Abstract
Myeloperoxidase (MPO) is a phase I enzyme playing a crucial role in metabolically activating a wide range of procarcinogens, such as polycyclic aromatic hydrocarbons and aromatic amines. The G463A polymorphism in the promoter region of the MPO gene has been indicated in lung cancer risk. To investigate the precise association of MPO G463A polymorphism with the lung cancer risk, we performed this comprehensive meta-analysis with large available data published to date. The included 24 individual studies involving a total of 8,313 cases and 8,728 controls were identified by searching the PubMed, Embase, and Wanfang databases. The crude odds ratios (ORs) and the corresponding 95 % confidence intervals (CIs) were calculated to estimate the association. Stratified analyses by ethnicity, source of controls, smoking status, and histological types were also conducted. Overall, the MPO G463A polymorphism was negatively related to the development of lung cancer in the following genetic models (A vs. G, OR = 0.90, 95 % CI = 0.82–0.99, P OR = 0.029; GA vs. GG, OR = 0.89, 95 % CI = 0.80–0.98, P OR = 0.022; AA + GA vs. GG, OR = 0.89, 95 % CI = 0.81–0.98, P OR = 0.023). Stratified analyses by ethnicity indicated that the variant genotype of MPO G463A was associated with a decreased risk of lung cancer in Asians and Caucasians. Similar findings were observed among the smokers and population-based case–control studies. The MPO G463A polymorphism seemed to exert no effect on lung adenocarcinoma and squamous cell carcinoma. The comprehensive meta-analysis shows that the polymorphism of MPO G463A is a protective factor for lung cancer, particularly among the populations of Asians, Caucasians, and smokers.
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Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.
Steliga MA, Dresler CM. Epidemiology of lung cancer: smoking, secondhand smoke, and genetics. Surg Oncol Clin N Am. 2011;20:605–18.
Ginsberg MS. Epidemiology of lung cancer. Semin Roentgenol. 2005;40:83–9.
Ahn MJ, Park SY, Kim WK, Cho JH, Chang BJ, Kim DJ, et al. A single nucleotide polymorphism in the phospholipase D1 gene is associated with risk of non-small cell lung cancer. Int J Biomed Sci. 2012;8:121–8.
Kanzaki H, Ouchida M, Hanafusa H, Yamamoto H, Suzuki H, Yano M, et al. The association between RAD18 Arg302Gln polymorphism and the risk of human non-small-cell lung cancer. J Cancer Res Clin Oncol. 2008;134:211–7.
Zheng J, Jiang L, Zhang L, Yang L, Deng J, You Y, et al. Functional genetic variations in the IL-23 receptor gene are associated with risk of breast, lung and nasopharyngeal cancer in Chinese populations. Carcinogenesis. 2012;33:2409–16.
Klebanoff SJ. Myeloperoxidase. Proc Assoc Am Physicians. 1999;111:383–9.
Klebanoff SJ. Myeloperoxidase: friend and foe. J Leukoc Biol. 2005;77:598–625.
Anand U, Anand CV. Myeloperoxidase: a new twist to an old tale. Indian J Clin Biochem. 2012;27:107–9.
Wheatley-Price P, Asomaning K, Reid A, Zhai R, Su L, Zhou W, et al. Myeloperoxidase and superoxide dismutase polymorphisms are associated with an increased risk of developing pancreatic adenocarcinoma. Cancer. 2008;112:1037–42.
Ahn J, Gammon MD, Santella RM, Gaudet MM, Britton JA, Teitelbaum SL, et al. Myeloperoxidase genotype, fruit and vegetable consumption, and breast cancer risk. Cancer Res. 2004;64:7634–9.
Pabalan N, Jarjanazi H, Sung L, Li H, Ozcelik H. Menopausal status modifies breast cancer risk associated with the myeloperoxidase (MPO) G463A polymorphism in Caucasian women: a meta-analysis. PLoS One. 2012;7:e32389.
Li D, Diao Y, Li H, Fang X. Association of the polymorphisms of MTHFR C677T, VDR C352T, and MPO G463A with risk for esophageal squamous cell dysplasia and carcinoma. Arch Med Res. 2008;39:594–600.
Cochran WG. The comparison of percentages in matched samples. Biometrika. 1950;37:256–66.
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.
Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48.
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.
Stuck AE, Rubenstein LZ, Wieland D. Bias in meta-analysis detected by a simple, graphical test. Asymmetry detected in funnel plot was probably due to true heterogeneity. BMJ. 1998;316:469. author reply 70–1.
London SJ, Lehman TA, Taylor JA. Myeloperoxidase genetic polymorphism and lung cancer risk. Cancer Res. 1997;57:5001–3.
