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Published in: Pathology & Oncology Research 2/2020

01-04-2020 | Prostate Cancer | Original Article

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

Authors: Wei Zhang, Mingkai Liu, Yue Li, Shichao Song, Kai Li, Yongliang Ma

Published in: Pathology & Oncology Research | Issue 2/2020

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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.
Literature
1.
go back to reference 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):2736–2744CrossRef 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):2736–2744CrossRef
2.
go back to reference 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):239–249CrossRef 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):239–249CrossRef
3.
go back to reference 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):714–720CrossRef 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):714–720CrossRef
4.
go back to reference 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):1279–1286CrossRef 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):1279–1286CrossRef
5.
go back to reference 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):488–496CrossRef 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):488–496CrossRef
6.
go back to reference 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):13925CrossRef 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):13925CrossRef
7.
go back to reference Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66(1):7–30CrossRef Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66(1):7–30CrossRef
8.
go back to reference Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA Cancer J Clin 67(1):7–30CrossRef Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA Cancer J Clin 67(1):7–30CrossRef
9.
go back to reference 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):e6126CrossRef 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):e6126CrossRef
10.
go back to reference 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):20454–20462PubMedPubMedCentral 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):20454–20462PubMedPubMedCentral
11.
go back to reference 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):289–300CrossRef 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):289–300CrossRef
12.
go back to reference 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):421–428CrossRef 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):421–428CrossRef
13.
go back to reference 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):369–374CrossRef 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):369–374CrossRef
14.
go back to reference 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):997–1007CrossRef 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):997–1007CrossRef
15.
go back to reference 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):1703–1709CrossRef 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):1703–1709CrossRef
16.
go back to reference 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):336–342CrossRef 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):336–342CrossRef
17.
go back to reference 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):1790–1797CrossRef 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):1790–1797CrossRef
18.
go back to reference 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):e51880CrossRef 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):e51880CrossRef
19.
go back to reference 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):431–440CrossRef 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):431–440CrossRef
20.
go back to reference 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):1314–1322CrossRef 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):1314–1322CrossRef
21.
go back to reference 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):300–312CrossRef 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):300–312CrossRef
22.
go back to reference 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):49–57CrossRef 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):49–57CrossRef
23.
go back to reference 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):204–214CrossRef 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):204–214CrossRef
24.
go back to reference 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):2131–2137CrossRef 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):2131–2137CrossRef
25.
go back to reference 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):1180–1185CrossRef 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):1180–1185CrossRef
26.
go back to reference 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):1354–1359CrossRef 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):1354–1359CrossRef
27.
go back to reference 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):2364–2369CrossRef 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):2364–2369CrossRef
28.
go back to reference 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):e75367CrossRef 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):e75367CrossRef
29.
go back to reference 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):4381–4387CrossRef 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):4381–4387CrossRef
30.
go back to reference 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):83–95CrossRef 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):83–95CrossRef
31.
go back to reference 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):45–61CrossRef 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):45–61CrossRef
32.
go back to reference 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):653–657CrossRef 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):653–657CrossRef
Metadata
Title
The Role of O6-methylguanine-DNA Methyltransferase Polymorphisms in Prostate Cancer Susceptibility: a Meta-Analysis
Authors
Wei Zhang
Mingkai Liu
Yue Li
Shichao Song
Kai Li
Yongliang Ma
Publication date
01-04-2020
Publisher
Springer Netherlands
Published in
Pathology & Oncology Research / Issue 2/2020
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-019-00672-7

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