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Association between NQO1 C609T polymorphism and acute lymphoblastic leukemia risk: evidence from an updated meta-analysis based on 17 case–control studies

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Abstract

Purpose

Quinone oxidoreductase (NQO1) C609T polymorphisms have been implicated in acute lymphoblastic leukemia (ALL) risk, but previously published studies were inconsistent and recent meta-analyses were not adequate. The aim of this study was to determine more precise estimations for the relationship between the NQO1 C609T polymorphism and the risk of ALL.

Methods

Electronic searches for all publications were conducted on association between this variant and ALL in several databases updated in May 2013. The quality of studies was evaluated using the Newcastle-Ottawa Scale. Crude odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of the association. Seventeen studies were identified, including 2,264 ALL patients and 3,798 controls.

Results

Overall, significantly elevated ALL risk was associated with NQO1 C609T variant genotypes when all of the studies were pooled into the meta-analysis (TT vs. CC: OR 1.46, 95 % CI 1.18–1.79; dominant model: OR 1.45, 95 % CI 1.19–1.77). In the subgroup analysis by ethnicity, significantly increased risks were found for non-Asians (T/T vs. C/C: OR 1.74, 95 % CI 1.29–2.36; dominant model: T/T + C/T vs. C/C: OR 1.7, 95 % CI 1.27–2.29). When stratified by adult or children studies, statistically significantly elevated risks were found among adult studies (codominant model: C/T vs. C/C: OR 1.38, 95 % CI 1.02–1.87; dominant model: T/T + C/T vs. C/C: OR 1.52, 95 % CI 1.18–1.97) and children studies (recessive model: T/T vs. C/T + C/C: OR 1.34, 95 % CI 1.05–1.7).

Conclusions

Our results indicate that the C609T polymorphism of the NQO1 gene is an important genetic risk factor in ALL.

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References

  • Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101

    Article  CAS  PubMed  Google Scholar 

  • Belinsky M, Jaiswal AK (1993) NAD(P)H: quinone oxidoreductase1 (DT-diaphorase) expression in normal and tumor tissues. Cancer Metastasis Rev 12(2):103–117

    Article  CAS  PubMed  Google Scholar 

  • Bolufer P, Barragan E, Collado M, Cervera J, Lopez JA, Sanz MA (2006) Influence of genetic polymorphisms on the risk of developing leukemia and on disease progression. Leuk Res 30(12):1471–1491. doi:10.1016/j.leukres.2006.01.016

    Article  CAS  PubMed  Google Scholar 

  • Bolufer P, Collado M, Barragan E, Cervera J, Calasanz MJ, Colomer D, Roman-Gomez J, Sanz MA (2007) The potential effect of gender in combination with common genetic polymorphisms of drug-metabolizing enzymes on the risk of developing acute leukemia. Haematologica 92(3):308–314

    Article  CAS  PubMed  Google Scholar 

  • Canalle R, Burim RV, Tone LG, Takahashi CS (2004) Genetic polymorphisms and susceptibility to childhood acute lymphoblastic leukemia. Environ Mol Mutagen 43(2):100–109. doi:10.1002/em.20003

    Article  CAS  PubMed  Google Scholar 

  • Chan JY, Ugrasena DG, Lum DW, Lu Y, Yeoh AE (2011) Xenobiotic and folate pathway gene polymorphisms and risk of childhood acute lymphoblastic leukaemia in Javanese children. Hematol Oncol 29(3):116–123. doi:10.1002/hon.965

    Article  CAS  PubMed  Google Scholar 

  • Chao C, Zhang ZF, Berthiller J, Boffetta P, Hashibe M (2006) NAD(P)H: quinone oxidoreductase 1 (NQO1) Pro187Ser polymorphism and the risk of lung, bladder, and colorectal cancers: a meta-analysis. Cancer Epidemiol Biomarkers Prev 15(5):979–987. doi:10.1158/1055-9965.EPI-05-0899

    Article  CAS  PubMed  Google Scholar 

  • Chen H, Lum A, Seifried A, Wilkens LR, Le Marchand L (1999) Association of the NAD(P)H: quinone oxidoreductase 609C– > T polymorphism with a decreased lung cancer risk. Cancer Res 59(13):3045–3048

    CAS  PubMed  Google Scholar 

  • Cho CG, Lee SK, Nam SY, Lee MS, Lee SW, Choi EK, Park HJ, Kim SY (2006) Association of the GSTP1 and NQO1 polymorphisms and head and neck squamous cell carcinoma risk. J Korean Med Sci 21(6):1075–1079

