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Tumor Biology

, Volume 36, Issue 1, pp 279–289 | Cite as

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

  • Leyla Djansugurova
  • Gulnur Zhunussova
  • Elmira Khussainova
  • Olzhas Iksan
  • Georgiy Afonin
  • Dilyara Kaidarova
  • M. Iqbal Parker
Research Article

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).

Keywords

Single nucleotide polymorphisms Tumor suppressor genes DNA mismatch repair genes GST deletions 

Notes

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.

Conflicts of interest

None

Supplementary material

13277_2014_2641_MOESM1_ESM.docx (53 kb)
ESM 1 (DOCX 52 kb)

References

  1. 1.
    Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet. 2014;383:1490–502.CrossRefPubMedGoogle Scholar
  2. 2.
    Sjöblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, et al. The consensus coding sequences of human breast and colorectal cancers. Science. 2006;314:268–74.CrossRefPubMedGoogle Scholar
  3. 3.
    Goode EL, Ulrich CM, Potter JD. Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev. 2001;11:1513–30.Google Scholar
  4. 4.
    Deschoolmeester V, Baay M, Specenier P, Lardon F, Vermorken JB. A review of the most promising biomarkers in colorectal cancer: one step closer to targeted therapy. Oncologist. 2010;15:699–731.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Economopoulos KP, Sergentanis TN. GSTM1, GSTT1, GSTP1, GSTA1 and colorectal cancer risk: a comprehensive meta-analysis. Eur J Cancer. 2010;46:1617–31.CrossRefPubMedGoogle Scholar
  6. 6.
    Migliore L, Migheli F, Spisni R, Coppede F. Genetics, cytogenetics, and epygenetics of colorectal cancer. J Biomed Biotech. 2011. doi: 10.1155/2011/792362.Google Scholar
  7. 7.
    Taflin H, Wettergren Y, Odin E, Carlsson G, Derwinger K. Folate levels and polymorphisms in the genes MTHFR, MTR, and TS in colorectal cancer. Clin Med Insights Oncol. 2014;8:15–20. doi: 10.4137/CMO.S12701.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Peng Q, Yang S, Lao X, Tang W, Chen Z, Lai H, et al. Meta-analysis of the association between COX-2 polymorphisms and risk of colorectal cancer based on case–control studies. PLoS ONE. 2014. doi: 10.1371/journal.pone.0094790.Google Scholar
  9. 9.
    Keino-Masu K, Masu M, Hinck L, Leonardo ED, Chan SS, Culotti JG, et al. Deleted in colorectal cancer (DCC) encodes a netrin receptor. Cell. 1996;87:175–85.CrossRefPubMedGoogle Scholar
  10. 10.
    Akkiprik M, Ataizi-Celikel C, Düúünceli F, Sönmez O, Gulluoglu BM, Sav A, et al. Clinical significance of p53, K-ras and DCC gene alterations in the stage I-II colorectal cancers. J Gastrointest and Liver Dis. 2007;16:11–7.Google Scholar
  11. 11.
    Toma M, Stavarachi M, Cimponeriu D, Apostol P, Cojocaru M, Beluşică L, et al. P53 and DCC polymorphisms and the risk for colorectal cancer in Romanian patients—a preliminary study. J Analele Universităţii din Oradea, Fascicula Biol. 2009;16:162–5.Google Scholar
  12. 12.
    Naccarati A, Polakova V, Pardini B, Vodickova L, Hemminki K, Kumar R, et al. Mutations and polymorphisms in TP53 gene—an overview on the role in colorectal cancer. Mutagenesis. 2012;27:211–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Raptis S, Mrkonjic M, Green RC, Pethe VV, Monga N, Chan YM, et al. MLH1–93G>A promoter polymorphism and the risk of microsatellite-unstable colorectal cancer. J Natl Cancer Inst. 2007;99:463–74.CrossRefPubMedGoogle Scholar
  14. 14.
    Allan JM, Shorto J, Adlard J, Bury J, Coggins R, George R, et al. MLH1–93G>A promoter polymorphism and risk of mismatch repair deficient colorectal cancer. Int J Cancer. 2008;123:2456–9. doi: 10.1002/ijc.23770.CrossRefPubMedGoogle Scholar
  15. 15.
