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Four polymorphisms in cytochrome P450 1A1 (CYP1A1) gene and breast cancer risk: a meta-analysis

  • Epidemiology
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An Erratum to this article was published on 30 July 2010

Abstract

Cytochrome P450s are enzymes which catalyze Phase-I metabolism reactions; cytochrome P450 1A1 (CYP1A1) is a member of the CYP1 family and participates in the metabolism of a vast number of xenobiotics, as well as endogenous substrates. Four single nucleotide polymorphisms in CYP1A1 have been studied concerning their potential implication in terms of breast cancer risk: T3801C, T3205C, A2455G (Ile462Val), and C2453A (Thr461Asp); controversy exists regarding their role. This meta-analysis aims to examine whether the four aforementioned polymorphisms are associated with breast cancer risk. Separate analyses were performed on Caucasian, Chinese, and African populations, as well as on premenopausal and postmenopausal women. Eligible articles were identified by a search of MEDLINE bibliographical database for the period up to October 2009. Concerning T3801C, 32 studies were eligible (11,909 cases and 16,179 controls), 29 studies (12,257 cases and 20,379 controls) were eligible for A2455G, 11 studies (7,189 cases and 8,491 controls) were eligible for C2453A, and eight studies were eligible for T3205C (1,378 cases and 1,642 controls). Pooled odds ratios (OR) were appropriately derived from fixed- or random-effect models. Sensitivity analysis excluding studies whose genotype frequencies in controls significantly deviated from Hardy–Weinberg equilibrium was performed. Homozygous subjects of Caucasian origin carrying the A2455G G allele exhibited elevated breast cancer risk (pooled OR = 2.185, 95% CI 1.253–3.808, fixed effects), whereas heterozygous carriers did not (pooled OR = 1.062, 95% CI 0.852–1.323, random effects). A2455G polymorphism status was not associated with breast cancer risk in Chinese subjects or specifically in premenopausal/postmenopausal women. T3801C, T3205C, and C2453A status were not associated with breast cancer risk at any analysis. In conclusion, this meta-analysis points to the A2455G G allele as a risk factor for breast cancer among Caucasian subjects. On the contrary, T3801C, T3205C, and C2453A status does not seem capable of modifying breast cancer risk.

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References

  1. Androutsopoulos VP, Tsatsakis AM, Spandidos DA (2009) Cytochrome P450 CYP1A1: wider roles in cancer progression and prevention. BMC Cancer 9:187

    Article  PubMed  PubMed Central  Google Scholar 

  2. McManus ME, Burgess WM, Veronese ME, Huggett A, Quattrochi LC, Tukey RH (1990) Metabolism of 2-acetylaminofluorene and benzo(a)pyrene and activation of food-derived heterocyclic amine mutagens by human cytochromes P-450. Cancer Res 50:3367–3376

    CAS  PubMed  Google Scholar 

  3. Spink DC, Eugster HP, Lincoln DW II, Schuetz JD, Schuetz EG, Johnson JA, Kaminsky LS, Gierthy JF (1992) 17 beta-estradiol hydroxylation catalyzed by human cytochrome P450 1A1: a comparison of the activities induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in MCF-7 cells with those from heterologous expression of the cDNA. Arch Biochem Biophys 293:342–348

    Article  CAS  PubMed  Google Scholar 

  4. Masson LF, Sharp L, Cotton SC, Little J (2005) Cytochrome P-450 1A1 gene polymorphisms and risk of breast cancer: a HuGE review. Am J Epidemiol 161:901–915

    Article  CAS  PubMed  Google Scholar 

  5. Crofts F, Taioli E, Trachman J, Cosma GN, Currie D, Toniolo P, Garte SJ (1994) Functional significance of different human CYP1A1 genotypes. Carcinogenesis 15:2961–2963

    Article  CAS  PubMed  Google Scholar 

  6. Garte S, Ganguly S, Taioli E (2003) Effect of genotype on steady-state CYP1A1 gene expression in human peripheral lymphocytes. Biochem Pharmacol 65:441–445