Cascorbi I, Henning S, Brockmoller J, Gephart J, Meisel C, Muller JM, et al. Substantially reduced risk of cancer of the aerodigestive tract in subjects with variant—463A of the myeloperoxidase gene. Cancer Res. 2000;60:644–9.
Le Marchand L, Seifried A, Lum A, Wilkens LR. Association of the myeloperoxidase -463G → a polymorphism with lung cancer risk. Cancer Epidemiol Biomarkers Prev. 2000;9:181–4.
Misra RR, Tangrea JA, Virtamo J, Ratnasinghe D, Andersen MR, Barrett M, et al. Variation in the promoter region of the myeloperoxidase gene is not directly related to lung cancer risk among male smokers in Finland. Cancer Lett. 2001;164:161–7.
Lv WF, Qi J, Xing DY, Tan W, Miao XP, Su W, et al. Lung cancer risk associated with gene polymorphism in myeloperoxidase (−463 G/A) in a Chinese population. Chin J Oncol. 2002;24:250–3 [Article in Chinese].
Feyler A, Voho A, Bouchardy C, Kuokkanen K, Dayer P, Hirvonen A, et al. Point: myeloperoxidase -463G → a polymorphism and lung cancer risk. Cancer Epidemiol Biomarkers Prev. 2002;11:1550–4.
Dally H, Gassner K, Jager B, Schmezer P, Spiegelhalder B, Edler L, et al. Myeloperoxidase (MPO) genotype and lung cancer histologic types: the MPO −463 A allele is associated with reduced risk for small cell lung cancer in smokers. Int J Cancer. 2002;102:530–5.
Lu W, Xing D, Qi J, Tan W, Miao X, Lin D. Genetic polymorphism in myeloperoxidase but not GSTM1 is associated with risk of lung squamous cell carcinoma in a Chinese population. Int J Cancer. 2002;102:275–9.
Schabath MB, Spitz MR, Delclos GL, Gunn GB, Whitehead LW, Wu X. Association between asbestos exposure, cigarette smoking, myeloperoxidase (MPO) genotypes, and lung cancer risk. Am J Ind Med. 2002;42:29–37.
Xu LL, Liu G, Miller DP, Zhou W, Lynch TJ, Wain JC, et al. Counterpoint: the myeloperoxidase -463G → a polymorphism does not decrease lung cancer susceptibility in Caucasians. Cancer Epidemiol Biomarkers Prev. 2002;11:1555–9.
Kantarci OH, Lesnick TG, Yang P, Meyer RL, Hebrink DD, McMurray CT, et al. Myeloperoxidase −463 (G → A) polymorphism associated with lower risk of lung cancer. Mayo Clin Proc. 2002;77:17–22.
Wu XM, Zhou YK, Ren S, Hao QL. Gene polymorphism of myeloperoxidase and genetic susceptibility to lung cancer. Chin J Cancer. 2003;22:912–5 [Article in Chinese].
Cajas-Salazar N, Sierra-Torres CH, Salama SA, Zwischenberger JB, Au WW. Combined effect of MPO, GSTM1 and GSTT1 polymorphisms on chromosome aberrations and lung cancer risk. Int J Hyg Environ Health. 2003;206:473–83.
Chevrier I, Stucker I, Houllier AM, Cenee S, Beaune P, Laurent-Puig P, et al. Myeloperoxidase: new polymorphisms and relation with lung cancer risk. Pharmacogenet. 2003;13:729–39.
Liu G, Zhou W, Wang LI, Park S, Miller DP, Xu LL, et al. MPO and SOD2 polymorphisms, gender, and the risk of non-small cell lung carcinoma. Cancer Lett. 2004;214:69–79.
Chan EC, Lam SY, Fu KH, Kwong YL. Polymorphisms of the GSTM1, GSTP1, MPO, XRCC1, and NQO1 genes in Chinese patients with non-small cell lung cancers: relationship with aberrant promoter methylation of the CDKN2A and RARB genes. Cancer Genet Cytogenet. 2005;162:10–20.
Larsen JE, Colosimo ML, Yang IA, Bowman R, Zimmerman PV, Fong KM. CYP1A1 Ile462Val and MPO G-463A interact to increase risk of adenocarcinoma but not squamous cell carcinoma of the lung. Carcinogenesis. 2006;27:525–32.
Park JH, Park JM, Kim EJ, Cha SI, Lee EB, Kim CH, et al. Myeloperoxidase -463G > A polymorphism and risk of primary lung cancer in a Korean population. Cancer Detect Prev. 2006;30:257–61.
Zhang TY, Hong XT, Wu YJ, Wu YM. Myeloperoxidase polymorphism in lung cancer patients of Henan Han population. J Zhengzhou Univ. 2007;42:448–50 [Article in Chinese].
