title: Evaluation of the colorectal cancer risk conferred by rare UNC5C alleles.
abstract: OBJECTIVE
  To evaluate the risk associated with variants of the UNC5C gene recently suspected to predispose to familial colorectal cancer (CRC).
  
  
  METHODS
  We screened patients with familial CRC forms as well as patients with sporadic CRCs. In a first time, we analyzed exon 11 of the UNC5C gene in 120 unrelated patients with suspected hereditary CRC, 58 patients with suspected Lynch-associated cancer or polyposis, and 132 index cases of Lynch syndrome families with a characterized mutation in a DNA mismatch repair (MMR). Next, 1023 patients with sporadic CRC and 1121 healthy individuals were screened for the variants identified in patients with familial cancer.
  
  
  RESULTS
  Of 120 patients with familial CRC of unknown etiology, one carried the previously reported mis-sense mutation p.Arg603Cys (R603C) and another exhibited the unreported variant of unknown significance p.Thr617Ile (T617I). The p.Ala628Lys (A628K) mutation previously described as the main UNC5C risk variant for familial CRC was not detected in any cases of familial CRC of unknown etiology, but was present in a patient with familial gastric cancer and in two Lynch syndrome patients in co-occurrence with MMR mutations. A statistically non-significant increase in cancer risk was identified in familial CRC and/or other Lynch-associated cancers (1/178 patients vs 2/1121 healthy controls, OR = 3.2, 95%CI: 0.29-35.05, P = 0.348) and in sporadic CRCs (4/1023 patients vs 2/1121 healthy controls, OR = 2.2, 95%CI: 0.40-12.02, P = 0.364).
  
  
  CONCLUSIONS
  We confirm that UNC5C mutations are very rare in familial and sporadic CRCs, but further investigations are needed to justify routine UNC5C testing for diagnostic purposes.
authors.affiliation: Sébastien Küry, Céline Garrec, Fabrice Airaud, Flora Breheret, Virginie Guibert, Cécile Frenard, Stéphane Bezieau, CHU Nantes, Service de Génétique Médicale, 44093 Nantes CEDEX 1, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Küry
authors.affiliation: Sébastien Küry, Céline Garrec, Fabrice Airaud, Flora Breheret, Virginie Guibert, Cécile Frenard, Stéphane Bezieau, CHU Nantes, Service de Génétique Médicale, 44093 Nantes CEDEX 1, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Garrec
authors.affiliation: Sébastien Küry, Céline Garrec, Fabrice Airaud, Flora Breheret, Virginie Guibert, Cécile Frenard, Stéphane Bezieau, CHU Nantes, Service de Génétique Médicale, 44093 Nantes CEDEX 1, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Airaud
authors.affiliation: Sébastien Küry, Céline Garrec, Fabrice Airaud, Flora Breheret, Virginie Guibert, Cécile Frenard, Stéphane Bezieau, CHU Nantes, Service de Génétique Médicale, 44093 Nantes CEDEX 1, France.
authors.forename: Flora
authors.initials: F
authors.lastname: Breheret
authors.affiliation: Sébastien Küry, Céline Garrec, Fabrice Airaud, Flora Breheret, Virginie Guibert, Cécile Frenard, Stéphane Bezieau, CHU Nantes, Service de Génétique Médicale, 44093 Nantes CEDEX 1, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Guibert
authors.affiliation: Sébastien Küry, Céline Garrec, Fabrice Airaud, Flora Breheret, Virginie Guibert, Cécile Frenard, Stéphane Bezieau, CHU Nantes, Service de Génétique Médicale, 44093 Nantes CEDEX 1, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Frenard
authors.affiliation: Sébastien Küry, Céline Garrec, Fabrice Airaud, Flora Breheret, Virginie Guibert, Cécile Frenard, Stéphane Bezieau, CHU Nantes, Service de Génétique Médicale, 44093 Nantes CEDEX 1, France.
authors.forename: Shuo
authors.initials: S
authors.lastname: Jiao
authors.affiliation: Sébastien Küry, Céline Garrec, Fabrice Airaud, Flora Breheret, Virginie Guibert, Cécile Frenard, Stéphane Bezieau, CHU Nantes, Service de Génétique Médicale, 44093 Nantes CEDEX 1, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonneau
authors.affiliation: Sébastien Küry, Céline Garrec, Fabrice Airaud, Flora Breheret, Virginie Guibert, Cécile Frenard, Stéphane Bezieau, CHU Nantes, Service de Génétique Médicale, 44093 Nantes CEDEX 1, France.
authors.forename: Pascaline
authors.initials: P
authors.lastname: Berthet
authors.affiliation: Sébastien Küry, Céline Garrec, Fabrice Airaud, Flora Breheret, Virginie Guibert, Cécile Frenard, Stéphane Bezieau, CHU Nantes, Service de Génétique Médicale, 44093 Nantes CEDEX 1, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Bossard
authors.affiliation: Sébastien Küry, Céline Garrec, Fabrice Airaud, Flora Breheret, Virginie Guibert, Cécile Frenard, Stéphane Bezieau, CHU Nantes, Service de Génétique Médicale, 44093 Nantes CEDEX 1, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Ingster
authors.affiliation: Sébastien Küry, Céline Garrec, Fabrice Airaud, Flora Breheret, Virginie Guibert, Cécile Frenard, Stéphane Bezieau, CHU Nantes, Service de Génétique Médicale, 44093 Nantes CEDEX 1, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Cauchin
authors.affiliation: Sébastien Küry, Céline Garrec, Fabrice Airaud, Flora Breheret, Virginie Guibert, Cécile Frenard, Stéphane Bezieau, CHU Nantes, Service de Génétique Médicale, 44093 Nantes CEDEX 1, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bezieau
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000473:pathology; D005091:Exons; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000075386:Netrin Receptors; D016017:Odds Ratio; D010375:Pedigree; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D000075386:Netrin Receptors; D011956:Receptors, Cell Surface; C115727:UNC5C protein, human
keywords: Association study; Colorectal cancer; Familial study; Genetic predisposition; Low risk; UNC5C