    Article  CAS  PubMed  Google Scholar 

  7. Shaik AP, Jamil K, Das P (2009) CYP1A1 polymorphisms and risk of prostate cancer: a meta-analysis. Urol J 6:78–86

    PubMed  Google Scholar 

  8. Zhuo WL, Zhang YS, Wang Y, Zhuo XL, Zhu B, Cai L, Chen ZT (2009) Association studies of CYP1A1 and GSTM1 polymorphisms with esophageal cancer risk: evidence-based meta-analyses. Arch Med Res 40:169–179

    Article  CAS  PubMed  Google Scholar 

  9. Varela-Lema L, Taioli E, Ruano-Ravina A, Barros-Dios JM, Anantharaman D, Benhamou S, Boccia S, Bhisey RA, Cadoni G, Capoluongo E et al (2008) Meta-analysis and pooled analysis of GSTM1 and CYP1A1 polymorphisms and oral and pharyngeal cancers: a HuGE-GSEC review. Genet Med 10:369–384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Shi X, Zhou S, Wang Z, Zhou Z (2008) CYP1A1 and GSTM1 polymorphisms and lung cancer risk in Chinese populations: a meta-analysis. Lung Cancer 59:155–163

    Article  PubMed  Google Scholar 

  11. Chen C, Huang Y, Li Y, Mao Y, Xie Y (2007) Cytochrome P450 1A1 (CYP1A1) T3801C and A2455G polymorphisms in breast cancer risk: a meta-analysis. J Hum Genet 52:423–435

    Article  CAS  PubMed  Google Scholar 

  12. Economopoulos KP, Sergentanis TN (2009) XRCC3 Thr241Met polymorphism and breast cancer risk: a meta-analysis. Breast Cancer Res Treat. doi:10.1007/s10549-009-0562-3

  13. Economopoulos KP, Sergentanis TN (2009) Differential effects of MDM2 SNP309 polymorphism on breast cancer risk along with race: a meta-analysis. Breast Cancer Res Treat. doi:10.1007/s10549-009-0467-1

  14. Sergentanis TN, Economopoulos KP (2009) GSTT1 and GSTP1 polymorphisms and breast cancer risk: a meta-analysis. Breast Cancer Res Treat. doi:10.1007/s10549-009-0520-0

  15. Sergentanis TN, Economopoulos KP (2009) Association of two CASP8 polymorphisms with breast cancer risk: a meta-analysis. Breast Cancer Res Treat. doi:10.1007/s10549-009-0471-5

  16. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Thakkinstian A, McElduff P, D’Este C, Duffy D, Attia J (2005) A method for meta-analysis of molecular association studies. Stat Med 24:1291–1306

    Article  PubMed  Google Scholar 

  19. Rohlfs RV, Weir BS (2008) Distributions of Hardy–Weinberg equilibrium test statistics. Genetics 180:1609–1616

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Nakachi K, Imai K, Hayashi S, Kawajiri K (1993) Polymorphisms of the CYP1A1 and glutathione S-transferase genes associated with susceptibility to lung cancer in relation to cigarette dose in a Japanese population. Cancer Res 53:2994–2999

    CAS  PubMed  Google Scholar 

  21. Taioli E, Trachman J, Chen X, Toniolo P, Garte SJ (1995) A CYP1A1 restriction fragment length polymorphism is associated with breast cancer in African-American women. Cancer Res 55:3757–3758

    CAS  PubMed  Google Scholar 

  22. Moysich KB, Shields PG, Freudenheim JL, Schisterman EF, Vena JE, Kostyniak P, Greizerstein H, Marshall JR, Graham S, Ambrosone CB (1999) Polychlorinated biphenyls, cytochrome P4501A1 polymorphism, and postmenopausal breast cancer risk. Cancer Epidemiol Biomarkers Prev 8:41–44

    CAS  PubMed  Google Scholar 

  23. Huang CS, Chern HD, Chang KJ, Cheng CW, Hsu SM, Shen CY (1999) Breast cancer risk associated with genotype polymorphism of the estrogen-metabolizing genes CYP17, CYP1A1, and COMT: a multigenic study on cancer susceptibility. Cancer Res 59:4870–4875

    CAS  PubMed  Google Scholar 

  24. Laden F, Ishibe N, Hankinson SE, Wolff MS, Gertig DM, Hunter DJ, Kelsey KT (2002) Polychlorinated biphenyls, cytochrome P450 1A1, and breast cancer risk in the Nurses’ Health Study. Cancer Epidemiol Biomarkers Prev 11:1560–1565

    CAS  PubMed  Google Scholar 

  25. Miyoshi Y, Ando A, Hasegawa S, Ishitobi M, Yamamura J, Irahara N, Tanji Y, Taguchi T, Tamaki Y, Noguchi S (2003) Association of genetic polymorphisms in CYP19 and CYP1A1 with the oestrogen receptor-positive breast cancer risk. Eur J Cancer 39:2531–2537

    Article  CAS  PubMed  Google Scholar 

  26. Li Y, Millikan RC, Bell DA, Cui L, Tse CK, Newman B, Conway K (2005) Polychlorinated biphenyls, cytochrome P450 1A1 (CYP1A1) polymorphisms, and breast cancer risk among African American women and white women in North Carolina: a population-based case-control study. Breast Cancer Res 7:R12–R18

    Article  CAS  PubMed  Google Scholar 

  27. Justenhoven C, Hamann U, Schubert F, Zapatka M, Pierl CB, Rabstein S, Selinski S, Mueller T, Ickstadt K, Gilbert M et al (2008) Breast cancer: a candidate gene approach across the estrogen metabolic pathway. Breast Cancer Res Treat 108:137–149

    Article  CAS  PubMed  Google Scholar 

  28. Hayashi S, Watanabe J, Kawajiri K (1992) High susceptibility to lung cancer analyzed in terms of combined genotypes of P450IA1 and Mu-class glutathione S-transferase genes. Jpn J Cancer Res 83:866–870

    Article  CAS  PubMed  Google Scholar 

  29. Taioli E, Bradlow HL, Garbers SV, Sepkovic DW, Osborne MP, Trachman J, Ganguly S, Garte SJ (1999) Role of estradiol metabolism and CYP1A1 polymorphisms in breast cancer risk. Cancer Detect Prev 23:232–237

    Article  CAS  PubMed  Google Scholar 

  30. Ambrosone CB, Freudenheim JL, Graham S, Marshall JR, Vena JE, Brasure JR, Laughlin R, Nemoto T, Michalek AM, Harrington A et al (1995) Cytochrome P4501A1 and glutathione S-transferase (M1) genetic polymorphisms and postmenopausal breast cancer risk. Cancer Res 55:3483–3485

    CAS  PubMed  Google Scholar 

  31. Huang CS, Shen CY, Chang KJ, Hsu SM, Chern HD (1999) Cytochrome P4501A1 polymorphism as a susceptibility factor for breast cancer in postmenopausal Chinese women in Taiwan. Br J Cancer 80:1838–1843

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ishibe N, Hankinson SE, Colditz GA, Spiegelman D, Willett WC, Speizer FE, Kelsey KT, Hunter DJ (1998) Cigarette smoking, cytochrome P450 1A1 polymorphisms, and breast cancer risk in the Nurses’ Health Study. Cancer Res 58:667–671

    CAS  PubMed  Google Scholar 

  33. Miyoshi Y, Takahashi Y, Egawa C, Noguchi S (2002) Breast cancer risk associated with CYP1A1 genetic polymorphisms in Japanese women. Breast J 8:209–215

    Article  CAS  PubMed  Google Scholar 

  34. Li Y, Millikan RC, Bell DA, Cui L, Tse CK, Newman B, Conway K (2004) Cigarette smoking, cytochrome P4501A1 polymorphisms, and breast cancer among African-American and white women. Breast Cancer Res 6:R460–R473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. The Marie-Genica Consortium (2009) Genetic polymorphisms in phase I and phase II enzymes and breast cancer risk associated with menopausal hormone therapy in postmenopausal women. Breast Cancer Res Treat. doi:10.1007/s10549-009-0470-0

  36. Tempfer CB, Hefler LA, Schneeberger C, Huber JC (2006) How valid is single nucleotide polymorphism (SNP) diagnosis for the individual risk assessment of breast cancer? Gynecol Endocrinol 22:155–159

    Article  CAS  PubMed  Google Scholar 

  37. Rebbeck TR, Rosvold EA, Duggan DJ, Zhang J, Buetow KH (1994) Genetics of CYP1A1: coamplification of specific alleles by polymerase chain reaction and association with breast cancer. Cancer Epidemiol Biomarkers Prev 3:511–514

    CAS  PubMed  Google Scholar 

  38. Goth-Goldstein R, Stampfer MR, Erdmann CA, Russell M (2000) Interindividual variation in CYP1A1 expression in breast tissue and the role of genetic polymorphism. Carcinogenesis 21:2119–2122

    Article  CAS  PubMed  Google Scholar 

  39. Kang D (2003) Genetic polymorphisms and cancer susceptibility of breast cancer in Korean women. J Biochem Mol Biol 36:28–34

    Article  CAS  PubMed  Google Scholar 

  40. Zhu K, Hunter S, Payne-Wilks K, Sutcliffe C, Bentley C, Roland CL, Williams SM (2006) Potential differences in breast cancer risk factors based on CYP1A1 MspI and African-American-specific genotypes. Ethn Dis 16:207–215

    PubMed  Google Scholar 

  41. Bailey LR, Roodi N, Verrier CS, Yee CJ, Dupont WD, Parl FF (1998) Breast cancer and CYPIA1, GSTM1, and GSTT1 polymorphisms: evidence of a lack of association in Caucasians and African Americans. Cancer Res 58:65–70

    CAS  PubMed  Google Scholar 

  42. Fontana X, Peyrottes I, Rossi C, Leblanc-Talent P, Ettore F, Namer M, Bussiere F (1998) Study of the frequencies of CYP1A1 gene polymorphisms and glutathione S-transferase mu1 gene in primary breast cancers: an update with an additional 114 cases. Mutat Res 403:45–53

    Article  CAS  PubMed  Google Scholar 

  43. Dialyna IA, Arvanitis DA, Spandidos DA (2001) Genetic polymorphisms and transcriptional pattern analysis of CYP1A1, AhR, GSTM1, GSTP1 and GSTT1 genes in breast cancer. Int J Mol Med 8:79–87

    CAS  PubMed  Google Scholar 

  44. Krajinovic M, Ghadirian P, Richer C, Sinnett H, Gandini S, Perret C, Lacroix A, Labuda D, Sinnett D (2001) Genetic susceptibility to breast cancer in French-Canadians: role of carcinogen-metabolizing enzymes and gene-environment interactions. Int J Cancer 92:220–225

    Article  CAS  PubMed  Google Scholar 

  45. da Fonte de Amorim L, Rossini A, Mendonca G, Lotsch P, de Almeida Simao T, de Moura Gallo C, Pinto L (2002) CYP1A1, GSTM1, and GSTT1 polymorphisms and breast cancer risk in Brazilian women. Cancer Lett 181:179–186

    Article  PubMed  Google Scholar 

  46. Wu FY, Lee YJ, Chen DR, Kuo HW (2002) Association of DNA-protein crosslinks and breast cancer. Mutat Res 501:69–78

    Article  CAS  PubMed  Google Scholar 

  47. Zhu J, Chang P, Bondy ML, Sahin AA, Singletary SE, Takahashi S, Shirai T, Li D (2003) Detection of 2-amino-1-methyl-6-phenylimidazo[4, 5-b]-pyridine-DNA adducts in normal breast tissues and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 12:830–837

    CAS  PubMed  Google Scholar 

  48. Hefler LA, Tempfer CB, Grimm C, Lebrecht A, Ulbrich E, Heinze G, Leodolter S, Schneeberger C, Mueller MW, Muendlein A et al (2004) Estrogen-metabolizing gene polymorphisms in the assessment of breast carcinoma risk and fibroadenoma risk in Caucasian women. Cancer 101:264–269

    Article  CAS  PubMed  Google Scholar 

  49. Zhang Y, Wise JP, Holford TR, Xie H, Boyle P, Zahm SH, Rusiecki J, Zou K, Zhang B, Zhu Y et al (2004) Serum polychlorinated biphenyls, cytochrome P-450 1A1 polymorphisms, and risk of breast cancer in Connecticut women. Am J Epidemiol 160:1177–1183

    Article  PubMed  Google Scholar 

  50. Boyapati SM, Shu XO, Gao YT, Cai Q, Jin F, Zheng W (2005) Polymorphisms in CYP1A1 and breast carcinoma risk in a population-based case-control study of Chinese women. Cancer 103:2228–2235

    Article  CAS  PubMed  Google Scholar 

  51. Chacko P, Joseph T, Mathew BS, Rajan B, Pillai MR (2005) Role of xenobiotic metabolizing gene polymorphisms in breast cancer susceptibility and treatment outcome. Mutat Res 581:153–163

    Article  CAS  PubMed  Google Scholar 

  52. Le Marchand L, Donlon T, Kolonel LN, Henderson BE, Wilkens LR (2005) Estrogen metabolism-related genes and breast cancer risk: the multiethnic cohort study. Cancer Epidemiol Biomarkers Prev 14:1998–2003

    Article  CAS  PubMed  Google Scholar 

  53. Okobia M, Bunker C, Zmuda J, Kammerer C, Vogel V, Uche E, Anyanwu S, Ezeome E, Ferrell R, Kuller L (2005) Cytochrome P4501A1 genetic polymorphisms and breast cancer risk in Nigerian women. Breast Cancer Res Treat 94:285–293

    Article  CAS  PubMed  Google Scholar 

  54. Chang TW, Wang SM, Guo YL, Tsai PC, Huang CJ, Huang W (2006) Glutathione S-transferase polymorphisms associated with risk of breast cancer in southern Taiwan. Breast 15:754–761

    Article  PubMed  Google Scholar 

  55. Shen Y, Li DK, Wu J, Zhang Z, Gao E (2006) Joint effects of the CYP1A1 MspI, ERalpha PvuII, and ERalpha XbaI polymorphisms on the risk of breast cancer: results from a population-based case-control study in Shanghai, China. Cancer Epidemiol Biomarkers Prev 15:342–347

    Article  CAS  PubMed  Google Scholar 

  56. Singh V, Rastogi N, Sinha A, Kumar A, Mathur N, Singh MP (2007) A study on the association of cytochrome-P450 1A1 polymorphism and breast cancer risk in north Indian women. Breast Cancer Res Treat 101:73–81

    Article  CAS  PubMed  Google Scholar 

  57. Singh N, Mitra AK, Garg VK, Agarwal A, Sharma M, Chaturvedi R, Rath SK (2007) Association of CYP1A1 polymorphisms with breast cancer in North Indian women. Oncol Res 16:587–597

    Article  CAS  PubMed  Google Scholar 

  58. Torresan C, Oliveira MM, Torrezan GT, de Oliveira SF, Abuazar CS, Losi-Guembarovski R, Lima RS, Urban CA, Cavalli IJ, Ribeiro EM (2008) Genetic polymorphisms in oestrogen metabolic pathway and breast cancer: a positive association with combined CYP/GST genotypes. Clin Exp Med 8:65–71

    Article  CAS  PubMed  Google Scholar 

  59. Diergaarde B, Potter JD, Jupe ER, Manjeshwar S, Shimasaki CD, Pugh TW, Defreese DC, Gramling BA, Evans I, White E (2008) Polymorphisms in genes involved in sex hormone metabolism, estrogen plus progestin hormone therapy use, and risk of postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev 17:1751–1759

