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Polymorphisms in DNA repair genes in lung cancer patients living in a coal-mining region

Minina, Varvara I.a,,b; Bakanova, Marina L.a; Soboleva, Olga A.a; Ryzhkova, Anastasia V.a; Titov, Ruslan A.a; Savchenko, Yana A.a; Sinitsky, Maxim Yu.a,,c; Voronina, Elena N.e,,f; Titov, Victor A.a,,d; Glushkov, Andrey N.a

European Journal of Cancer Prevention: November 2019 - Volume 28 - Issue 6 - p 522–528
doi: 10.1097/CEJ.0000000000000504
Research Papers: Lung Cancer
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Air pollutants and ionizing radiation are well-known carcinogens involved in the pathogenesis of lung cancer, and residents of coal-mining regions are exposed routinely to these agents. Polymorphisms in DNA repair genes may be associated with an increased risk of malignant transformation. We investigated associations between the risk of lung cancer in residents of the coal-mining region and polymorphisms in the genes APEX1 (rs1130409), hOGG1 (rs1052133), XRCC1 (rs25489, rs25487), XRCC2 (rs3218536), XRCC3 (rs861539), ADPRT/PARP1 (rs1136410), XPD/ERCC2 (rs13181), XPG/ERCC5 (rs17655), XPC (rs2228001), ATM (rs1801516), and NBS1 (rs1805794). Three hundred and forty residents of the Kemerovo Region (a coal-mining region of western Siberia) were lung cancer patients exposed to air pollutants and ionizing radiation (case) and 335 were healthy donors (control). Genotyping was performed by real-time PCR and allele-specific PCR. We discovered that polymorphisms in the XPD gene in men [log-additive model: odds ratio (OR) = 1.64, 95% confidence interval (CI): 1.17–2.31], the ATM gene in women and nonsmokers (codominant model: OR = 0.11, 95% CI: 0.02–0.49 and OR = 0.25, 95% CI: 0.08–0.72, respectively), the APEX1 gene for smokers (recessive model: OR = 2.55, 95% CI: 1.34–4.85), and the NBS1 gene for those who work in the coal industry (overdominant model: OR = 0.40, 95% CI: 0.21–0.75) are associated with an increased risk of lung cancer. Using the multifactor dimensionality reduction method, we found a model of gene–gene interactions associated with the risk of lung cancer: NBS1 (rs1805794)–XRCC1 (rs25487)–hOGG1 (rs1052133)–XPG (rs17655). These results indicate an association between combinations of polymorphisms in the studied genes and the risk of lung cancer in residents of a coal-mining region.

aThe Federal Research Center of Coal and Coal Chemistry of SB RAS

bDepartment of Genetics, Biology Faculty, Kemerovo State University

cLaboratory of Genome Medicine, Research Institute for Complex Issues of Cardiovascular Diseases

dKemerovo Regional Oncology Center, Kemerovo

eInstitute of Chemical Biology and Fundamental Medicine of SB RAS

fNovosibirsk State University, Novosibirsk, Russia

Received 10 August 2018 Accepted 19 January 2019

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*Correspondence to Maxim Y. Sinitsky, PhD, Laboratory of Genome Medicine, Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Blvd 6, 650002 Kemerovo, Russia Tel: + 7 3842 644 527; fax: + 7 3842 643 410; email: sinitsky.maxim@gmail.com

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