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Genetic Polymorphisms of Three DNA-Repair Genes (PRKDC, XPD, XRCC1) are Related to Colorectal Cancer Susceptibility

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Abstract

Although the specific causes of colorectal cancer (CRC) are not known, a robust DNA repair capacity may decrease the risk of this malignancy. DNA repair capacity may be reduced by alterations of genes involved in DNA repair process. This may affect susceptibility to carcinogenesis. It is hypothesized that single nucleotide polymorphisms (SNPs) of several DNA repair genes may be a risk factor for CRC susceptibility and prognosis. Using PCR–RFLP method, we conducted a case-control study to genotype 291 patients with CRC and 140 healthy individuals to determine variants in the PRKDC, XPD and XRCC1 genes. Results showed that the genotypes of XRCC1 c.580C>T polymorphism were associated with the risk of CRC. Compared with CC, CT (odds ratio (OR) = 5.35, P < 0.001) and CT/TT (OR = 4.74, P < 0.001) as well as T allele (OR = 4.95, P < 0.001) were overrepresented among the CRC patients. Variant genotype CC (OR = 2.37; P = 0.042) and C allele of XPD c.2251A>C (OR = 1.37; P = 0.028) polymorphism, enhanced the risk of CRC cases. Compared with GG, positive association was also obtained for all genotypes (GT, TT, GT/TT) of PRKDC rs7003908; 6721G>T polymorphism with CRC. Moreover, T allele of PRKDC demonstrated significant risk for CRC (OR = 5.61; P < 0.001). Besides, significant relevance of the PRKDC rs7003908; 6721G>T variations to smoking as well as XPD c.2251A>C variations to smoking and alcohol consumption in individuals with CRC was observed. Our findings indicated that genetic polymorphisms of PRKDC, XRCC1, XPD genes may influence susceptibility of CRC in the Iranian population.

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ACKNOWLEDGMENTS

This study was financially supported by the 92/7815 grant from Islamic Azad University (Varamin-Pishva Branch) of Iran.

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Authors and Affiliations

  1. Department of Pharmaceutical Biotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Atieh Hashemi

  2. Department of Genetics and Biotechnology, School of Biological Science, Varamin-Pishva Branch, Islamic Azad University, Varamin, Iran

    Fahimeh Baghbani-arani

  3. Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran

    Mona Sadat Larijani

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  1. Atieh Hashemi
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Correspondence to Fahimeh Baghbani-arani.

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Statement of compliance with standards of research involving humans as subjects. All procedures performed in studies involving human participants were approved by the Institutional Ethics Committee and were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants involved in the study.

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Atieh Hashemi, Baghbani-arani, F. & Larijani, M.S. Genetic Polymorphisms of Three DNA-Repair Genes (PRKDC, XPD, XRCC1) are Related to Colorectal Cancer Susceptibility. Cytol. Genet. 54, 363–371 (2020). https://doi.org/10.3103/S0095452720040040

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