Polymorphisms in xenobiotic metabolizing genes (EPHX1, NQO1 and PON1) in lymphoma susceptibility: a case control study

BMC Cancer

Miguel Pérez-Guillermo⁴  Vicente Vicente³  Javier Corral¹  Rocío González-Conejero¹  Elena Pérez-Ceballos³  Javier Trujillo-Santos⁵  María D Gutiérrez-Meca²  Ignacio Español²  Daniel Torres-Moreno⁴  Javier Ruiz-Cosano⁴  Pablo Conesa-Zamora⁴ 

[1]Department of Medicine, Centro Regional de Hemodonación, 30003, Murcia, Spain

[2]Haematology Department. (HGUSL), 30202, Cartagena, Spain

[3]Haematology Department, Morales Meseguer University Hospital (HGUMM), Murcia, Spain

[4]Molecular Pathology and Pharmacogenetic Group. Pathology Department, Santa Lucía General University Hospital (HGUSL), 30202, Cartagena, Spain

[5]Internal Medicine Department. (HGUSL), 30202, Cartagena, Spain

关键词: Susceptibility;    Lymphoma;    SNP;    Polymorphism;    EPHX1;    NQO1;    PON1;   

Others  :  1079763
DOI  :  10.1186/1471-2407-13-228

 received in 2012-09-24, accepted in 2013-05-01,  发布年份 2013

【 摘 要 】

Background

The interplay between genetic susceptibility and carcinogenic exposure is important in the development of haematopoietic malignancies. EPHX1, NQO1 and PON1 are three genes encoding proteins directly involved in the detoxification of potential carcinogens.

Methods

We have studied the prevalence of three functional polymorphisms affecting these genes rs1051740 EPHX1, rs1800566 NQO1 and rs662 PON1 in 215 patients with lymphoma and 214 healthy controls.

Results

Genotype frequencies for EPHX and NQO1 polymorphisms did not show any correlation with disease. In contrast, the GG genotype in the PON1 polymorphism was found to be strongly associated with the disease (15.3% vs. 4.7%; OR = 3.7 CI (95%): 1.8-7.7; p < 0.001). According to the pathological diagnosis this association was related to follicular (p = 0.004) and diffuse large B-cell (p = 0.016) lymphomas.

Conclusions

Despite the fact that further confirmation is needed, this study shows that the PON1 GG genotype in rs662 polymorphism could be a risk factor for B-cell lymphomas.

