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The Role of O6-methylguanine-DNA Methyltransferase Polymorphisms in Prostate Cancer Susceptibility: a Meta-Analysis

  • Wei Zhang
  • Mingkai Liu
  • Yue Li
  • Shichao Song
  • Kai Li
  • Yongliang MaEmail author
Original Article
  • 15 Downloads

Abstract

To assess the associations between O6-methylguanine-DNA methyltransferase(MGMT) polymorphisms and prostate cancer risk. We retrieved PubMed, Cochrane Library and Embase electronic database to search for all eligible studies published from Jan 1, 1970 to Sep 31, 2017 to conduct a Meta-analysis. we identified 11 independent studies in 5 eligible reports, including 5143 cases and 8118 controls. The data suggested that rs12917 was associated with higher PCa risk under the contrast of TT vs CC and recessive model in overall population (TT vs CC: OR = 1.599, 95%CI: 1.007–2.539, P = 0.047; TT vs CC + CT: OR = 1.627, 95%CI: 1.026–2.580, P = 0.038). In subgroup analyses stratified by ethnicity, the remarkable association with higher PCa risk was detected under allelic model, dominant model, the contrast of TC vs CC, and the contrast of TC vs CC + TT in Asian population. (T vs C: OR = 1.911, 95%CI: 1.182–3.090, P = 0.008; TC vs CC: OR = 1.948, 95%CI: 1.152–3.295, P = 0.013; TC + TT vs CC: OR = 1.994, 95%CI: 1.190–3.342, P = 0.009; TC vs CC + TT: OR = 1.926, 95%CI: 1.140–3.255, P = 0.014). However, the data suggest the rs2308327 and rs2308321 polymorphisms of the MGMT gene were nor associated with the susceptibility of prostate cancer. Based on the meta-analysis, MGMT rs12917 polymorphism increase the susceptibility to prostate cancer, which can be taken for a diagnosis and screening molecular biomarker for prostate cancer patients.

Keywords

MGMT PCa Prostate cancer Risk Meta-analysis 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

The study protocol has been approved by the local ethics committee.

