title: Colorectal Adenomatous Polyposis: Heterogeneity of Susceptibility Gene Mutations and Phenotypes in a Cohort of Italian Patients.
abstract: Colorectal adenomatous polyposis entailing cancer predisposition is caused by constitutional mutations in different genes. APC is associated with the familial adenomatous polyposis (FAP/AFAP) and MUTYH with the MUTYH-associated polyposis (MAP), while POLE and POLD1 mutations cause the polymerase proofreading-associated polyposis (PPAP).
  
  
  
  We screened for mutations in patients with multiple adenomas/FAP: 121 patients were analyzed for APC and MUTYH mutations, and 36 patients were also evaluated for POLE and POLD1 gene mutations.
  
  
  
  We found 20 FAP/AFAP, 15 MAP, and no PPAP subjects: pathogenic mutations proved to be heterogeneous, and included 5 APC and 1 MUTYH novel mutations. The mutation detection rate was significantly different between patients with 5-100 polyps and those with >100 polyps (p = 8.154 × 10-7), with APC mutations being associated with an aggressive phenotype (p = 1.279 × 10-9). Mean age at diagnosis was lower in FAP/AFAP compared to MAP (p = 3.055 × 10-4). Mutation-negative probands showed a mean age at diagnosis that was significantly higher than FAP/AFAP (p = 3.46986 × 10-7) and included 45.3% of patients with <30 polyps and 70.9% of patients with no family history.
  
  
  
  This study enlarges the APC and MUTYH mutational spectra, and also evaluated variants of uncertain significance, including the MUTYH p.Gln338His mutation. Moreover this study underscores the phenotypic heterogeneity and genotype-phenotype correlations in a cohort of Italian patients.
authors.affiliation: 1 Department of Biology and Biotechnology, University of Pavia , Pavia, Italy .
authors.forename: Monica
authors.initials: M
authors.lastname: Marabelli
authors.affiliation: 1 Department of Biology and Biotechnology, University of Pavia , Pavia, Italy .
authors.forename: Valeria
authors.initials: V
authors.lastname: Molinaro
authors.affiliation: 1 Department of Biology and Biotechnology, University of Pavia , Pavia, Italy .
authors.forename: Raefa
authors.initials: R
authors.lastname: Abou Khouzam
authors.affiliation: 2 Candiolo Cancer Institute , FPO-IRCCS, Torino, Italy .
authors.forename: Enrico
authors.initials: E
authors.lastname: Berrino
authors.affiliation: 2 Candiolo Cancer Institute , FPO-IRCCS, Torino, Italy .
authors.forename: Mara
authors.initials: M
authors.lastname: Panero
authors.affiliation: 2 Candiolo Cancer Institute , FPO-IRCCS, Torino, Italy .
authors.forename: Antonella
authors.initials: A
authors.lastname: Balsamo
authors.affiliation: 2 Candiolo Cancer Institute , FPO-IRCCS, Torino, Italy .
authors.forename: Tiziana
authors.initials: T
authors.lastname: Venesio
authors.affiliation: 1 Department of Biology and Biotechnology, University of Pavia , Pavia, Italy .
authors.forename: Guglielmina Nadia
authors.initials: GN
authors.lastname: Ranzani
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000201:enzymology / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D045647:DNA Glycosylases / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype
chemical_list: D045647:DNA Glycosylases
keywords: FAP-MAP; genetic predisposition to colorectal polyposis; genotype-phenotype in colorectal polyposis