    Nizam ZM, Abdul Aziz AA, Kaur G, Abu Hassan MR, Mohd Sidek AS, Yeh LY, et al. Contribution of the MLH1–93G>A promoter polymorphism in modulating susceptibility risk in Malaysian colorectal cancer patients. Asian Pac J Cancer Prev. 2013;14:619–24.CrossRefPubMedGoogle Scholar
  16. 16.
    Djansugurova LB, Perfilyeva AV, Zhunusova GS, Djantaeva KB, Iksan OA, Khussainova EM. The determination of genetic markers of age-related cancer pathologies in populations from Кazakhstan. Front Genet. 2013. doi: 10.3389/fgene.2013.00070.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Abbas A, Delvinquiere K, Lechevrel M, Lebalilly P, Gauduchon P, Launoy G, et al. GSTM1, GSTT1, GSTP1 and CYP1A1 genetic polymorphisms and susceptibility to esophageal cancer in French population: different pattern of squamous cell carcinoma and adenocarcinoma. World J Gastroenterol. 2004;10:3389–93.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Khan NP, Pandith AA, Hussain MU, Yousuf A, Khan MS, Siddiqi MA, et al. Loss of heterozygosity (LOH) of deleted in colorectal cancer (DCC) gene and predisposition to colorectal cancer: significant association in colorectal cancer patients of Kashmir. J Cancer Res Expt Oncol. 2011;3:88–94.Google Scholar
  19. 19.
    Rai R, Sharma KL, Tiwari S, Misra S, Kumar A, Mittal B. DCC (deleted in colorectal carcinoma) gene variants confer increased susceptibility to gallbladder cancer. Gene. 2013;518:303–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Park SH, Lee GY, Jeon HS, Lee SJ, Kim KM, Jang SS, et al. 93G>A polymorphism of hMLH1 and risk of primary lung cancer. Int J Cancer. 2004;112:678–82.CrossRefPubMedGoogle Scholar
  21. 21.
    Lu XM, Zhang YM, Lin RY, Liang XH, Wang X, Zhang Y, et al. p53 polymorphism in human papillomavirus-associated Kazakh’s esophageal cancer in Xinjiang, China. World J Gastroenterol. 2004;10:2775–8.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    D’Errico A, Malats N, Vineis P, Boffetta P. Review of studies of selected metabolic polymorphisms and cancer. IARC Sci Publ. 1999;148:323–93.Google Scholar
  23. 23.
    Ketterer B, Taylor J, Meyer D, Pemble S, Coles B, ChuLin X, et al. Structure and functions of glutathione S-transferases. CRC Press Boca Raton Florida. 2007;15:15–27.Google Scholar
  24. 24.
    Gao LB, Pan XM, Li LJ, Liang WB, Bai P, Rao L, et al. Null genotypes of GSTM1 and GSTT1 contribute to risk of cervical neoplasia: an evidence-based meta-analysis. PLoS ONE. 2011;6:1–7. doi: 10.1371/journal.pone.0020157.Google Scholar
  25. 25.
    Malik MA, Gupta A, Zargar SA, Mittal B. Role of genetic variants of deleted in colorectal carcinoma (DCC) polymorphisms and esophageal and gastric cancers risk in Kashmir Valley and meta-analysis. Tumor Biol. 2013;34:3049–57. doi: 10.1007/s13277-013-0870-4.CrossRefGoogle Scholar
  26. 26.
    Francisco G, Menezes PR, Eluf-Neto J, Chammas R. Arg72Pro TP53 polymorphism and cancer susceptibility: a comprehensive meta-analysis of 302 case–control studies. Int J Cancer. 2010;129:920–30.CrossRefPubMedGoogle Scholar
  27. 27.
    Dumont P, Leu JI, Della Pietra 3rd AC, George DL, Murphy M. The codon 72 polymorphic variants of TP53 have markedly different apoptotic potential. Nat Genet. 2003;33:357–65.CrossRefPubMedGoogle Scholar
  28. 28.
    Sullivan A, Syed N, Gasco M, Bergamaschi D, Trigiante G, Attard M, et al. Polymorphism in wild-type TP53 modulates response to chemotherapy in vitro and in vivo. Oncogene. 2004;23:3328–37.CrossRefPubMedGoogle Scholar
  29. 29.
    Storey A, Thomas M, Kalita A, Harwood C, Gardiol D, Mantovani F, et al. Role of a p53 polymorphism in the development of human papillomavirus-associated cancer. Nature. 1998;393:229–34.CrossRefPubMedGoogle Scholar
  30. 30.
