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Association of DCC, MLH1, GSTT1, GSTM1, and TP53 gene polymorphisms with colorectal cancer in Kazakhstan

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Tumor Biology

Abstract

This study presents the first results of a molecular-genetic study of colorectal cancer (CRC) in Kazakhstan. Blood samples were collected from patients diagnosed with rectal or colon cancer (249 individuals) as well as a control cohort of healthy volunteers (245 individuals), taking into account the age, gender, ethnicity, and smoking habits of the CRC patients. Combined analysis of data obtained from individuals of either Kazakh or Russian decent showed a significant association with increased CRC risk in the following genotypes: DCC (32008376G/G and G/A versus A/A; OR = 3.45, 95 % confidence interval (95 %CI) = 1.75–6.81, χ 2 = 14.07, p < 0.0002), MLH1 (-93G/G versus G/A and A/A; OR = 1.45, 95 %CI = 1.02–2.07, χ 2 = 4.21, p < 0.04), TP53 (Pro72Pro; OR = 3.80, 95 %CI = 2.46–5.88, χ 2 = 61.27, p < 0.0001), combination GSTT1 deletions with heterozygotes versus normal homozygotes (OR = 1.43, 95 %CI = 1.00–2.04, χ 2 = 3.90, p < 0.05), and GSTM1 deletions (OR = 1.83, 95 %CI = 1.28–2.63, χ 2 = 11.04, p < .001). Analysis for ethnicity and smoking for each of the investigated polymorphisms showed that some genotypes can have a predictive value for susceptibility to CRC, at least those that demonstrate statistically significant ORs either for the combined mixed population of Kazakhstan or for both main ethnic groups separately (Kazakhs and Russians): TP53 Pro72Pro homozygous (for Kazakh—OR = 3.40, 95 %CI = 1.63–7.06, χ 2 = 11.35, p < 0.003; for Russian—OR = 4.69, 95 %CI = 2.53–8.66, χ 2 = 53.19, p < 0.0001) and GSTM1 deletions (for Kazakh—OR = 2.30, 95 %CI = 1.21–4.40, χ 2 = 8.42, p < 0.01; for Russian—OR = 1.64, 95 %CI = 1.01–2.66, χ 2 = 7.82, p < 0.02).

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Acknowledgments

This work was supported by grant N.0067/GF of the Committee of Science, Ministry of Education and Science of Republic of Kazakhstan. MIP was funded by grants from the ICGEB, the Medical Research Council, and the University of Cape Town.

We would like to express our gratitude to the doctors of Almaty Oncology Centre for the help in collecting biosamples and histological testing. Very special thanks are expressed to the rector of the Asfendiyarov Kazakh National Medical University Aikan Akanov and Head of Oncological Department Bakhyt Kh. Khaidarov who managed the research and did ethical attestation.

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Authors and Affiliations

  1. Laboratory of Molecular Genetics, Institute of General Genetics and Cytology, Al-Farabi Ave., 93, Almaty, Kazakhstan, 050060

    Leyla Djansugurova, Gulnur Zhunussova, Elmira Khussainova & Olzhas Iksan

  2. Almaty Oncology Centre, Almaty, Kazakhstan, 050060

    Georgiy Afonin & Dilyara Kaidarova

  3. International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component and Medical Biochemistry/IDM, UCT, Observatory, University of Cape Town, Cape Town, South Africa

    Gulnur Zhunussova & M. Iqbal Parker

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  1. Leyla Djansugurova
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  2. Gulnur Zhunussova
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Correspondence to Leyla Djansugurova.

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Djansugurova, L., Zhunussova, G., Khussainova, E. et al. Association of DCC, MLH1, GSTT1, GSTM1, and TP53 gene polymorphisms with colorectal cancer in Kazakhstan. Tumor Biol. 36, 279–289 (2015). https://doi.org/10.1007/s13277-014-2641-2

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