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Clavel J, Bellec S, Rebouissou S, Menegaux F, Feunteun J, Bonaiti-Pellie C, Baruchel A, Kebaili K, Lambilliotte A, Leverger G, Sommelet D, Lescoeur B, Beaune P, Hemon D, Loriot MA (2005) Childhood leukaemia, polymorphisms of metabolism enzyme genes, and interactions with maternal tobacco, coffee and alcohol consumption during pregnancy. Eur J Cancer Prev 14(6):531–540

    Article  PubMed  Google Scholar 

  • Cochran WG (1950) The comparison of percentages in matched samples. Biometrika 37(3–4):256–266

    Article  CAS  PubMed  Google Scholar 

  • de Aguiar Goncalves BA, Vasconcelos GM, Thuler LC, Andrade C, Faro A, Pombo-de-Oliveira MS, Emerenciano M, de Camargo B, Bernstain L, Neves CC, Agareno JM, de Carvalho LM, Araujo FN, de Brito NP, Magalhaes IQ, Cordoba JC, Pimenta F, Gadelha A, Cartaxo E, Basegio RM, Mnayarji A, Souza MS, Arencibia A, Melaragno R, Coser VM, Lafayete TC, Koifman S (2012) NQO1 rs1800566 (C609T), PON1 rs662 (Q192R), and PON1 rs854560 (L55 M) polymorphisms segregate the risk of childhood acute leukemias according to age range distribution. Cancer Causes Control 23(11):1811–1819. doi:10.1007/s10552-012-0060-5

    Article  PubMed  Google Scholar 

  • DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188

    Article  CAS  PubMed  Google Scholar 

  • Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Farhad Z, Safaei A, Nasiri N, Abdollahzadeh M, Pazhakh V (2012) The Association of NAD(P)H: quinine oxidoreductase gene polymorphisms with pediatric acute lymphoblastic leukemia. Science 43(6):256–261

    Google Scholar 

  • Guha N, Chang JS, Chokkalingam AP, Wiemels JL, Smith MT, Buffler PA (2008) NQO1 polymorphisms and de novo childhood leukemia: a HuGE review and meta-analysis. Am J Epidemiol 168(11):1221–1232. doi:10.1093/aje/kwn246

    Article  PubMed Central  PubMed  Google Scholar 

  • Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560. doi:10.1136/bmj.327.7414.557

    Article  PubMed Central  PubMed  Google Scholar 

  • Infante-Rivard C, Vermunt JK, Weinberg CR (2007) Excess transmission of the NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T polymorphism in families of children with acute lymphoblastic leukemia. Am J Epidemiol 165(11):1248–1254. doi:10.1093/aje/kwm022

    Article  PubMed Central  PubMed  Google Scholar 

  • Jia MF, Xi YM, Shi XE, Zhang H, Deng W, Li M, Li P, Xu JW, Ma HZ, Yao XJ (2012) Relationship of MPO and NQO1 gene polymorphisms with susceptibility to acute leukemia. Zhongguo Shi Yan Xue Ye Xue Za Zhi 20(6):1336–1340

    CAS  PubMed  Google Scholar 

  • Kracht T, Schrappe M, Strehl S, Reiter A, Elsner HA, Trka J, Cario G, Viehmann S, Harbott J, Borkhardt A, Metzler M, Langer T, Repp R, Marschalek R, Welte K, Haas OA, Stanulla M (2004) NQO1 C609T polymorphism in distinct entities of pediatric hematologic neoplasms. Haematologica 89(12):1492–1497

    CAS  PubMed  Google Scholar 

  • Krajinovic M, Labuda D, Sinnett D (2001) Childhood acute lymphoblastic leukemia: genetic determinants of susceptibility and disease outcome. Rev Environ Health 16(4):263–279

    Article  CAS  PubMed  Google Scholar 

  • Krajinovic M, Sinnett H, Richer C, Labuda D, Sinnett D (2002) Role of NQO1, MPO and CYP2E1 genetic polymorphisms in the susceptibility to childhood acute lymphoblastic leukemia. Int J Cancer 97(2):230–236

    Article  CAS  PubMed  Google Scholar 

  • Kuehl BL, Paterson JW, Peacock JW, Paterson MC, Rauth AM (1995) Presence of a heterozygous substitution and its relationship to DT-diaphorase activity. Br J Cancer 72(3):555–561

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lanciotti M, Dufour C, Corral L, Di Michele P, Pigullo S, De Rossi G, Basso G, Leszl A, Luciani M, Lo Nigro L, Micalizzi C, Valsecchi MG, Biondi A, Haupt R (2005) Genetic polymorphism of NAD(P)H: quinone oxidoreductase is associated with an increased risk of infant acute lymphoblastic leukemia without MLL gene rearrangements. Leukemia 19(2):214–216. doi:10.1038/sj.leu.2403613