    Wang JJ, Zheng Y, Sun L, Wang L, Yu PB, Dong JH, et al. TP53 codon 72 polymorphism and colorectal cancer susceptibility: a meta-analysis. Mol Biol Rep. 2011;388:4847–53. doi: 10.1007/s11033-010-0619-8.CrossRefGoogle Scholar
  31. 31.
    Goodman JE, Mechanic LE, Luke BT, Ambs S, Chanock S, Harris CC. Exploring SNP-SNP interactions and colon cancer risk using polymorphism interaction analysis. Int J Cancer. 2006;118:1790–7.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Perfumo C, Bonelli L, Menichini P, Inga A, Gismondi V, Ciferri E, et al. Increased risk of colorectal adenomas in Italian subjects carrying the p53 PIN3 A2-Pro72 haplotype. Digestion. 2006;74:228–35.CrossRefPubMedGoogle Scholar
  33. 33.
    Zhu ZZ, Wang AZ, Jia HR, Jin XX, He XL, Hou LF, et al. Association of the TP53 codon 72 polymorphism with colorectal cancer in a Chinese population. Jpn J Clin Oncol. 2007;37:385–90.CrossRefPubMedGoogle Scholar
  34. 34.
    Dastjerdi MN, Salehi M, Mohajeri MR. Evidence for an association of TP53 codon 72 polymorphism with sporadic colorectal cancer risk in Isfahan. J of Res in Med Sci. 2008;13:317–23.Google Scholar
  35. 35.
    Cao Z, Song JH, Park YK, Maeng EJ, Nam SW, Lee JY, et al. The p53 codon 72 polymorphism and susceptibility to colorectal cancer in Korean patients. Neoplasma. 2009;56:114–8.CrossRefPubMedGoogle Scholar
  36. 36.
    Sameer AS, Shah ZA, Syeed N, Banday MZ, Bashir SM, Bhat BA, et al. TP53 Pro47Ser and Arg72Pro polymorphisms and colorectal cancer predisposition in an ethnic Kashmiri population. Genet Mol Res. 2010;9:651–60.CrossRefPubMedGoogle Scholar
  37. 37.
    Rajagopal R, Deakin M, Fawole AS, Elder JB, Elder J, Smith V, et al. Glutathione S-transferase T1 polymorphisms are associated with outcome in colorectal cancer. Carcinogenesis. 2005;26:2157–63. doi: 10.1093/carcin/bgi195.CrossRefPubMedGoogle Scholar
  38. 38.
    Csejtei A, Tibold A, Varga Z, Koltai K, Ember A, Orsos Z, et al. GSTM, GSTT and p53 polymorphisms as modifiers of clinical outcome in colorectal cancer. Anticancer Res. 2008;28:1917–22.PubMedGoogle Scholar
  39. 39.
    Katoh T, Nagata N, Kuroda Y, Itoh H, Kawahara A, Kuroki N, et al. Glutathione S-transferase Ml (GSTM1) and Tl (GSTT1) genetic polymorphism and susceptibility to gastric and colorectal adenocarcinoma. Carcinogenesis. 1996;17:1855–9.CrossRefPubMedGoogle Scholar
  40. 40.
    Moore LE, Huang WY, Chatterjee N, Gunter M, Chanock S, Yeager M, et al. GSTM1, GSTT1, and GSTP1 polymorphisms and risk of advanced colorectal adenoma. Cancer Epidemiol Biomarkers Prev. 2005;14:1823–7.CrossRefPubMedGoogle Scholar
  41. 41.
    Huang K, Sandler RS, Millikan RC, Schroeder JC, North KE, Hu J. GSTM1 and GSTT1 polymorphisms, cigarette smoking, and risk of colon cancer: a population-based case–control study in North Carolina (United States). Cancer Causes Control. 2006;17:385–94.CrossRefPubMedGoogle Scholar
  42. 42.
    Gertig DM, Stampfer M, Haiman C, Hennekens CH, Kelsey K, Hunter DJ. Glutathione S-transferase GSTM1 and GSTT1 polymorphisms and colorectal cancer risk: a prospective study. Cancer Epidemiol Biomarkers Prev. 1998;7:1001–5.PubMedGoogle Scholar
  43. 43.
    Little J, Sharp L, Masson LF, Brockton NT, Cotton SC, Haites NE, et al. Colorectal cancer and genetic polymorphisms of CYP1A1, GSTM1 and GSTT1: a case–control study in the Grampian region of Scotland. Int J Cancer. 2006;119:2155–64.CrossRefPubMedGoogle Scholar
  44. 44.
    Ye Z, Parry JM. A meta-analysis of 20 case–control studies of the glutathione S-transferase M1 (GSTM1) status and colorectal cancer risk. Med Sci Monit. 2003;9:SR83–91.PubMedGoogle Scholar
  45. 45.
    Pan XM, Yang WZ, Xu GH, Bai P, Qin HJ, Zhang LS, et al. The association between MLH1–93G>A polymorphism of DNA mismatch repair and cancer susceptibility: a meta-analysis. Mutagenesis. 2011;26:667–73. doi: 10.1093/mutage/ger032.CrossRefPubMedGoogle Scholar