Yang M, Choi Y, Hwangbo B, Lee JS. Combined effects of genetic polymorphisms in six selected genes on lung cancer susceptibility. Lung Cancer. 2007;57:135–42.
Zienolddiny S, Campa D, Lind H, Ryberg D, Skaug V, Stangeland LB, et al. A comprehensive analysis of phase I and phase II metabolism gene polymorphisms and risk of non-small cell lung cancer in smokers. Carcinogenesis. 2008;29:1164–9.
Yoon KA, Kim JH, Gil HJ, Hwang H, Hwangbo B, Lee JS. CYP1B1, CYP1A1, MPO, and GSTP1 polymorphisms and lung cancer risk in never-smoking Korean women. Lung Cancer. 2008;60:40–6.
Klinchid J, Chewaskulyoung B, Saeteng S, Lertprasertsuke N, Kasinrerk W, Cressey R. Effect of combined genetic polymorphisms on lung cancer risk in northern Thai women. Cancer Genet Cytogenet. 2009;195:143–9.
Arslan S, Pinarbasi H, Silig Y. Myeloperoxidase G-463A polymorphism and risk of lung and prostate cancer in a Turkish population. Mol Med Rep. 2011;4:87–92.
Wang S, Zhu J, Zhang R, Gu Z. Association between microsomal epoxide hydrolase 1 T113C polymorphism and susceptibility to lung cancer. Tumour Biol. 2013;34:1045–52.
Shiels MS, Chaturvedi AK, Katki HA, Gochuico BR, Caporaso NE, Engels EA. Circulating markers of interstitial lung disease and subsequent risk of lung cancer. Cancer Epidemiol Biomarkers Prev. 2011;20:2262–72.
Yang JP, Wang WB, Yang XX, Yang L, Ren L, Zhou FX, et al. The MPO-463G > A polymorphism and lung cancer risk: a meta-analysis based on 22 case–control studies. PLoS One. 2013;8:e65778.
Zhong L, Goldberg MS, Parent ME, Hanley JA. Exposure to environmental tobacco smoke and the risk of lung cancer: a meta-analysis. Lung Cancer. 2000;27:3–18.
Kiyohara C, Yoshimasu K, Takayama K, Nakanishi Y. NQO1, MPO, and the risk of lung cancer: a HuGE review. Genet Med. 2005;7:463–78.
Vineis P, Hoek G, Krzyzanowski M, Vigna-Taglianti F, Veglia F, Airoldi L, et al. Lung cancers attributable to environmental tobacco smoke and air pollution in non-smokers in different European countries: a prospective study. Environ Health. 2007;6:7.
Boffetta P, Nyberg F. Contribution of environmental factors to cancer risk. Br Med Bull. 2003;68:71–94.
Li QD, Li H, Wang MS, Diao TY, Zhou ZY, Fang QX, et al. Multi-susceptibility genes associated with the risk of the development stages of esophageal squamous cell cancer in Feicheng County. BMC Gastroenterol. 2011;11:74.
Koutros S, Andreotti G, Berndt SI, Hughes Barry K, Lubin JH, Hoppin JA, et al. Xenobiotic-metabolizing gene variants, pesticide use, and the risk of prostate cancer. Pharmacogenet Genomics. 2011;21:615–23.
Yuzhalin AE, Kutikhin AG. Common genetic variants in the myeloperoxidase and paraoxonase genes and the related cancer risk: a review. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2012;30:287–322.
Li Y, Ambrosone CB, McCullough MJ, Ahn J, Stevens VL, Thun MJ, et al. Oxidative stress-related genotypes, fruit and vegetable consumption and breast cancer risk. Carcinogenesis. 2009;30:777–84.
Risch HA, Howe GR, Jain M, Burch JD, Holowaty EJ, Miller AB. Are female smokers at higher risk for lung cancer than male smokers? A case–control analysis by histologic type. Am J Epidemiol. 1993;138:281–93.
Kreuzer M, Boffetta P, Whitley E, Ahrens W, Gaborieau V, Heinrich J, et al. Gender differences in lung cancer risk by smoking: a multicentre case–control study in Germany and Italy. Br J Cancer. 2000;82:227–33.
Dahabreh IJ, Trikalinos TA, Paulus JK. Parity and risk of lung cancer in women: systematic review and meta-analysis of epidemiological studies. Lung Cancer. 2012;76:150–8.
Schabath MB, Spitz MR, Zhang X, Delclos GL, Wu X. Genetic variants of myeloperoxidase and lung cancer risk. Carcinogenesis. 2000;21:1163–6.
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Li, J., Fu, Y., Zhao, B. et al. Myeloperoxidase G463A polymorphism and risk of lung cancer. Tumor Biol. 35, 821–829 (2014). https://doi.org/10.1007/s13277-013-1113-4
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DOI: https://doi.org/10.1007/s13277-013-1113-4