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Polymorphisms of the GSTM1, GSTT1, and CYP2D6 xenobiotic biotransformation genes, which are possible risk markers of cancer in populations of indigenous ethnic groups and Russians of North Siberia

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Russian Journal of Genetics: Applied Research

Abstract

The CYP2D6, GSTM1, and GSTT1 xenobiotic biotransformation genes are involved in processes of carcinogenesis in humans due to the presence of mutant variants that decrease or block the expression of genes. Since the middle of the 20th century, there has been an extensive increase in cancer morbidity in human populations, including indigenous ethnic groups of Siberia. The problem of ethnic differences in susceptibility to cancer is still pressing. The study of polymorphisms of the CYP2D6 (CYP2D6*3 and CYP2D6*4 alleles), GSTM1, and GSTT1 (GSTM1 0/0 and GSTT1 0/0 “null” genotypes) genes (which are considered as genetic markers of the risk of cancer) was conducted for the first time in practically healthy representatives of the Samoyedic ethnic groups (Selkups, Forest Nenets, and Nganasans) and Russians from Siberia. A significant variability in the CYP2D6*4 and GSTM1 0/0 frequency distribution in northern populations was detected. At the same time, there are no significant differences in frequencies of the CYP2D6*3 and GSTT1 0/0 variants among indigenous populations of the Selkups, Forest Nenets, and Nganasans. In the CYP2D6*4 allele frequencies, indigenous ethnic groups are intermediate between Russians of Siberia and Mongolians of China. However, frequencies of the null GSTM1 0/0 and GSTT1 0/0 genotypes in indigenous ethnic groups are significantly lower than in populations of Russians of Siberia and Mongoloids of China (p < 0.05). Generally, according to all four studied polymorphic variants, it is possible to predict a decreased risk of cancer in indigenous Samoyedic ethnic groups, as compared with Russians of Siberia. The Forest Nenets population, with an increased frequency of the GSTM1 0/0 genotypes, is an exception; this can be caused by the originality of their marriage structure and increased inbreeding coefficient. The results we obtained can also be important in predicting the probability of complications and a positive response to drugs that are metabolized by the GSTM1, GSTT1, and CYP2D6 enzymes.

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Authors and Affiliations

  1. Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia

    R. P. Korchagina, L. P. Osipova & N. A. Vavilova

  2. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia

    N. A. Ermolenko, E. N. Voronina & M. L. Filipenko

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  1. R. P. Korchagina
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  2. L. P. Osipova
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Original Russian Text © R.P. Korchagina, L.P. Osipova, N.A. Vavilova, N.A. Ermolenko, E.N. Voronina, M.L. Filipenko, 2011, published in Vavilovskii Zhurnal Genetiki i Selektsii, 2011, Vol. 15, No. 3, pp. 448–461.

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Korchagina, R.P., Osipova, L.P., Vavilova, N.A. et al. Polymorphisms of the GSTM1, GSTT1, and CYP2D6 xenobiotic biotransformation genes, which are possible risk markers of cancer in populations of indigenous ethnic groups and Russians of North Siberia. Russ J Genet Appl Res 2, 7–17 (2012). https://doi.org/10.1134/S2079059712010091

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