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Li JY, Long QM, Tao P, Hu R, Li H, Lei FM, Zhou WD, Li SF (2008) Using MSR model to analyze the impact of gene-gene interaction with related to the genetic polymorphism of metabolism enzymes on the risk of breast cancer. Sichuan Da Xue Xue Bao Yi Xue Ban 39:780–783 787

    CAS  PubMed  Google Scholar 

  61. Kato I, Cichon M, Yee CL, Land S, Korczak JF (2009) African American-preponderant single nucleotide polymorphisms (SNPs) and risk of breast cancer. Cancer Epidemiol 33:24–30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Sangrajrang S, Sato Y, Sakamoto H, Ohnami S, Laird NM, Khuhaprema T, Brennan P, Boffetta P, Yoshida T (2009) Genetic polymorphisms of estrogen metabolizing enzyme and breast cancer risk in Thai women. Int J Cancer 125:837–843

    Article  CAS  PubMed  Google Scholar 

  63. Shin A, Kang D, Choi JY, Lee KM, Park SK, Noh DY, Ahn SH, Yoo KY (2007) Cytochrome P450 1A1 (CYP1A1) polymorphisms and breast cancer risk in Korean women. Exp Mol Med 39:361–366

    Article  CAS  PubMed  Google Scholar 

  64. Basham VM, Pharoah PD, Healey CS, Luben RN, Day NE, Easton DF, Ponder BA, Dunning AM (2001) Polymorphisms in CYP1A1 and smoking: no association with breast cancer risk. Carcinogenesis 22:1797–1800

    Article  CAS  PubMed  Google Scholar 

  65. Modugno F, Zmuda JM, Potter D, Cai C, Ziv E, Cummings SR, Stone KL, Morin PA, Greene D, Cauley JA (2005) Estrogen metabolizing polymorphisms and breast cancer risk among older white women. Breast Cancer Res Treat 93:261–270

    Article  CAS  PubMed  Google Scholar 

  66. Li JY, Wu DS, Yang F, Zeng HY, Lei FM, Zhou WD, Li H, Tao P (2006) Study on serum organochlorines pesticides (DDTs) level, CYP1A1 genetic polymorphism and risk of breast cancer: a case control study. Zhonghua Liu Xing Bing Xue Za Zhi 27:217–222

    CAS  PubMed  Google Scholar 

  67. Sillanpaa P, Heikinheimo L, Kataja V, Eskelinen M, Kosma VM, Uusitupa M, Vainio H, Metsola K, Hirvonen A (2007) CYP1A1 and CYP1B1 genetic polymorphisms, smoking and breast cancer risk in a Finnish Caucasian population. Breast Cancer Res Treat 104:287–297

    Article  PubMed  Google Scholar 

  68. Gulyaeva LF, Mikhailova ON, PustyInyak VO, Kim IVt, Gerasimov AV, Krasilnikov SE, Filipenko ML, Pechkovsky EV (2008) Comparative analysis of SNP in estrogen-metabolizing enzymes for ovarian, endometrial, and breast cancers in Novosibirsk, Russia. Adv Exp Med Biol 617:359–366

    Article  CAS  PubMed  Google Scholar 

  69. Surekha D, Sailaja K, Rao DN, Padma T, Raghunadharao D, Vishnupriya S (2009) Association of CYP1A1*2 polymorphisms with breast cancer risk: a case control study. Indian J Med Sci 63:13–20

    Article  CAS  PubMed  Google Scholar 

  70. Marks J (1995) Human biodiversity: genes, race, and history. Aldine de Gruyter, New York

    Google Scholar 

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Correspondence to Theodoros N. Sergentanis.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s10549-010-1079-5

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Sergentanis, T.N., Economopoulos, K.P. Four polymorphisms in cytochrome P450 1A1 (CYP1A1) gene and breast cancer risk: a meta-analysis. Breast Cancer Res Treat 122, 459–469 (2010). https://doi.org/10.1007/s10549-009-0694-5

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