Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Tumor Biology
Published in: Tumor Biology 1/2014

01-01-2014 | Research Article

Myeloperoxidase G463A polymorphism and risk of lung cancer

Authors: Junrui Li, Yingju Fu, Baochun Zhao, Ying Xiao, Ruiying Chen

Published in: Tumor Biology | Issue 1/2014

Login to get access

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.
Literature
1.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.PubMedCrossRef
2.
Steliga MA, Dresler CM. Epidemiology of lung cancer: smoking, secondhand smoke, and genetics. Surg Oncol Clin N Am. 2011;20:605–18.PubMedCrossRef
3.
4.
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.PubMed
5.
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.PubMedCrossRef
6.
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.PubMedCrossRef
7.
Klebanoff SJ. Myeloperoxidase. Proc Assoc Am Physicians. 1999;111:383–9.PubMed
8.
9.
10.
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.PubMedCrossRef
11.
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.PubMedCrossRef
12.
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.PubMedCentralPubMedCrossRef
13.
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.PubMedCrossRef
14.
Cochran WG. The comparison of percentages in matched samples. Biometrika. 1950;37:256–66.PubMed
15.
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.PubMedCrossRef
16.
Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48.PubMed
17.
18.
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.PubMedCrossRef
19.
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.PubMedCrossRef
20.
London SJ, Lehman TA, Taylor JA. Myeloperoxidase genetic polymorphism and lung cancer risk. Cancer Res. 1997;57:5001–3.PubMed
21.
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.PubMed
22.
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.PubMed
23.
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.PubMedCrossRef
24.
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].
25.
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.PubMed
26.
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.PubMedCrossRef
27.
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.PubMedCrossRef
28.
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.PubMedCrossRef
29.
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.PubMed
30.
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.PubMedCrossRef
31.
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].
32.
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.PubMedCrossRef
33.
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.CrossRef
34.
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.PubMedCrossRef
35.
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.PubMedCrossRef
36.
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.PubMedCrossRef
37.
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.PubMedCrossRef
38.
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].
39.
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.PubMedCrossRef
40.
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.PubMedCrossRef
41.
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.PubMedCrossRef
42.
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.PubMedCrossRef
43.
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.PubMed
44.
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.PubMedCrossRef
45.
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.PubMedCentralPubMedCrossRef
46.
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.PubMedCentralPubMedCrossRef
47.
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.PubMedCrossRef
48.
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.PubMedCrossRef
49.
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.PubMedCentralPubMedCrossRef
50.
Boffetta P, Nyberg F. Contribution of environmental factors to cancer risk. Br Med Bull. 2003;68:71–94.PubMedCrossRef
51.
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.PubMedCentralPubMedCrossRef
52.
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.PubMedCentralPubMedCrossRef
53.
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.PubMedCrossRef
54.
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.PubMedCrossRef
55.
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.PubMed
56.
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.PubMedCentralPubMedCrossRef
57.
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.PubMedCrossRef
58.
Schabath MB, Spitz MR, Zhang X, Delclos GL, Wu X. Genetic variants of myeloperoxidase and lung cancer risk. Carcinogenesis. 2000;21:1163–6.PubMedCrossRef
Metadata
Title
Myeloperoxidase G463A polymorphism and risk of lung cancer
Authors
Junrui Li
Yingju Fu
Baochun Zhao
Ying Xiao
Ruiying Chen
Publication date
01-01-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 1/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1113-4

Other articles of this Issue 1/2014

Tumor Biology 1/2014 Go to the issue

Research Article

A functional polymorphism in the miR-146a gene is associated with the risk of childhood acute lymphoblastic leukemia: a preliminary report

Research Article

Association between vestibular schwannomas and mobile phone use

Research Article

SMAD7 rs12953717 polymorphism contributes to increased risk of colorectal cancer

Research Article

Association of rs2233678 and rs2233679 polymorphisms in the PIN1 gene with cancer risk: a meta-analysis

Research Article

Association between glutathione S-transferases M1 and T1 gene polymorphisms and prostate cancer risk: a systematic review and meta-analysis

Research Article

CARMA3 is overexpressed in human glioma and promotes cell invasion through MMP9 regulation in A172 cell line
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits