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GPX1 Pro198Leu polymorphism and breast cancer risk: a meta-analysis

  • Epidemiology
  • Published:
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Abstract

A genetic polymorphism at codon 198 in the human glutathione peroxidase 1 gene was reported to be associated with several cancers. However, this relationship remains controversial, especially in breast cancer. For better understanding the effect of GPX1 Pro198Leu polymorphism on breast cancer, a meta-analysis was performed. By searching relevant literatures, a total of six case–control studies, containing 5,509 breast cancer cases and 6,542 healthy controls, were included. The strength of association between GPX1 Pro198Leu polymorphism and breast cancer risk was assessed by odds ratio (OR) with the corresponding 95% confidence interval (95%CI). And the results strongly suggested that there was no significant association between variant Leu allele and breast cancer susceptibility in overall comparisons in all genetic models [additive model: OR, 1.04; 95% CI, 0.92–1.18; P = 0.555; dominant model: OR, 1.01; 95% CI, 0.94–1.09; P = 0.777; recessive model: OR, 1.04; 95% CI, 0.92–1.18; P = 0.536]. However in subgroup analysis, an elevated risk in African population with variant Leu allele was revealed in additive (OR, 1.91; 95% CI, 1.02–3.58; P = 0.044) and recessive (OR, 2.09; 95% CI, 1.16–3.76; P = 0.014) genetic model. No apparent association between this polymorphism and different menopausal status (premenopausal and postmenopausal) and the other ethnicities (almost Caucasians) was showed. In conclusion, this meta-analysis strongly suggests that GPX1 Pro198Leu polymorphism is not associated with breast cancer risk in Caucasians, and an elevated risk in Africans needs large-scale investigations to confirm.

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References

  1. Ambrosone CB (2000) Oxidants and antioxidants in breast cancer. Antioxid Redox Signal 2:903–917. doi:10.1089/ars.2000.2.4-903

    Article  CAS  PubMed  Google Scholar 

  2. Brigelius-Flohé R (1999) Tissue-specific functions of individual glutathione peroxidases. Free Radic Biol Med 27:951–965. doi:10.1016/S0891-5849(99)00173-2

    Article  PubMed  Google Scholar 

  3. Matés JM, Pérez-Gómez C, Núñez de Castro I (1999) Antioxidant enzymes and human diseases. Clin Biochem 32:595–603. doi:10.1016/S0009-9120(99)00075-2

    Article  PubMed  Google Scholar 

  4. Ravn-Haren G, Olsen A, Tjønneland A, Dragsted LO, Nexø BA, Wallin H, Overvad K, Raaschou-Nielsen O, Vogel U (2006) Associations between GPX1 Pro198Leu polymorphism, erythrocyte GPX activity, alcohol consumption and breast cancer risk in a prospective cohort study. Carcinogenesis 27:820–825. doi:10.1093/carcin/bgi267

    Article  CAS  PubMed  Google Scholar 

  5. Arsova-Sarafinovska Z, Matevska N, Eken A, Petrovski D, Banev S, Dzikova S, Georgiev V, Sikole A, Erdem O, Sayal A, Aydin A, Dimovski AJ (2009) Glutathione peroxidase 1 (GPX1) genetic polymorphism, erythrocyte GPX activity, and prostate cancer risk. Int Urol Nephrol 41:63–70. doi:10.1007/s11255-008-9407-y

    Article  CAS  PubMed  Google Scholar 

  6. Hansen RD, Krath BN, Frederiksen K, Tjønneland A, Overvad K, Roswall N, Loft S, Dragsted LO, Vogel U, Raaschou-Nielsen O (2009) GPX1 Pro(198)Leu polymorphism, erythrocyte GPX activity, interaction with alcohol consumption and smoking, and risk of colorectal cancer. Mutat Res 664:13–19. doi:10.1016/j.mrfmmm.2009.01.009

    CAS  PubMed  Google Scholar 

  7. Hansen R, Saebø M, Skjelbred CF, Nexø BA, Hagen PC, Bock G, Bowitz Lothe IM, Johnson E, Aase S, Hansteen IL, Vogel U, Kure EH (2005) GPX Pro198Leu and OGG1 Ser326Cys polymorphisms and risk of development of colorectal adenomas and colorectal cancer. Cancer Lett 229:85–91. doi:10.1016/j.canlet.2005.04.019

    Article  CAS  PubMed  Google Scholar 

  8. Raaschou-Nielsen O, Sørensen M, Hansen RD, Frederiksen K, Tjønneland A, Overvad K, Vogel U (2007) GPX1 Pro198Leu polymorphism, interactions with smoking and alcohol consumption, and risk for lung cancer. Cancer Lett 247:293–300. doi:10.1016/j.canlet.2006.05.006

    Article  CAS  PubMed  Google Scholar 

  9. Ezzikouri S, El Feydi AE, Afifi R, Benazzouz M, Hassar M, Pineau P, Benjelloun S (2010) Polymorphisms in antioxidant defence genes and susceptibility to hepatocellular carcinoma in a Moroccan population. Free Radic Res 44:208–216. doi:10.3109/10715760903402906

    Article  CAS  PubMed  Google Scholar 

  10. Hu YJ, Diamond AM (2003) Role of glutathione peroxidase 1 in breast cancer: loss of heterozygosity and allelic differences in the response to selenium. Cancer Res 63:3347–3351

    CAS  PubMed  Google Scholar 

  11. Cox DG, Hankinson SE, Kraft P, Hunter DJ (2004) No association between GPX1 Pro198Leu and breast cancer risk. Cancer Epidemiol Biomarkers Prev 13:1821–1822

    CAS  PubMed  Google Scholar 

  12. Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748

    CAS  PubMed  Google Scholar 

  13. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    Article  CAS  PubMed  Google Scholar 

  14. Cochran WG (1954) The combination of estimates from different experiments. Biometrics 10:101–129

    Article  Google Scholar 

  15. Tobias A (1999) Assessing the influence of a single study in the meta-analysis estimate. Stata Tech Bull 8:15–17

    Google Scholar 

  16. Egger M, Davey SG, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    CAS  PubMed  Google Scholar 

  17. Cox DG, Tamimi RM, Hunter DJ (2006) Gene × Gene interaction between MnSOD and GPX-1 and breast cancer risk: a nested case-control study. BMC Cancer 6:217. doi:10.1186/1471-2407-6-217

    Article  PubMed  Google Scholar 

  18. Knight JA, Onay UV, Wells S, Li H, Shi EJ, Andrulis IL, Ozcelik H (2004) Genetic variants of GPX1 and SOD2 and breast cancer risk at the Ontario site of the Breast Cancer Family Registry. Cancer Epidemiol Biomarkers Prev 13:146–149. doi:10.1158/1055-9965.EPI-03-0164

    Article  CAS  PubMed  Google Scholar 

  19. Ahn J, Gammon MD, Santella RM, Gaudet MM, Britton JA, Teitelbaum SL, Terry MB, Neugut AI, Ambrosone CB (2005) No association between glutathione peroxidase Pro198Leu polymorphism and breast cancer risk. Cancer Epidemiol Biomarkers Prev 14:2459–2461. doi:10.1158/1055-9965.EPI-05-0459

    Article  CAS  PubMed  Google Scholar 

  20. Cebrian A, Pharoah PD, Ahmed S, Smith PL, Luccarini C, Luben R, Redman K, Munday H, Easton DF, Dunning AM, Ponder BA (2006) Tagging single-nucleotide polymorphisms in antioxidant defense enzymes and susceptibility to breast cancer. Cancer Res 66:1225–1233. doi:10.1158/0008-5472.CAN-05-1857

    Article  CAS  PubMed  Google Scholar 

  21. Hu YJ, Dolan ME, Bae R, Yee H, Roy M, Glickman R, Kiremidjian-Schumacher L, Diamond AM (2004) Allelic loss at the GPx-1 locus in cancer of the head and neck. Biol Trace Elem Res 101:97–106. doi:10.1385/BTER:101:2:097

    Article  CAS  PubMed  Google Scholar 

  22. Ratnasinghe D, Tangrea JA, Andersen MR, Barrett MJ, Virtamo J, Taylor PR, Albanes D (2000) Glutathione peroxidase codon 198 polymorphism variant increases lung cancer risk. Cancer Res 60:6381–6383

    CAS  PubMed  Google Scholar 

  23. Skuladottir H, Autrup H, Autrup J, Tjoenneland A, Overvad K, Ryberg D, Haugen A, Olsen JH (2005) Polymorphisms in genes involved in xenobiotic metabolism and lung cancer risk under the age of 60 years. A pooled study of lung cancer patients in Denmark and Norway. Lung Cancer 48:187–199. doi:10.1016/j.lungcan.2004.10.013