    Article  CAS  PubMed  Google Scholar 

  • Larfors G, Hallbook H, Simonsson B (2012) Parental age, family size, and offspring’s risk of childhood and adult acute leukemia. Cancer Epidemiol Biomarkers Prev 21(7):1185–1190. doi:10.1158/1055-9965.EPI-12-0178

    Article  PubMed  Google Scholar 

  • Larson RA, Wang Y, Banerjee M, Wiemels J, Hartford C, Le Beau MM, Smith MT (1999) Prevalence of the inactivating 609C– > T polymorphism in the NAD(P)H: quinone oxidoreductase (NQO1) gene in patients with primary and therapy-related myeloid leukemia. Blood 94(2):803–807

    CAS  PubMed  Google Scholar 

  • Li H, Hao X, Zhang W, Wei Q, Chen K (2008) The hOGG1 Ser326Cys polymorphism and lung cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev 17(7):1739–1745. doi:10.1158/1055-9965.EPI-08-0001

    Article  PubMed  Google Scholar 

  • MacArthur AC, McBride ML, Spinelli JJ, Tamaro S, Gallagher RP, Theriault G (2008) Risk of childhood leukemia associated with parental smoking and alcohol consumption prior to conception and during pregnancy: the cross-Canada childhood leukemia study. Cancer Causes Control 19(3):283–295. doi:10.1007/s10552-007-9091-8

    Article  PubMed  Google Scholar 

  • Moran JL, Siegel D, Ross D (1999) A potential mechanism underlying the increased susceptibility of individuals with a polymorphism in NAD(P)H: quinone oxidoreductase 1 (NQO1) to benzene toxicity. Proc Natl Acad Sci U S A 96(14):8150–8155

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nebert DW, Roe AL, Vandale SE, Bingham E, Oakley GG (2002) NAD(P)H: quinone oxidoreductase (NQO1) polymorphism, exposure to benzene, and predisposition to disease: a HuGE review. Genet Med 4(2):62–70. doi:http://www.indexscholar.com/?record=1207241

    Article  CAS  PubMed  Google Scholar 

  • Ouerhani S, Cherif N, Bahri I, Safra I, Menif S, Abbes S (2013) Genetic polymorphisms of NQO1, CYP1A1 and TPMT and susceptibility to acute lymphoblastic leukemia in a Tunisian population. Mol Biol Rep 40(2):1307–1314. doi:10.1007/s11033-012-2174-y

    Article  CAS  PubMed  Google Scholar 

  • Perera FP (1997) Environment and cancer: who are susceptible? Science 278(5340):1068–1073

    Article  CAS  PubMed  Google Scholar 

  • Radjendirane V, Joseph P, Lee YH, Kimura S, Klein-Szanto AJ, Gonzalez FJ, Jaiswal AK (1998) Disruption of the DT diaphorase (NQO1) gene in mice leads to increased menadione toxicity. J Biol Chem 273(13):7382–7389

    Article  CAS  PubMed  Google Scholar 

  • Rimando M, Yuson ED, de Castro-Bernas G, Okamoto T (2008) Prevalence of GSTT1, GSTM1 and NQO1(609C > T) in filipino children with ALL(acute lymphoblastic leukaemia). Biosci Rep 28(3):117–124

    Article  CAS  PubMed  Google Scholar 

  • Sameer AS, Shah ZA, Syeed N, Rasool R, Afroze D, Siddiqi MA (2010) NAD(P)H: quinone oxidoreductase 1 (NQO1) Pro187Ser polymorphism and colorectal cancer predisposition in the ethnic Kashmiri population. Asian Pac J Cancer Prev 11(1):209–213

    PubMed  Google Scholar 

  • Schulz WA, Krummeck A, Rosinger I, Eickelmann P, Neuhaus C, Ebert T, Schmitz-Drager BJ, Sies H (1997) Increased frequency of a null-allele for NAD(P)H: quinone oxidoreductase in patients with urological malignancies. Pharmacogenetics 7(3):235–239

    Article  CAS  PubMed  Google Scholar 

  • Shields PG, Harris CC (2000) Cancer risk and low-penetrance susceptibility genes in gene-environment interactions. J Clin Oncol 18(11):2309–2315

    CAS  PubMed  Google Scholar 

  • Siegel D, Ryder J, Ross D (2001) NAD(P)H: quinone oxidoreductase 1 expression in human bone marrow endothelial cells. Toxicol Lett 125(1–3):93–98