【 授权许可】

   
2013 Conesa-Zamora et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Shimada T: Xenobiotic-Metabolizing Enzymes involved in Activation and Detoxification of Carcinogenic Polycyclic Aromatic Hydrocarbons. Drug Metab Pharmacokinet 2006, 21:257-276.
• [2]Rose RL, Hodgson E: Adaptation to Toxicants. Chemical and Environmental Factors Affecting Metabolism of Xenobiotics. In Introduction to biochemical toxicology. Edited by Hodgson E, Smart RC. New York: Willey; 2001:163-198.
• [3]Fritschi L, Benke G, Hughes AM: Occupational Exposure to Pesticides and Risk of Non-Hodgkin’s Lymphoma. Am J Epidemiol 2005, 162:849-857.
• [4]Roulland S, Lebailly P, Lecluse Y: Characterization of the t(14;18) BCL2-IGH translocation in farmers occupationally exposed to pesticides. Cancer Res 2004, 64:2264-2269.
• [5]Wong O, Fue H: Exposure to benzene and non-Hodgkin lymphoma, an epidemiologic overview and an ongoing case–control study in Shanghai. Chem Biol Interact 2005, 153–154:33-41.
• [6]Fritschi L, Benke G, Hughes AM: Risk of non-Hodgkin lymphoma associated with occupational exposure to solvents, metals, organic dusts and PCBs (Australia). Cancer Causes Control 2005, 16:599-607.
• [7]Lamm SH, Engel A, Byrd DM: Non-Hodgkin lymphoma and benzene exposure: a systematic literature review. Chem Biol Interact 2005, 153–154:231-237.
• [8]De Roos AJ, Gold LS, Wang S: Metabolic gene variants and risk of non-Hodgkin’s lymphoma. Cancer Epidemiol Biomarkers Prev 2006, 15:1647-1653.
• [9]Kerridge I, Lincz L, Scorgie F, Hickey D, Granter N, Spencer A: Association between xenobiotic gene polymorphisms and non-Hodgkin’s lymphoma risk. Br J Haematol 2002, 118:477-481.
• [10]Sarmanova J, Benesova K, Gut I, Nedelcheva-Kristensen V, Tynkova L, Soucek P: Genetic polymorphisms of biotransformation enzymes in patients with Hodgkin’s and non-Hodgkin’s lymphomas. Hum Molec Genet 2001, 10:1265-1273.
• [11]Barry KH, Zhang Y, Lan Q: Genetic variation in metabolic genes, occupational solvent exposure, and risk of non-hodgkin lymphoma. Am J Epidemiol 2011, 173:404-413.
• [12]Infante-Rivard C, Vermunt JK, Weinberg CR: Excess transmission of the NAD(P)H:quinone oxidoreductase 1 (NQO1) C609T polymorphism in families of children with acute lymphoblastic leukemia. Am J Epidemiol 2007, 165:1248-1254.
• [13]Infante-Rivard C, Labuda D, Krajinovic M, Sinnett D: Risk of childhood leukemia associated with exposure to pesticides and with gene polymorphisms. Epidemiology 1999, 10:481-487.
• [14]Swerdlow SH, Campo E, Harris NL: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2008.
• [15]Ruiz-Cosano J, Conesa-Zamora P, González-Conejero R: Role of GSTT1 and M1 null genotypes as risk factors for B-cell lymphoma: influence of geographical factors and occupational exposure. Mol Carcinog 2012, 51:508-513.
• [16]García-Pérez J, Boldo E, Ramis R: Description of industrial pollution in Spain. BMC Public Health 2007, 7:40. BioMed Central Full Text
• [17]Cirera L, Rodríguez M, Giménez J: Effects of public health interventions on industrial emissions and ambient air in Cartagena, Spain. Environ Sci Pollut Res Int 2009, 16:152-161.
• [18]Real D: 1197/1979 de 20 de Febrero, por el que se declara aplicable a parte del término municipal de Cartagena (Murcia) las medidas y beneficios previstos en la Ley 38/1972 de Diciembre, y Reglamentación complementaria de protección del ambiente atmosférico]. Spanish Government Official Bulletin (BOE) 1979, 123:11406.
• [19]López-Abente G, Hernández-Barrera V, Pollán M: Municipal pleural cancer mortality in Spain. Occup Environ Med 2005, 62:195-199.
• [20]Lopez-Abente G, Aragones N, Ramis R: Municipal distribution of bladder cancer mortality in Spain: possible role of mining and industry. BMC Public Health 2006, 6:17. BioMed Central Full Text
• [21]Gauderman WJ, Morrison JM: QUANTO 1.1: A Computer program for power and sample size calculations for genetic-epidemiology studies. 2006. http://hydra.usc.edu/gxe webcite
• [22]Li Z, Zhang Z, He Z, Tang W, Li T, Zeng Z, He L, Shi Y: A partition-ligation-combination-subdivision EM algorithm for haplotype inference with multiallelic markers: update of the SHEsis (http://analysis.bio-x.cn webcite). Cell Res 2009, 19:519-523.