  46. 46.
    Perera S, Mrkonjic M, Rawson JB, Bapat B. Functional effects of the MLH1–93G>A polymorphism on MLH1/EPM2AIP1 promoter activity. Oncol Rep. 2011;25:809–15.PubMedGoogle Scholar
  47. 47.
    Chen H, Taylor NP, Sotamaa KM, Mutch DG, Powell MA, Schmidt AP, et al. Evidence for heritable predisposition to epigenetic silencing of MLH1. Int J Cancer. 2007;120:1684–8.CrossRefPubMedGoogle Scholar
  48. 48.
    Koessler T, Oestergaard MZ, Song H, Tyrer J, Perkins B, Dunning AM, et al. Common variants in mismatch repair genes and risk of colorectal cancer. Gut. 2008;57:1097–101.CrossRefPubMedGoogle Scholar
  49. 49.
    Campbell PT, Curtin K, Ulrich CM, Samowitz WS, Bigler J, Velicer CM, et al. Mismatch repair polymorphisms and risk of colon cancer, tumour microsatellite instability and interactions with lifestyle factors. Gut. 2009;58:661–7.CrossRefPubMedGoogle Scholar
  50. 50.
    Muniz-Mendoza R, Ayala-Madrigal ML, Partida-Pérez M, Peregrina-Sandoval J, Leal-Ugarte E, Macías-Gómez N, et al. MLH1 and XRCC1 polymorphisms in Mexican patients with colorectal cancer. Genet Mol Res. 2012;11:2315–20. doi: 10.4238/2012.June.27.6.CrossRefPubMedGoogle Scholar
  51. 51.
    Jha R, Gaur P, Sharma SC, Das SN. Single nucleotide polymorphism in hMLH1 promoter and risk of tobacco-related oral carcinoma in high-risk Asian Indians. Gene. 2013;526:223–7.CrossRefPubMedGoogle Scholar
  52. 52.
    Lee KM, Choi JY, Kang C, Kang CP, Park SK, Cho H, et al. Genetic polymorphisms of selected DNA repair genes, estrogen and progesterone receptor status, and breast cancer risk. Clin Cancer Res. 2005;11:4620–6.CrossRefPubMedGoogle Scholar
  53. 53.
    Fearon ER, Cho KR, Nigro JM, Kern SE, Simons JW, Ruppert JM, et al. Identification of a chromosome 18q gene that is altered in colorectal cancers. Science. 1990;247:49–56.CrossRefPubMedGoogle Scholar
  54. 54.
    Fearon ER. DCC: is there a connection between tumorigenesis and cell guidance molecules? Biochim Biophys Acta. 1996;9:17–23.Google Scholar
  55. 55.
    Shibata D, Reale MA, Lavin P, Silverman M, Fearon ER, Steele Jr G, et al. The DCC protein and prognosis in colorectal cancer. N Engl J Med. 1996;335:1727–32.CrossRefPubMedGoogle Scholar
  56. 56.
    Sun XF, Rütten S, Zhang H, Nordenskjöld B. Expression of the deleted in colorectal cancer gene is related to prognosis in DNA diploid and low proliferative colorectal adenocarcinoma. J Clin Oncol. 1999;17:1745–50.CrossRefPubMedGoogle Scholar
  57. 57.
    Zhang H, Arbman G, Sun XF. Codon 201 polymorphism of DCC gene is a prognostic factor in patients with colorectal cancer. Cancer Detect Prev. 2003;27:216–21.CrossRefPubMedGoogle Scholar
  58. 58.
    Starinsky S, Figer A, Ben-Asher E, Geva R, Flex D, Fidder HH, et al. Genotype phenotype correlations in Israeli colorectal cancer patients. Int J Cancer. 2005;114:58–73.CrossRefPubMedGoogle Scholar
  59. 59.
    Cha PC, Zembutsu H, Takahashi A, Kubo M, Kamatani N, Nakamura YJ. A genome-wide association study identifies SNP in DCC is associated with gallbladder cancer in the Japanese population. Hum Genet. 2012;57:235–7.CrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Leyla Djansugurova
    • 1
  • Gulnur Zhunussova
    • 1
    • 3
  • Elmira Khussainova
    • 1
  • Olzhas Iksan
    • 1
  • Georgiy Afonin
    • 2
  • Dilyara Kaidarova
    • 2
  • M. Iqbal Parker
    • 3
  1. 1.Laboratory of Molecular GeneticsInstitute of General Genetics and CytologyAlmatyKazakhstan
  2. 2.Almaty Oncology CentreAlmatyKazakhstan
  3. 3.International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component and Medical Biochemistry/IDM, UCT, ObservatoryUniversity of Cape TownCape TownSouth Africa

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