title: Extracolonic features of familial adenomatous polyposis in patients with sporadic colorectal cancer.
abstract: We have investigated the occurrence of attenuated extracolonic manifestations (AEMs) of familial adenomatous polyposis (FAP) in patients with non-polyposis colorectal cancer. In a prospective case-control study, we observed that significantly more colorectal cancer patients exhibited AEM than did age and sex-matched controls (19.5% vs 7.5%, P < 0.004). However patients with AEMs do not have occult FAP, as we found no heterozygous adenomatous polyposis coli (APC) gene mutations despite extensive analysis of constitutional DNA. Genome-wide DNA replication errors (RERs) occur in a proportion of colorectal cancers, particularly right-sided lesions and in almost all tumours from hereditary non-polyposis colorectal cancer (HNPCC) patients. As AEMs have been reported in familial colon cancer cases, we investigated the relationship of AEMs to tumour RER phenotype. There was indeed an excess of AEMs in patients with right-sided tumours (30.2% of 53 patients vs 14.7% of 116 patients, P < 0.03) and in those with RER tumours (3 out of 12 patients with RER tumours vs none out of 21 patients with non-RER tumours, P < 0.05). Two patients with AEM were from HNPCC families compared with none of those without AEM (P < 0.05). The association of AEMs with colorectal cancer is intriguing, and we speculate that it may be a manifestation of mutational mosaicism of the APC gene, perhaps associated with a constitutional defect in DNA mismatch pair.
authors.affiliation: University of Edinburgh, Department of Clinical Surgery, Royal Infirmary, UK.
authors.forename: M G
authors.initials: MG
authors.lastname: Dunlop
authors.forename: S M
authors.initials: SM
authors.lastname: Farrington
authors.forename: V J
authors.initials: VJ
authors.lastname: Bubb
authors.forename: C
authors.initials: C
authors.lastname: Cunningham
authors.forename: M
authors.initials: M
authors.lastname: Wright
authors.forename: L J
authors.initials: LJ
authors.lastname: Curtis
authors.forename: Z A
authors.initials: ZA
authors.lastname: Butt
authors.forename: E
authors.initials: E
authors.lastname: Wright
authors.forename: B W
authors.initials: BW
authors.lastname: Fleck
authors.forename: D
authors.initials: D
authors.lastname: Redhead
authors.forename: R
authors.initials: R
authors.lastname: Mitchell
authors.forename: J B
authors.initials: JB
authors.lastname: Rainey
authors.forename: I M
authors.initials: IM
authors.lastname: Macintyre
authors.forename: D C
authors.initials: DC
authors.lastname: Carter
authors.forename: A H
authors.initials: AH
authors.lastname: Wyllie
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000150:complications* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004261:DNA Replication; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D017491:Genes, APC / Q000235:genetics*; D006801:Humans; D006984:Hypertrophy / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010641:Phenotype; D010857:Pigment Epithelium of Eye / Q000473:pathology*; D011446:Prospective Studies
chemical_list: D004273:DNA, Neoplasm