    Article  PubMed  Google Scholar 

  24. Rosenberger A, Illig T, Korb K, Klopp N, Zietemann V, Wölke G, Meese E, Sybrecht G, Kronenberg F, Cebulla M, Degen M, Drings P, Gröschel A, Konietzko N, Kreymborg KG, Häussinger K, Höffken G, Jilge B, Ko YD, Morr H, Schmidt C, Schmidt EW, Täuscher D, Bickeböller H, Wichmann HE (2008) Do genetic factors protect for early onset lung cancer? A case control study before the age of 50 years. BMC Cancer 8:60. doi:10.1186/1471-2407-8-60

    Article  PubMed  Google Scholar 

  25. Suzana S, Cham BG, Ahmad Rohi G, Mohd Rizal R, Fairulnizal MN, Normah H, Fatimah A (2009) Relationship between selenium and breast cancer: a case-control study in the Klang Valley. Singapore Med J 50:265–269

    CAS  PubMed  Google Scholar 

  26. Schrauzer GN (2009) Selenium and selenium-antagonistic elements in nutritional cancer prevention. Crit Rev Biotechnol 29:10–17. doi:10.1080/07388550802658048

    Article  CAS  PubMed  Google Scholar 

  27. Park Y, Brinton LA, Subar AF, Hollenbeck A, Schatzkin A (2009) Dietary fiber intake and risk of breast cancer in postmenopausal women: the National Institutes of Health-AARP Diet and Health Study. Am J Clin Nutr 90:664–671. doi:10.3945/ajcn.2009.27758

    Article  CAS  PubMed  Google Scholar 

  28. Aune D, De Stefani E, Ronco A, Boffetta P, Deneo-Pellegrini H, Acosta G, Mendilaharsu M (2009) Fruits, vegetables and the risk of cancer: a multisite case-control study in Uruguay. Asian Pac J Cancer Prev 10:419–428

    PubMed  Google Scholar 

  29. Nagel G, Linseisen J, van Gils CH, Peeters PH, Boutron-Ruault MC, Clavel-Chapelon F, Romieu I, Tjønneland A, Olsen A, Roswall N, Witt PM, Overvad K, Rohrmann S, Kaaks R, Drogan D, Boeing H, Trichopoulou A, Stratigakou V, Zylis D, Engeset D, Lund E, Skeie G, Berrino F, Grioni S, Mattiello A, Masala G, Tumino R, Zanetti R, Ros MM, Bueno-de-Mesquita HB, Ardanaz E, Sánchez MJ, Huerta JM, Amiano P, Rodríguez L, Manjer J, Wirfält E, Lenner P, Hallmans G, Spencer EA, Key TJ, Bingham S, Khaw KT, Rinaldi S, Slimani N, Boffetta P, Gallo V, Norat T, Riboli E (2010) Dietary beta-carotene, vitamin C and E intake and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Breast Cancer Res Treat 119:753–765. doi:10.1007/s10549-009-0444-8

    Article  CAS  PubMed  Google Scholar 

  30. Boyle P, Boffetta P (2009) Alcohol consumption and breast cancer risk. Breast Cancer Res. doi:10.1186/bcr2422

  31. Ichimura Y, Habuchi T, Tsuchiya N, Wang L, Oyama C, Sato K, Nishiyama H, Ogawa O, Kato T (2004) Increased risk of bladder cancer associated with a glutathione peroxidase 1 codon 198 variant. J Urol 172:728–732. doi:10.1097/01.ju.0000130942.40597.9d

    Article  CAS  PubMed  Google Scholar 

  32. Qiao YL, Taylor PR, Yao SX, Schatzkin A, Mao BL, Lubin J, Rao JY, McAdams M, Xuan XZ, Li JY (1989) Relation of radon exposure and tobacco use to lung cancer among tin miners in Yunnan Province, China. Am J Ind Med 16:511–521

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Oncology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, People’s Republic of China

    Jia Hu, Ning Wang & Ya-Jie Wang

  2. Department of Respiration, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, People’s Republic of China

    Guo-Wu Zhou

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  1. Jia Hu
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  4. Ya-Jie Wang
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Correspondence to Ya-Jie Wang.

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Jia Hu and Guo-Wu Zhou equally contributed to this study.

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Hu, J., Zhou, GW., Wang, N. et al. GPX1 Pro198Leu polymorphism and breast cancer risk: a meta-analysis. Breast Cancer Res Treat 124, 425–431 (2010). https://doi.org/10.1007/s10549-010-0841-z

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  • DOI: https://doi.org/10.1007/s10549-010-0841-z

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