References

  1. 1.
    Hung RJ, Baragatti M, Thomas D, McKay J, Szeszenia-Dabrowska N, Zaridze D, Lissowska J, Rudnai P, Fabianova E, Mates D, Foretova L, Janout V, Bencko V, Chabrier A, Moullan N, Canzian F, Hall J, Boffetta P, Brennan P (2007) Inherited predisposition of lung cancer: a hierarchical modeling approach to DNA repair and cell cycle control pathways. Cancer Epidem Biomar 16(12):2736–2744CrossRefGoogle Scholar
  2. 2.
    Chae MH, Jang JS, Kang HG, Park JH, Park JM, Lee WK, Kam S, Lee EB, Son JW, Park JY (2006)O6-alkylguanine-DNA alkyltransferase gene polymorphisms and the risk of primary lung cancer. Mol Carcinog 45(4):239–249CrossRefGoogle Scholar
  3. 3.
    Daniels DS, Woo TT, Luu KX, Noll DM, Clarke ND, Pegg AE, Tainer JA (2004) DNA binding and nucleotide flipping by the human DNA repair protein AGT. Nat Struct Mol Biol 11(8):714–720CrossRefGoogle Scholar
  4. 4.
    Calegari MA, Inno A, Monterisi S, Orlandi A, Santini D, Basso M, Cassano A, Martini M, Cenci T, de Pascalis I, Camarda F, Barbaro B, Larocca LM, Gori S, Tonini G, Barone C (2017) A phase 2 study of temozolomide in pretreated metastatic colorectal cancer with MGMT promoter methylation. Br J Cancer 116(10):1279–1286CrossRefGoogle Scholar
  5. 5.
    Chen GD, Qian DY, Li ZG, Fan GY, You KL, Wu YL (2017)Down-regulation of p16 and MGMT promotes the anti-proliferative and pro-apoptotic effects of 5-Aza-dC and radiation on cervical cancer cells. Cell Biochem Funct 35(8):488–496CrossRefGoogle Scholar
  6. 6.
    Tomaszowski KH, Hellmann N, Ponath V, Takatsu H, Shin HW, Kaina B (2017) Uptake of glucose-conjugated MGMT inhibitors in cancer cells: role of flippases and type IV P-type ATPases. Sci Rep 7(1):13925CrossRefGoogle Scholar
  7. 7.
    Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66(1):7–30CrossRefGoogle Scholar
  8. 8.
    Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA Cancer J Clin 67(1):7–30CrossRefGoogle Scholar
  9. 9.
    Liu TZ, Guo ZQ, Wang T, Cao Y, Huang D, Wang XH (2017)Meta-analysis of the role of IL-6 rs1800795 polymorphism in the susceptibility to prostate cancer: evidence based on 17 studies. Medicine 96(11):e6126CrossRefGoogle Scholar
  10. 10.
    Zhang L, Zhang Y, Zhang X, Hong B (2015)Prostaglandin-endoperoxide synthase 2 (PTGS2) rs20417 polymorphism and prostate cancer risk: a meta analysis. Int J Clin Exp Med 8(11):20454–20462Google Scholar
  11. 11.
    Agalliu I, Kwon EM, Salinas CA, Koopmeiners JS, Ostrander EA, Stanford JL (2010) Genetic variation in DNA repair genes and prostate cancer risk: results from a population-based study. Cancer Causes & Control 21(2):289–300CrossRefGoogle Scholar
  12. 12.
    Loh YH, Mitrou PN, Bowman R, Wood A, Jeffery H, Luben RN, Lentjes MA, Khaw KT, Rodwell SA (2010) MGMT Ile143Val polymorphism, dietary factors and the risk of breast, colorectal and prostate cancer in the European prospective investigation into cancer and nutrition (EPIC)-Norfolk study. DNA Repair 9(4):421–428CrossRefGoogle Scholar
  13. 13.
    Loh YH, Mitrou PN, Wood A, Luben RN, McTaggart A, Khaw KT, Rodwell SA (2011) SMAD7 and MGMT genotype variants and cancer incidence in the European prospective investigation into Cancer and nutrition (EPIC)-Norfolk study. Cancer Epidemiol 35(4):369–374CrossRefGoogle Scholar
  14. 14.
    Matullo G, Dunning AM, Guarrera S, Baynes C, Polidoro S, Garte S, Autrup H, Malaveille C, Peluso M, Airoldi L, Veglia F, Gormally E, Hoek G, Krzyzanowski M, Overvad K, Raaschou-Nielsen O, Clavel-Chapelon F, Linseisen J, Boeing H, Trichopoulou A, Palli D, Krogh V, Tumino R, Panico S, Bueno-De-Mesquita HB, Peeters PH, Lund E, Pera G, Martinez C, Dorronsoro M, Barricarte A, Tormo MJ, Quiros JR, Day NE, Key TJ, Saracci R, Kaaks R, Riboli E, Vineis P (2006) DNA repair polymorphisms and cancer risk in non-smokers in a cohort study. Carcinogenesis 27(5):997–1007CrossRefGoogle Scholar
  15. 15.
    Ritchey JD, Huang WY, Chokkalingam AP, Gao YT, Deng J, Levine P, Stanczyk FZ, Hsing AW (2005) Genetic variants of DNA repair genes and prostate cancer: a population-based study. Cancer Epidem Biomar 14(7):1703–1709CrossRefGoogle Scholar
  16. 16.
    Chuang LY, Chang HW, Lin MC, Yang CH (2012) Chaotic particle swarm optimization for detecting SNP-SNP interactions for CXCL12-related genes in breast cancer prevention. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 21(4):336–342CrossRefGoogle Scholar
  17. 17.
