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Nucleotide Excision Repair Capacity and XPC and XPD Gene Polymorphism Modulate Colorectal Cancer Risk.
Mucha, Bartosz; Pytel, Dariusz; Markiewicz, Lukasz; Cuchra, Magda; Szymczak, Izabela; Przybylowska-Sygut, Karolina; Dziki, Adam; Majsterek, Ireneusz; Dziki, Lukasz.
Afiliación
  • Mucha B; Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Lodz, Poland.
  • Pytel D; Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina, United States of America.
  • Markiewicz L; Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Lodz, Poland.
  • Cuchra M; Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Lodz, Poland.
  • Szymczak I; Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Lodz, Poland.
  • Przybylowska-Sygut K; Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Lodz, Poland.
  • Dziki A; Department of General and Colorectal Surgery, Medical University of Lodz, Lodz, Poland.
  • Majsterek I; Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Lodz, Poland. Electronic address: ireneusz.majsterek@umed.lodz.pl.
  • Dziki L; Department of General and Colorectal Surgery, Medical University of Lodz, Lodz, Poland.
Clin Colorectal Cancer ; 17(2): e435-e441, 2018 06.
Article en En | MEDLINE | ID: mdl-29793654
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Proteínas de Unión al ADN / Reparación del ADN / Proteína de la Xerodermia Pigmentosa del Grupo D Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Colorectal Cancer Asunto de la revista: GASTROENTEROLOGIA / NEOPLASIAS Año: 2018 Tipo del documento: Article País de afiliación: Polonia Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Proteínas de Unión al ADN / Reparación del ADN / Proteína de la Xerodermia Pigmentosa del Grupo D Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Colorectal Cancer Asunto de la revista: GASTROENTEROLOGIA / NEOPLASIAS Año: 2018 Tipo del documento: Article País de afiliación: Polonia Pais de publicación: Estados Unidos