title: Familial colorectal cancer type X: polyp burden and cancer risk  stratification via a family history score.
abstract: BACKGROUND
  Patients fulfilling Amsterdam-1 criteria without mismatch repair deficiency (termed familial colorectal cancer type X (FCC type X)) were reported to have lower cancer risks than classic Lynch syndrome. This study investigates the polyp and cancer burden of this population and demonstrates relationships with a family history score (FHS).
  
  
  METHODS
  The Jagelman Registry was queried for patients meeting Amsterdam criteria with microsatellite stable/low colorectal cancers. The risk of colorectal neoplasia was ascertained using a published FHS. Polyp distribution, histology and cumulative counts as well as extra-colonic tumours in the pedigree were reviewed.
  
  
  RESULTS
  Twenty-one patients (9 males, 12 females) met study criteria. The median lifetime polyp count was 3 (range 1–36). FHS 8 (80%) was significantly associated with an increased risk of colorectal cancer compared with those with scores <8 who are more likely to develop polyps (P < 0.01). Twelve patients (57%) had predominantly left-sided polyps. Ten colorectal cancers (7 left-sided, 3 right-sided) were diagnosed at a median age of 48 (range 30–74) years. Only three tumours were mucinous or demonstrated tumour-infiltrating lymphocytes, typical of high microsatellite instability tumours. All patients had family history of colorectal cancers (CRCs) and at least 10 patients had a family history of uterine or breast cancer. One patient was found to have hyperplastic polyposis syndrome.
  
  
  CONCLUSIONS
  FCC type X likely represents a heterogenous group of as yet undefined CRC predispositions. The polyp burden and cancer risk are variable and can be somewhat delineated according to an FHS.
authors.affiliation: Department of Colorectal Surgery, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Poh-Koon
authors.initials: PK
authors.lastname: Koh
authors.forename: Matthew
authors.initials: M
authors.lastname: Kalady
authors.forename: Marek
authors.initials: M
authors.lastname: Skacel
authors.forename: Susan
authors.initials: S
authors.lastname: Fay
authors.forename: Ellen
authors.initials: E
authors.lastname: McGannon
authors.forename: Janet
authors.initials: J
authors.lastname: Shenal
authors.forename: Loretta
authors.initials: L
authors.lastname: Arroyo
authors.forename: Kathy
authors.initials: K
authors.lastname: Toderick
authors.forename: James
authors.initials: J
authors.lastname: Church
mesh_terms: D000328:Adult; D000368:Aged; D003111:Colonic Polyps / Q000235:genetics / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D053843:DNA Mismatch Repair; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment