FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 322:904-908 March 29, 1990 Number 13 Next

	Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

Abstract

We studied a large kindred with a history of colorectal cancer of early onset. Proctosigmoidoscopic examination of 51 family members identified only 2 with familial polyposis coli, which strongly predisposes those who have it to colorectal cancer and which is defined as the presence of more than 100 polyps in the colon. However, eight family members had 2 to 40 colonic polyps. We suspected that in this family, colorectal cancer was the result of a mutation in the gene on chromosome 5 that is responsible for familial polyposis coli. To test our hypothesis, we obtained genotypic information on 81 family members with respect to seven polymorphic DNA markers previously shown to be linked to the locus for familial polyposis coli. Multilocus analysis of the data demonstrated genetic linkage (lod score, 5.58) between these markers and the locus responsible for the defined syndrome of colonic polyps or colorectal cancer in this kindred. These findings constitute evidence that the genetic defect in this family is a mutation in the gene that causes familial polyposis coli. We conclude that mutations at the genetic locus for familial polyposis coli may be the cause of other, more subtle syndromes involving an inherited susceptibility to colonic adenomatous polyps and colorectal cancer.

Source Information

Howard Hughes Medical Institute, Salt Lake City, UT.

This article has been cited by other articles:

• Ong, E. S., Alassas, M. A., Bogner, P. N., Bullard Dunn, K., Chey, W. Y., Gibbs, J. F. (2008). Total Gastrectomy for Gastric Dysplasia in a Patient With Attenuated Familial Adenomatous Polyposis Syndrome. JCO 26: 3641-3642 [Full Text]  
• Braff, D. L., Freedman, R., Schork, N. J., Gottesman, I. I. (2007). Deconstructing Schizophrenia: An Overview of the Use of Endophenotypes in Order to Understand a Complex Disorder. Schizophr Bull 33: 21-32 [Abstract] [Full Text]  
• Chetty, R, Salahshor, S, Bapat, B, Berk, T, Croitoru, M, Gallinger, S (2005). Intraductal papillary mucinous neoplasm of the pancreas in a patient with attenuated familial adenomatous polyposis. J. Clin. Pathol. 58: 97-101 [Abstract] [Full Text]  
• Hahnloser, D., Petersen, G. M., Rabe, K., Snow, K., Lindor, N. M., Boardman, L., Koch, B., Doescher, D., Wang, L., Steenblock, K., Thibodeau, S. N. (2003). The APC E1317Q Variant in Adenomatous Polyps and Colorectal Cancers. Cancer Epidemiol. Biomarkers Prev. 12: 1023-1028 [Abstract] [Full Text]  
• Gottesman, I. I., Gould, T. D. (2003). The Endophenotype Concept in Psychiatry: Etymology and Strategic Intentions. Am. J. Psychiatry 160: 636-645 [Abstract] [Full Text]  
• Heppner Goss, K., Trzepacz, C., Tuohy, T. M. F., Groden, J. (2002). Attenuated APC alleles produce functional protein from internal translation initiation. Proc. Natl. Acad. Sci. USA 99: 8161-8166 [Abstract] [Full Text]  
• Wagner, A, Hendriks, Y, Meijers-Heijboer, E J, de Leeuw, W J F, Morreau, H, Hofstra, R, Tops, C, Bik, E, Bröcker-Vriends, A H J T, van der Meer, C, Lindhout, D, Vasen, H F A, Breuning, M H, Cornelisse, C J, van Krimpen, C, Niermeijer, M F, Zwinderman, A H, Wijnen, J, Fodde, R (2001). Atypical HNPCC owing to MSH6 germline mutations: analysis of a large Dutch pedigree. J. Med. Genet. 38: 318-322 [Abstract] [Full Text]  
• Fearnhead, N. S., Britton, M. P., Bodmer, W. F. (2001). The ABC of APC. Hum Mol Genet 10: 721-733 [Abstract] [Full Text]  
• Potter, J. D. (1999). Colorectal Cancer: Molecules and Populations. JNCI J Natl Cancer Inst 91: 916-932 [Abstract] [Full Text]  
• Brensinger, J D, Laken, S J, Luce, M C, Powell, S M, Vance, G H, Ahnen, D J, Petersen, G M, Hamilton, S R, Giardiello, F M (1998). Variable phenotype of familial adenomatous polyposis in pedigrees with 3' mutation in the APC gene. Gut 43: 548-552 [Abstract] [Full Text]  
• Shoemaker, A. R., Moser, A. R., Midgley, C. A., Clipson, L., Newton, M. A., Dove, W. F. (1998). A resistant genetic background leading to incomplete penetrance of intestinal neoplasia and reduced loss of heterozygosity in ApcMin/+ mice. Proc. Natl. Acad. Sci. USA 95: 10826-10831 [Abstract] [Full Text]  
• Thompson, M.B. (1997). The Min Mouse: A Genetic Model for Intestinal Carcinogenesis. Toxicol Pathol 25: 329-332  
• Samowitz, W. S., Burt, R. W., Leppert, M., Dupuis, M.J.M., Verellen-Dumoulin, C., Coyle, T., Ellis, M. F., Whitelaw, S., Rustgi, A. K. (1995). Gastrointestinal Polyposis and Nonpolyposis Syndromes. NEJM 332: 1518-1520 [Full Text]  
• Copper, M. P., Jovanovic, A., Nauta, J. J. P., Braakhuis, B. J. M., de Vries, N., van der Waal, I., Snow, G. B. (1995). Role of Genetic Factors in the Etiology of Squamous Cell Carcinoma of the Head and Neck. Arch Otolaryngol Head Neck Surg 121: 157-160 [Abstract]  
• Rustgi, A. K. (1994). Hereditary Gastrointestinal Polyposis and Nonpolyposis Syndromes. NEJM 331: 1694-1702 [Full Text]  
• Liu, E. T. (1993). From the Molecule to Public Health. NEJM 329: 2028-2029 [Full Text]  
• Su, L., Kinzler, K., Vogelstein, B, Preisinger, A., Moser, A., Luongo, C, Gould, K., Dove, W. (1992). Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science 256: 668-670 [Abstract]  
• Kinzler, K., Nilbert, M., Su, L., Vogelstein, B, Bryan, T., Levy, D., Smith, K., Preisinger, A., Hedge, P, McKechnie, D, et, al. (1991). Identification of FAP locus genes from chromosome 5q21. Science 253: 661-665 [Abstract]  
• Nishisho, I, Nakamura, Y, Miyoshi, Y, Miki, Y, Ando, H, Horii, A, Koyama, K, Utsunomiya, J, Baba, S, Hedge, P (1991). Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 253: 665-669 [Abstract]