• [23]Hassett C, Aicher L, Sidhu JS, Omiecinski CJ: Human microsomal epoxide hydrolase: genetic polymorphism and functional expression in vitro of amino acid variants. Hum Molec Genet 1994, 3:421-428.
• [24]Tumer TB, Sahin G, Arinç E: Association between polymorphisms of EPHX1 and XRCC1 genes and the risk of childhood acute lymphoblastic leukemia. Arch Toxicol 2012, 86:431-439.
• [25]Silveira Vda S, Canalle R, Scrideli CA, Queiroz RG, Tone LG: Role of the CYP2D6, EPHX1, MPO, and NQO1 genes in the susceptibility to acute lymphoblastic leukemia in Brazilian children. Environ Mol Mutagen 2010, 51:48-56.
• [26]Chauhan PS, Ihsan R, Mishra AK, Yadav DS, Saluja S, Mittal V: High order interactions of xenobiotic metabolizing genes and P53 codon 72 polymorphisms in acute leukemia. Environ Mol Mutagen 2012, 53:619-630.
• [27]da Silva SV, Canalle R, Scrideli CA, Queiroz RG, Bettiol H, Valera ET: Polymorphisms of xenobiotic metabolizing enzymes and DNA repair genes and outcome in childhood acute lymphoblastic leukemia. Leuk Res 2009, 33:898-901.
• [28]Moran JL, Siegel D, Ross D: A potential mechanism underlying the increased susceptibility of individuals with a polymorphism in NAD(P)H:quinone oxidoreductase 1 (NQO1) to benzene toxicity. Proc Nat Acad Sci 1999, 96:8150-8155.
• [29]Rothman N, Smith MT, Hayes RB: Benzene poisoning, a risk factor for hematological malignancy, is associated with the NQO1 609C-T mutation and rapid fractional excretion of chlorzoxazone. Cancer Res 1997, 57:2839-2842.
• [30]Chan JY, Ugrasena DG, Lum DW, Lu Y, Yeoh AE: Xenobiotic and folate pathway gene polymorphisms and risk of childhood acute lymphoblastic leukaemia in Javanese children. Hematol Oncol 2011, 29:116-123.
• [31]Krajinovic M, Sinnett H, Richer C, Labuda D, Sinnett D: Role of NQO1, MPO and CYP2E1 genetic polymorphisms in the susceptibility to childhood acute lymphoblastic leukemia. Int J Cancer 2002, 97:230-236.
• [32]Stanulla M, Dynybil C, Bartels DB, Dördelmann M, Löning L, Claviez A: The NQO1 C609T polymorphism is associated with risk of secondary malignant neoplasms after treatment for childhood acute lymphoblastic leukemia: a matched-pair analysis from the ALL-BFM study group. Haematologica 2007, 92:1581-1582.
• [33]Guha N, Chang JS, Chokkalingam AP, Wiemels JL, Smith MT, Buffler PA: NQO1 polymorphisms and de novo childhood leukemia: a HuGE review and meta-analysis. Am J Epidemiol 2008, 168:1221-1232.
• [34]Eguchi-Ishimae M, Eguchi M, Ishii E, Knight D, Sadakane Y, Isoyama K: The association of a distinctive allele of NAD(P)H:quinine oxidoreductase with pediatric acute lymphoblastic leukemias with MLL fusion genes in Japan. Haematologica 2005, 90:1511-1515.
• [35]Sirma S, Agaoglu L, Yildiz I, Cayli D, Horgusluoglu E, Anak S: NAD(P)H:quinine oxidoreductase 1 null genotype is not associated with pediatric de novo acute leukemia. Pediatr Blood Cancer 2004, 43:568-570.
• [36]Draganov DI, Teiber JF, Speelman A, Osawa Y, Sunahara R, La Du BN: Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities. J Lipid Res 2005, 46:1239-1247.
• [37]Humbert R, Adler DA, Disteche CM, Hassett C, Omiecinski CJ, Furlong CE: The molecular basis of the human serum paraoxonase activity polymorphism. Nature Genet 1993, 3:73-76.
• [38]Kokouva M, Koureas M, Dardiotis E, Almpanidou P, Kalogeraki A, Kyriakou D: Relationship between the paraoxonase 1 (PON1) M55L and Q192R polymorphisms and lymphohaematopoietic cancers in a Greek agricultural population. Toxicology 2012. in press
• [39]Conde L, Halperin E, Akers NK, Brown KM, Smedby KE, Rothman N: Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32. Nat Genet 2010, 42:661-4.
• [40]Smedby KE, Foo JN, Skibola CF, Darabi H, Conde L, Hjalgrim H: GWAS of follicular lymphoma reveals allelic heterogeneity at 6p21.32 and suggests shared genetic susceptibility with diffuse large B-cell lymphoma. PLoS Genet 2011, 7:e1001378.
• [41]Skibola CF, Bracci PM, Halperin E, Conde L, Craig DW, Agana L: Genetic variants at 6p21.33 are associated with susceptibility to follicular lymphoma. Nat Genet 2009, 41:873-5.
• [42]Vijai J, Kirchhoff T, Schrader KA, Brown J, Dutra-Clarke AV, Manschreck C: Susceptibility loci associated with specific and shared subtypes of lymphoid malignancies. PLoS Genet 2013, 9:e1003220.