Colorectal Adenomatous Polyposis: Heterogeneity of Susceptibility Gene Mutations and Phenotypes in a Cohort of Italian Patients.

Monica Marabelli, Valeria Molinaro, Raefa Abou Khouzam, Enrico Berrino, Mara Panero, Antonella Balsamo, Tiziana Venesio, Guglielmina Nadia Ranzani

Research output: Contribution to journalArticlepeer-review

Abstract

AIMS: 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). METHODS: 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. RESULTS: 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 x 10(-7)), with APC mutations being associated with an aggressive phenotype (p = 1.279 x 10(-9)). Mean age at diagnosis was lower in FAP/AFAP compared to MAP (p = 3.055 x 10(-4)). Mutation-negative probands showed a mean age at diagnosis that was significantly higher than FAP/AFAP (p = 3.46986 x 10(-7)) and included 45.3% of patients with
Original languageEnglish
Pages (from-to)777-785
Number of pages9
JournalGenetic Testing and Molecular Biomarkers
Volume20
Publication statusPublished - Dec 1 2016

Keywords

  • Adenomatous Polyposis Coli/enzymology/*genetics, Adolescent, Adult, Aged, DNA Glycosylases/genetics, Female, Genetic Association Studies, Genetic Heterogeneity, Genetic Predisposition to Disease, Genotype, Humans, Italy, Male, Middle Aged, Mutation, Phenotype, *FAP-MAP, *genetic predisposition to colorectal polyposis, *genotype-phenotype in colorectal polyposis

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