyposis due to inherited mutations of MYH. Lancet, 362, 39–41.CrossRefGoogle ScholarPubMed
Schatzkin, A., Lanza, E., Corle, al. (2000). Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. Polyp Prevention Trial Study Group. New England Journal of Medicine, 342, 1149–55.CrossRefGoogle ScholarPubMed
Sharp, L. and Little, J. (2004). Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a HuGE review. American Journal of Epidemiology, 159, 423–43.CrossRefGoogle ScholarPubMed
Shimodaira, H., Filosi, N., Shibata, al. (1998). Functional analysis of human MLH1 mutations in Saccharomyces cerevisiae. Nature Genetics, 19, 384–9.CrossRefGoogle ScholarPubMed
Sieber, O. M., Lipton, L., Crabtree, al. (2003). Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. New England Journal of Medicine, 348, 791–9.CrossRefGoogle ScholarPubMed
Sirard, C., Pompa, J. L., Elia, al. (1998). The tumor suppressor gene Smad4/Dpc4 is required for gastrulation and later for anterior development of the mouse embryo. Genes and Development, 12, 107–19.CrossRefGoogle ScholarPubMed
Slattery, M. L., Samowtiz, W., Ballard, al. (2001). A molecular variant of the APC gene at codon 1822: its association with diet, lifestyle, and risk of colon cancer. Cancer Research, 61, 1000–4.Google ScholarPubMed
Slattery, M. L., Samowtiz, W., Ma, al. (2004). CYP1A1, cigarette smoking, and colon and rectal cancer. American Journal of Epidemiology, 160, 842–52.CrossRefGoogle ScholarPubMed
Slattery, M. L., Sweeney, C., Murtaugh, al. (2005). Associations between ApoE genotype and colon and rectal cancer. Carcinogenesis, (In press (E-pub, April)).Google Scholar
Smith, K. J., Johnson, K. A., Bryan, T. al. (1993). The APC gene product in normal and tumour cells. Proceedings of the National Academy of Sciences of the USA, 90, 2846–50.CrossRefGoogle Scholar
Smith, K. J., Levy, D. B., Maupin, al. (1994). Wild-type but not mutant APC associates with microtubule cytoskeleton. Cancer Research, 54, 3672–5.Google Scholar
Stark, L. A. and Dunlop, M. G. (2005). Nucleolar sequestration of Rel A (p65) regulates NF-κB driven transcription and apoptosis. Molecular and Cellular Biology, 25, 5985–6004.CrossRefGoogle Scholar
Steinbach, G., Lynch, P. M., Phillips, R. al. (2000). The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. New England Journal of Medicine, 342, 1946–52.CrossRefGoogle ScholarPubMed
Strand, M., Prolla, T. A., Liskay, R. al. (1993). Destabilization of tracts of simple repetitive DNA in yeasts by mutations affecting DNA mismatch repair. Nature, 365, 274–6.CrossRefGoogle Scholar
Su, L.-K., Burrell, M., Hill, D. al. (1995). APC binds to the novel protein EB1. Cancer Research, 55, 2972–7.Google ScholarPubMed
Su, L.-K., Johnson, K. A., Smith, K. al. (1993). Association between wild-type and mutant APC gene products. Cancer Research, 53, 2728–31.Google ScholarPubMed
Suter, C. M., Martin, D. I. and Ward, R. L. (2004). Germline epimutation of MLH1 in individuals with multiple cancers. Nature Genetics, 36, 497–501.CrossRefGoogle ScholarPubMed
Thibodeau, S. N., Bren, G. and Schaid, D. (1993). Microsatellite instability in cancer of the proximal colon. Science, 260, 816–19.CrossRefGoogle ScholarPubMed
Thomas, H. J. W., Whitelaw, S. C., Cottrell, S. al. (1996). Genetic mapping of hereditary mixed polyposis syndrome to chromosome 6q. American Journal of Human Genetics, 58, 770–6.Google ScholarPubMed
