POLD1 and POLE Gene Mutations in Jewish Cohorts of Early-Onset Colorectal Cancer and of Multiple Colorectal Adenomas

BACKGROUND: Germline mutations in the DNA polymerase genes POLD1 and POLE confer high risk for multiple colorectal adenomas and colorectal cancer. However, prevalence and the clinical phenotype of mutation carriers are still not fully characterized. OBJECTIVE: The purpose of this study was to assess the prevalence of germline mutations and to describe the genotype-phenotype correlation in POLD1 and POLE genes in Jewish subjects with multiple colorectal adenomas and/or early-onset mismatch repair proficient colorectal cancers. DESIGN: This study is a comparison of genetic and clinical data from affected and control groups. SETTINGS: The study was conducted at a high-volume tertiary referral center. PATIENTS: The study cohort included 132 subjects: 68 with multiple colorectal adenomas and 64 with early-onset mismatch repair proficient colorectal cancers. The control group included 5685 individuals having no colorectal cancer or colorectal adenomas. MAIN OUTCOME MEASURES: Study and control subjects were tested for POLD1 and POLE mutations and a clinical correlation was assessed. RESULTS: Eleven of the 132 study subjects (8.3%) carried either a POLD1 or a POLE mutation: 7 of 68 (10.3%) subjects with multiple colorectal adenomas and 4 of 64 (6.2%) subjects with early-onset mismatch repair proficient colorectal cancer. Three mutations were detected, showing statistical significance in frequency between study and control groups (p

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