Association between single-nucleotide polymorphisms of selected genes involved in the response to DNA damage and risk of colon, head and neck, and breast cancers in a Polish population
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Single-nucleotide polymorphisms in genes involved in DNA-damage-induced responses are reported frequently to be a risk factor in various cancer types. Here we analysed polymorphisms in 5 genes involved in DNA repair (XPD Asp312Asn and Lys751Gln, XRCC1 Arg399Gln, APE1 Asp148Glu, NBS1 Glu185Gln, and XPA G-4A) and in a gene involved in regulation of the cell-cycle (CCND1 A870G). We compared their frequencies in groups of colon, head and neck, and breast cancer patients, and 2 healthy control groups: (1) matched healthy Polish individuals and (2) a NCBI database control group. Highly significant differences in the distribution of genotypes of the APE1, XRCC1 and CCND1 genes were found between colon cancer patients and healthy individuals. The 148Asp APE1 allele and the 399Gln XRCC1 allele apparently increased the risk of colon cancer (OR = 1.9-2.3 and OR = 1.5-2.1, respectively). Additionally, frequencies of XPD genotypes differed between healthy controls and patients with colon or head and neck cancer. Importantly, no differences in the distribution of these polymorphisms were found between healthy controls and breast cancer patients. The data clearly indicate that the risk of colon cancer is associated with single-nucleotide polymorphism in genes involved in base-excision repair and DNA-damage-induced responses.
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P. Widlak, Department of Experimental and Clinical Radiobiology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeze Armii Krajowej 15, Gliwice, Poland