    Article  CAS  PubMed  Google Scholar 

  • Silveira Vda S, Canalle R, Scrideli CA, Queiroz RG, Tone LG (2010) Role of the CYP2D6, EPHX1, MPO, and NQO1 genes in the susceptibility to acute lymphoblastic leukemia in Brazilian children. Environ Mol Mutagen 51(1):48–56. doi:10.1002/em.20510

    PubMed  Google Scholar 

  • Sirma S, Agaoglu L, Yildiz I, Cayli D, Horgusluoglu E, Anak S, Yuksel L, Unuvar A, Celkan T, Apak H, Karakas Z, Devecioglu O, Ozbek U (2004) NAD(P)H:quinone oxidoreductase 1 null genotype is not associated with pediatric de novo acute leukemia. Pediatr Blood Cancer 43(5):568–570. doi:10.1002/pbc.20098

    Article  PubMed  Google Scholar 

  • Smith MT (1999) Benzene, NQO1, and genetic susceptibility to cancer. Proc Natl Acad Sci U S A 96(14):7624–7626

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Smith MT, Wang Y, Kane E, Rollinson S, Wiemels JL, Roman E, Roddam P, Cartwright R, Morgan G (2001) Low NAD(P)H:quinone oxidoreductase 1 activity is associated with increased risk of acute leukemia in adults. Blood 97(5):1422–1426

    Article  CAS  PubMed  Google Scholar 

  • Spector TD, Thompson SG (1991) The potential and limitations of meta-analysis. J Epidemiol Community Health 45(2):89–92

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Strange RC, Spiteri MA, Ramachandran S, Fryer AA (2001) Glutathione-S-transferase family of enzymes. Mutat Res 482(1–2):21–26

    Article  CAS  PubMed  Google Scholar 

  • Strassburg A, Strassburg CP, Manns MP, Tukey RH (2002) Differential gene expression of NAD(P)H:quinone oxidoreductase and NRH: quinone oxidoreductase in human hepatocellular and biliary tissue. Mol Pharmacol 61(2):320–325

    Article  CAS  PubMed  Google Scholar 

  • Traver RD, Horikoshi T, Danenberg KD, Stadlbauer TH, Danenberg PV, Ross D, Gibson NW (1992) NAD(P)H: quinone oxidoreductase gene expression in human colon carcinoma cells: characterization of a mutation which modulates DT-diaphorase activity and mitomycin sensitivity. Cancer Res 52(4):797–802

    CAS  PubMed  Google Scholar 

  • Vijayakrishnan J, Houlston RS (2010) Candidate gene association studies and risk of childhood acute lymphoblastic leukemia: a systematic review and meta-analysis. Haematologica 95(8):1405–1414. doi:10.3324/haematol.2010.022095

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yamaguti GG, Lourenco GJ, Silveira VS, Tone LG, Lopes LF, Lima CS (2010) Increased risk for acute lymphoblastic leukemia in children with cytochrome P450A1 (CYP1A1)- and NAD(P)H: quinone oxidoreductase 1 (NQO1)-inherited gene variants. Acta Haematol 124(3):182–184. doi:10.1159/000320275

    Article  PubMed  Google Scholar 

  • Yeoh AE, Lu Y, Chan JY, Chan YH, Ariffin H, Kham SK, Quah TC (2010) Genetic susceptibility to childhood acute lymphoblastic leukemia shows protection in Malay boys: results from the Malaysia-Singapore ALL Study Group. Leuk Res 34(3):276–283. doi:10.1016/j.leukres.2009.07.003

    Article  CAS  PubMed  Google Scholar 

  • Zhang ZQ, Yang L, Zhang Y, Yang YH, Nie L, Li L, Wang JX, Zhu XF, Xiao ZJ (2009) Relationship between NQO1C(609T), RAD51(G135C), XRCC3(C241T) single nucleotide polymorphisms and acute lymphoblastic leukemia. Zhongguo Shi Yan Xue Ye Xue Za Zhi 17(3):523–528

    PubMed  Google Scholar 

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Acknowledgments

We are thankful to all participants of our study. This study was supported by no grants. Two investigators (Cuiping Li and Yang Zhou) searched the initially relevant literature and extracted data from each eligible case–control study independently to ensure the accuracy of data. Cuiping Li is responsible for writing this article. Yang Zhou determines the article accurately and submits a piece of writing for publication.

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We declare that we have no conflict of interest.

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  1. School of Public Health, Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China

    Cuiping Li & Yang Zhou

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Correspondence to Yang Zhou.

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Li, C., Zhou, Y. Association between NQO1 C609T polymorphism and acute lymphoblastic leukemia risk: evidence from an updated meta-analysis based on 17 case–control studies. J Cancer Res Clin Oncol 140, 873–881 (2014). https://doi.org/10.1007/s00432-014-1595-5

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