    Goodman JE, Mechanic LE, Luke BT, Ambs S, Chanock S, Harris CC (2006) Exploring SNP-SNP interactions and colon cancer risk using polymorphism interaction analysis. Int J Cancer 118(7):1790–1797CrossRefGoogle Scholar
  18. 18.
    Schwender H, Selinski S, Blaszkewicz M, Marchan R, Ickstadt K, Golka K, Hengstler JG (2012) Distinct SNP combinations confer susceptibility to urinary bladder cancer in smokers and non-smokers. PLoS One 7(12):e51880CrossRefGoogle Scholar
  19. 19.
    Hu Z, Wang H, Shao M, Jin G, Sun W, Wang Y, Liu H, Wang Y, Ma H, Qian J, Jin L, Wei Q, Lu D, Huang W, Shen H (2007) Genetic variants in MGMT and risk of lung cancer in southeastern Chinese: a haplotype-based analysis. Hum Mutat 28(5):431–440CrossRefGoogle Scholar
  20. 20.
    Huang J, Ye F, Chen H, Lu W, Xie X (2007) Amino acid substitution polymorphisms of the DNA repair gene MGMT and the susceptibility to cervical carcinoma. Carcinogenesis 28(6):1314–1322CrossRefGoogle Scholar
  21. 21.
    Krzesniak M, Butkiewicz D, Samojedny A, Chorazy M, Rusin M (2004) Polymorphisms in TDG and MGMT genes - epidemiological and functional study in lung cancer patients from Poland. Ann Hum Genet 68(Pt 4):300–312CrossRefGoogle Scholar
  22. 22.
    Li C, Liu J, Li A, Qian L, Wang X, Wei Q, Zhou J, Zhang Z (2005) Exon 3 polymorphisms and haplotypes of O6-methylguanine-DNA methyltransferase and risk of bladder cancer in southern China: a case-control analysis. Cancer Lett 227(1):49–57CrossRefGoogle Scholar
  23. 23.
    Liu Y, Scheurer ME, El-Zein R, Cao Y, Do KA, Gilbert M, Aldape KD, Wei Q, Etzel C, Bondy ML (2009) Association and interactions between DNA repair gene polymorphisms and adult glioma. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 18(1):204–214CrossRefGoogle Scholar
  24. 24.
    Shen J, Terry MB, Gammon MD, Gaudet MM, Teitelbaum SL, Eng SM, Sagiv SK, Neugut AI, Santella RM (2005) MGMT genotype modulates the associations between cigarette smoking, dietary antioxidants and breast cancer risk. Carcinogenesis 26(12):2131–2137CrossRefGoogle Scholar
  25. 25.
    Shen M, Purdue MP, Kricker A, Lan Q, Grulich AE, Vajdic CM, Turner J, Whitby D, Chanock S, Rothman N, Armstrong BK (2007) Polymorphisms in DNA repair genes and risk of non-Hodgkin's lymphoma in New South Wales, Australia. Haematologica 92(9):1180–1185CrossRefGoogle Scholar
  26. 26.
    Huang WY, Chow WH, Rothman N, Lissowska J, Llaca V, Yeager M, Zatonski W, Hayes RB (2005) Selected DNA repair polymorphisms and gastric cancer in Poland. Carcinogenesis 26(8):1354–1359CrossRefGoogle Scholar
  27. 27.
    Wang L, Liu H, Zhang Z, Spitz MR, Wei Q (2006) Association of genetic variants of O6-methylguanine-DNA methyltransferase with risk of lung cancer in non-Hispanic whites. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 15(12):2364–2369CrossRefGoogle Scholar
  28. 28.
    Liu J, Zhang R, Chen F, Yu C, Sun Y, Jia C, Zhang L, Salahuddin T, Li X, Lang J, Song X (2013) MGMT Leu84Phe polymorphism contributes to cancer susceptibility: evidence from 44 case-control studies. PLoS One 8(9):e75367CrossRefGoogle Scholar
  29. 29.
    Qiu ZX, Xue F, Shi XF, He X, Ma HN, Chen L, Chen PZ (2014) MGMT Leu84Phe gene polymorphism and lung cancer risk: a meta-analysis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 35(5):4381–4387CrossRefGoogle Scholar
  30. 30.
    Zhong Y, Huang Y, Huang Y, Zhang T, Ma C, Zhang S, Fan W, Chen H, Qian J, Lu D (2010) Effects of O6-methylguanine-DNA methyltransferase (MGMT) polymorphisms on cancer: a meta-analysis. Mutagenesis 25(1):83–95CrossRefGoogle Scholar
  31. 31.
    Hirschhorn JN, Lohmueller K, Byrne E, Hirschhorn K (2002) A comprehensive review of genetic association studies. Genetics in medicine : official journal of the American College of Medical Genetics 4(2):45–61CrossRefGoogle Scholar
  32. 32.
    Rodriguez C, Calle EE, Miracle-McMahill HL, Tatham LM, Wingo PA, Thun MJ, Heath CW Jr (1997) Family history and risk of fatal prostate cancer. Epidemiology (Cambridge, Mass) 8(6):653–657CrossRefGoogle Scholar

Copyright information

© Arányi Lajos Foundation 2019

Authors and Affiliations

  • Wei Zhang
    • 1
    • 2
  • Mingkai Liu
    • 1
  • Yue Li
    • 1
  • Shichao Song
    • 1
  • Kai Li
    • 1
  • Yongliang Ma
    • 3
    Email author
  1. 1.Department of UrologyAffiliated Hospital of Hebei UniversityBaodingChina
  2. 2.Hebei Key Laboratory of Chronic Kidney Diseases and Bone MetabolismBaodingChina
  3. 3.Department of UrologyFourth Hospital of Hebei Medical UniversityShijiazhuangChina

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