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NER repair system and predisposition to hereditary colorectal cancer: ERCC1 novel mutation in a Tunisian family
Several DNA repair pathways are implicated in heriditary colorectal cancer predisposition. Mismatch Repair (MMR) is the most common repair system of damaged DNA and in maintaining genomic stability. Various other key proteins are involved in this process including Nucleotide Excision Repair (NER) system. In NER system, damaged DNA is excised at the 5' site by the XPF heterodimer (ERCC4)-ERCC1. According to published studies, genetic variants on ERCC1 may influence colorectal cancer susceptibility. Variants of NER genes association with colorectal cancer (CRC) risk were inconclusive.
The index case was operated at the age of 5 years old for a right kidney tumor (right nephrectomy), then at 21 years old for colon transverse adenocarcinoma (T3N0Mx). At the age of 23 years old he had a small intestine well differentiated adenocarcinoma (T2NxMx). At 25 years old he developed a duodenal adenocarcinoma. The index case had two sisters who died of a colorectal cancer at the age of 18 and 20 years old and a half-sister who had colorectal cancer at the age of 35 years.
Genomic DNA screening, by targeted DNA repair genes panel, revealed an ERCC1 stopgain mutation (exon 8:c.875G>A:p.W292X), confirmed by Sanger sequencing. This variation was suspected to be a causal mutation associated to early colorectal cancer onset in this family.
This is the first Tunisian study which highlights that variant in the xeroderma pigmentosum genes family (XP) could play an important role in early colorectal cancer predisposition. Only a few studies have examined the contribution of SNPs in NER pathway genes to early CRC risk.
The authors.
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All authors have declared no conflicts of interest.
