Nucleotide Excision Repair Capacity andXPCandXPDGene Polymorphism Modulate Colorectal Cancer Risk

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Abstract

Background

Colorectal cancer (CRC) is leading malignant tumors to occur mainly in industrialized countries, where it exhibits one of the highest mortality rates. Up to 80% of all CRCs characterize a chromosomal instability (CIN) phenotype. The main challenge faced by scientist is to reveal the mechanism of CIN development. An often proposed model is defects in DNA repair in terms of efficiency and genetic variations that modulate the response to stimuli from the environment. The objectives of this research were to determine whether nucleotide excision repair (NER) might affect CRC risk.

Materials and Methods

The first part of the study concerns NER efficiency. In the second part we selected 2 common single nucleotide polymorphisms within genes involved in NER (Xeroderma pigmentosum group C (XPC) Lys939Gln, Xeroderma pigmentosum group D (XPD) Lys751Gln) to determine the relation between them and CRC risk. The restriction fragment length polymorphism-polymerase chain reaction method was used for genotyping of 221 CRC patients vs. 270 cancer-free individuals. The isotopic labeling in vitro assay was used to evaluate NER capacity in lymphocytes and tissue protein extracts.

Results

We observed a significantly decreased level of NER capacity (P = .025) in lymphocytes delivered from CRC patients compared with healthy ones. Polymorphism screening points to higher CRC risk for the Gln939Gln genotype (P = .02) and Gln allele (P = .002) of the XPC gene.

Conclusion

Taken together, our findings suggest a potential role for NER in CRC.

Micro-Abstract

Chromosomal instability is a dominant molecular feature in sporadic colorectal cancer which may occure as failure to repair DNA damage. Nucleotide excision repair (NER) is one of the leading DNA repair mechanism which has been considered in many studies to play vital role in carcinogenesis. The findings of this study suggest decreased NER activity in colorectal cancer patients and significance of genetic variation withing NER genes.

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