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DNA repair genes polymorphism and lung cancer risk with the emphasis to sex differences

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Abstract

Polymorphisms in nucleotide and base excision repair genes are associated with the variability in the risk of developing lung cancer. In the present study, we investigated the polymorphisms of following selected DNA repair genes: XPC (Lys939Gln), XPD (Lys751Gln), hOGG1 (Ser326Cys) and XRCC1 (Arg399Gln), and the risks they present towards the development of lung cancer with the emphasis to gender differences within the Slovak population. We analyzed 761 individuals comprising 382 patients with diagnosed lung cancer and 379 healthy controls. Genotypes were determined by polymerase chain reaction/restriction fragment length polymorphism method. We found out statistically significant increased risk for lung cancer development between genders. Female carrying XPC Gln/Gln, XPC Lys/Gln+Gln/Gln and XRCC1 Arg/Gln, XRCC1 Arg/Gln+Gln/Gln genotypes had significantly increased risk of lung cancer corresponding to OR = 2.06; p = 0.04, OR = 1.66; p = 0.04 and OR = 1.62; p = 0.04, OR = 1.69; p = 0.02 respectively. In total, significantly increased risk of developing lung cancer was found in the following combinations of genotypes: XPD Lys/Gln+XPC Lys/Lys (OR = 1.62; p = 0.04), XRCC1 Gln/Gln+hOGG1 Ser/Ser (OR = 2.14; p = 0.02). After stratification for genders, the following combinations of genotype were found to be significant in male: XPD Lys/Gln+XPC Lys/Lys (OR = 1.87; p = 0.03), XRCC1 Arg/Gln+XPC Lys/Lys (OR = 4.52; p = 0.0007), XRCC1 Arg/Gln+XPC Lys/Gln (OR = 5.44; p < 0.0001). In female, different combinations of the following genotypes were found to be significant: XRCC1 Arg/Gln+hOGG1 Ser/Ser (OR = 1.98; p = 0.04), XRCC1 Gln/Gln+hOGG1 Ser/Ser (OR = 3.75; p = 0.02), XRCC1 Arg/Gln+XPC Lys/Gln (OR = 2.40; p = 0.04), XRCC1 Arg/Gln+XPC Gln/Gln (OR = 3.03; p = 0.04). We found out decreased cancer risk in genotype combinations between female patients and healthy controls: XPD Lys/Lys+XPC Lys/Gln (OR = 0.45; p = 0.02), XPD Lys/Gln+XPC Lys/Lys (OR = 0.32; p = 0.005), XPD Lys/Gln+XPC Lys/Gln (OR = 0.48; p = 0.02). Our results did not show any difference between pooled smokers and non-smokers in observed gene polymorphisms in the association to the lung cancer risk. However, gender stratification indicated the possible effect of heterozygous constitution of hOGG1 gene (Ser/Cys) on lung cancer risk in female non-smokers (OR = 0.20; p = 0.01) and heterozygous constitution of XPC gene (Lys/Gln) in male smokers (OR = 2.70; p = 0.01).

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Acknowledgments

This work was supported by the Ministry of Health of the Slovak Republic, Grant No. 2007/48-UK-13 and by Grant APVV–0412-11.

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Authors and Affiliations

  1. Department of Medical Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mala Hora 4, 036 01, Martin, Slovak Republic

    L. Letkova, T. Matakova, M. Sarlinova, M. Krutakova, P. Slovakova & A. Drgova

  2. Department of Medical Biology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mala Hora 4, 036 01, Martin, Slovak Republic

    E. Halasova

  3. Clinic of Occupational Medicine and Toxicology, Jessenius Faculty of Medicine and Martin University Hospital, Kollarova 2, 036 01, Martin, Slovak Republic

    L. Musak

  4. Clinic of Tuberculosis and Respiratory Diseases, Jessenius Faculty of Medicine and Martin University Hospital, Kollarova 2, 036 01, Martin, Slovak Republic

    E. Kavcova

  5. Department of Public Health, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mala Hora 4, 036 01, Martin, Slovak Republic

    V. Jakusova

  6. Clinic of Stomatology and Maxillofacial Surgery, Jessenius Faculty of Medicine and Martin University Hospital, Kollarova 2, 036 01, Martin, Slovak Republic

    M. Janickova

  7. Department of Oncology, Specialized Hospital sv. Svorad Zobor, n.a. Nitra, Klastorska 134, 949 88, Nitra, Slovak Republic

    P. Berzinec

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  1. L. Letkova
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  2. T. Matakova
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Letkova, L., Matakova, T., Musak, L. et al. DNA repair genes polymorphism and lung cancer risk with the emphasis to sex differences. Mol Biol Rep 40, 5261–5273 (2013). https://doi.org/10.1007/s11033-013-2626-z

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