Tomlinson, I. P. M., Neale, K., Talbot, I. al. (1996). A modifying locus for familial adenomatous polyposis may be present on chromosome 1p35-p36. Journal of Medical Genetics, 33, 268–73.CrossRefGoogle ScholarPubMed
Toyota, M., Ahuja, N., Ohe-Toyota, al. (1999). CpG island methylator phenotype in colorectal cancer. Proceedings of the National Academy of Sciences of the USA, 96, 8681–6.CrossRefGoogle ScholarPubMed
Trojan, J., Zeuzem, S., Randolph, al. (2002). Functional analysis of hMLH1 variants and HNPCC-related mutations using a human expression system. Gastroenterology, 122, 211–19.CrossRefGoogle ScholarPubMed
Houven van Oordt, C. W., Smits, R., Schouten, T. al. (1999). The genetic background modifies the spontaneous and X-ray-induced tumor spectrum in the Apc1638N mouse model. Genes, Chromosomes & Cancer, 24, 191–8.3.0.CO;2-L>CrossRefGoogle ScholarPubMed
Kranen, H. J., Iersel, P. W., Rijnkels, J. al. (1998). Effects of dietary fat and a vegetable-fruit mixture on the development of intestinal neoplasia in the ApcMin mouse. Carcinogenesis, 19, 1597–601.CrossRefGoogle Scholar
Vasen, H. F. A., Wijnen, J. T., Menko, F. al. (1996). Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis. Gastroenterology, 110, 1020–7.CrossRefGoogle ScholarPubMed
Venesio, T., Molatore, S., Cattaneo, al. (2004). High frequency of MYH gene mutations in a subset of patients with familial adenomatous polyposis. Gastroenterology, 126, 1681–5.CrossRefGoogle Scholar
Wang, L., Baudhuin, L. M., Boardman, L. al. (2004). MYH mutations in patients with attenuated and classic polyposis and with young-onset colorectal cancer without polyps. Gastroenterology, 127, 9–16.CrossRefGoogle ScholarPubMed
Wang, Q., Lasset, C., Desseigne, al. (1999). Neurofibromatosis and early onset of cancers in hMLH1-deficient children. Cancer Research, 59, 294–7.Google ScholarPubMed
Watanabe, A., Ikejima, M., Suzuki, al. (1996). Genomic organization and expression of the human MSH3 gene. Genomics, 31, 311–18.CrossRefGoogle ScholarPubMed
Wei, K., Kucherlapati, R. and Edelmann, W. (2002). Mouse models for human DNA mismatch-repair gene defects. Trends in Molecular Medicine, 8, 346–53.CrossRefGoogle ScholarPubMed
Wiebauer, K. M. and Jiricny, J. (1990). Mismatch-specific thymine DNA glysosylase and DNA polymerase B mediate the correction of G.T mispairs in nuclear extracts from human cells. Proceedings of the National Academy of Sciences of the USA, 87, 5842–5.CrossRefGoogle Scholar
Wijnen, J. T., Leeuw, W., Vasen, al. (1999). Familial endometrial cancer in female carriers of MSH6 germline mutations. Nature Genetics, 23, 142–4.CrossRefGoogle ScholarPubMed
World Cancer Research Fund Panel (Chair: J. D. Potter). (2001). Diet, nutrition, and the prevention of cancer. (
Yang, G., Scherer, S. J., Shell, S. al. (2004). Dominant effects of an Msh6 missense mutation on DNA repair and cancer susceptibility. Cancer Cell, 6, 139–50.CrossRefGoogle ScholarPubMed
Yang, K., Edelmann, W., Fan, al. (1998). Dietary modulation of carcinoma development in a mouse model for human familial adenomatous polyposis. Cancer Research, 58, 5713–17.Google Scholar
Zhang, H., Richards, B., Wilson, al. (1999). Apoptosis induced by overexpression of hMSH2 or hMLH1. Cancer Research, 59, 3021–7.Google ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the or variations. ‘’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats