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J Med Genet. 1993 August; 30(8): 675–678.
PMCID: PMC1016497

Evaluation of molecular genetic diagnosis in the management of familial adenomatous polyposis coli: a population based study.


A population based clinical and molecular genetic study of familial adenomatous polyposis coli (FAPC) was performed to investigate the value of molecular genetic analysis and ophthalmological assessment in the presymptomatic diagnosis of FAPC. The point prevalence of affected patients was 2.62 x 10(-5) (1/38,000) and the minimum heterozygote prevalence was estimated at 3.8 x 10(-5) (1/26,000). Eight of 33 (24%) probands were new mutations. Forty-eight asymptomatic relatives at 50% prior risk aged between 10 and 40 years were assessed for risk modification with linked DNA markers: in nine subjects (18%) the family structure was unsuitable for linkage based analysis, but 32 subjects were informative with a panel of intragenic and closely linked markers (25 had a combined age/DNA related risk of < 1% (low risk group) and seven were at high risk (DNA predicted risk > 99%)). Ophthalmological assessment for CHRPEs showed that 27/43 (63%) affected patients and high risk relatives and 0/18 low risk relatives had more than three CHRPEs. Interfamilial variation in CHRPE expression was apparent. This study has shown that DNA based risk modification with intragenic and closely linked DNA markers is informative in most FAPC families. In addition to the clinical benefits of presymptomatic diagnosis for FAPC, the reduction in screening for low risk relatives (365 person years in the present study) means that molecular genetic diagnosis of FAPC is a cost effective procedure.

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  • Murday V, Slack J. Inherited disorders associated with colorectal cancer. Cancer Surv. 1989;8(1):139–157. [PubMed]
  • Kinzler KW, Nilbert MC, Vogelstein B, Bryan TM, Levy DB, Smith KJ, Preisinger AC, Hamilton SR, Hedge P, Markham A, et al. Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers. Science. 1991 Mar 15;251(4999):1366–1370. [PubMed]
  • Nishisho I, Nakamura Y, Miyoshi Y, Miki Y, Ando H, Horii A, Koyama K, Utsunomiya J, Baba S, Hedge P. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science. 1991 Aug 9;253(5020):665–669. [PubMed]
  • Groden J, Thliveris A, Samowitz W, Carlson M, Gelbert L, Albertsen H, Joslyn G, Stevens J, Spirio L, Robertson M, et al. Identification and characterization of the familial adenomatous polyposis coli gene. Cell. 1991 Aug 9;66(3):589–600. [PubMed]
  • Vasen HF, Griffioen G, Offerhaus GJ, Den Hartog Jager FC, Van Leeuwen-Cornelisse IS, Meera Khan P, Lamers CB, Van Slooten EA. The value of screening and central registration of families with familial adenomatous polyposis. A study of 82 families in The Netherlands. Dis Colon Rectum. 1990 Mar;33(3):227–230. [PubMed]
  • Järvinen HJ. Epidemiology of familial adenomatous polyposis in Finland: impact of family screening on the colorectal cancer rate and survival. Gut. 1992 Mar;33(3):357–360. [PMC free article] [PubMed]
  • MacDonald F, Morton DG, Rindl PM, Haydon J, Cullen R, Gibson J, Neoptolemos JP, Keighley MR, McKeown CM, Hultén M. Predictive diagnosis of familial adenomatous polyposis with linked DNA markers: population based study. BMJ. 1992 Apr 4;304(6831):869–872. [PMC free article] [PubMed]
  • Heighway J, Hoban PR, Wyllie AH. SspI polymorphism in sequence encoding 3' untranslated region of the APC gene. Nucleic Acids Res. 1991 Dec 25;19(24):6966–6966. [PMC free article] [PubMed]
  • Kraus C, Ballhausen WG. Two intragenic polymorphisms of the APC-gene detected by PCR and enzymatic digestion. Hum Genet. 1992 Mar;88(6):705–706. [PubMed]
  • Maher ER, Bentley E, Yates JR, Latif F, Lerman M, Zbar B, Affara NA, Ferguson-Smith MA. Mapping of the von Hippel-Lindau disease locus to a small region of chromosome 3p by genetic linkage analysis. Genomics. 1991 Aug;10(4):957–960. [PubMed]
  • Dunlop MG, Wyllie AH, Steel CM, Piris J, Evans HJ. Linked DNA markers for presymptomatic diagnosis of familial adenomatous polyposis. Lancet. 1991 Feb 9;337(8737):313–316. [PubMed]
  • Bülow S, Holm NV, Hauge M. The incidence and prevalence of familial polyposis coli in Denmark. Scand J Soc Med. 1986;14(2):67–74. [PubMed]
  • Bower C, Levitt S, Francis S. The Western Australian Familial Polyposis Registry. Med J Aust. 1989 Nov 20;151(10):557–560. [PubMed]
  • Rustin RB, Jagelman DG, McGannon E, Fazio VW, Lavery IC, Weakley FL. Spontaneous mutation in familial adenomatous polyposis. Dis Colon Rectum. 1990 Jan;33(1):52–55. [PubMed]
  • Herrera L, Carrel A, Rao U, Castillo N, Petrelli N. Familial adenomatous polyposis in association with thyroiditis. Report of two cases. Dis Colon Rectum. 1989 Oct;32(10):893–896. [PubMed]
  • Hockey KA, Mulcahy MT, Montgomery P, Levitt S. Deletion of chromosome 5q and familial adenomatous polyposis. J Med Genet. 1989 Jan;26(1):61–62. [PMC free article] [PubMed]
  • Cross I, Delhanty J, Chapman P, Bowles LV, Griffin D, Wolstenholme J, Bradburn M, Brown J, Wood C, Gunn A, et al. An intrachromosomal insertion causing 5q22 deletion and familial adenomatous polyposis coli in two generations. J Med Genet. 1992 Mar;29(3):175–179. [PMC free article] [PubMed]
  • Lindgren V, Bryke CR, Ozcelik T, Yang-Feng TL, Francke U. Phenotypic, cytogenetic, and molecular studies of three patients with constitutional deletions of chromosome 5 in the region of the gene for familial adenomatous polyposis. Am J Hum Genet. 1992 May;50(5):988–997. [PubMed]
  • Cachon-Gonzalez MB, Delhanty JD, Burn J, Tsioupra K, Davis MB, Attwood J, Chapman P. Linkage analysis in adenomatous polyposis coli: the use of four closely linked DNA probes in 20 UK families. J Med Genet. 1991 Oct;28(10):681–685. [PMC free article] [PubMed]
  • Tops CM, Wijnen JT, Griffioen G, von Leeuwen IS, Vasen HF, den Hartog Jager FC, Breukel C, Nagengast FM, van der Klift HM, Lamers CB, et al. Presymptomatic diagnosis of familial adenomatous polyposis by bridging DNA markers. Lancet. 1989 Dec 9;2(8676):1361–1363. [PubMed]
  • Cottrell S, Bicknell D, Kaklamanis L, Bodmer WF. Molecular analysis of APC mutations in familial adenomatous polyposis and sporadic colon carcinomas. Lancet. 1992 Sep 12;340(8820):626–630. [PubMed]
  • Walker AR, Whynes DK, Chamberlain JO, Hardcastle JD. The hospital costs of diagnostic procedures for colorectal cancer. J Clin Epidemiol. 1991;44(9):907–914. [PubMed]

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