Investigation of CYP1B1*3 and CYP1B1*4 polymorphisms in a Turkish population

Fatma Özlem Solmaz Kargın; Jale Akgöl; Merve Becit Kızılkaya; Ahmet Oğuz Ada

doi:10.26900/hsq.2.3.02

Authors

Fatma Özlem Solmaz Kargın Afyonkarahisar Health Sciences University / Türkiye 0000-0002-3908-3371
Jale Akgöl Afyonkarahisar Health Sciences University / Türkiye 0000-0002-9163-3991
Merve Becit Kızılkaya Afyonkarahisar Health Sciences University / Türkiye 0000-0002-8084-4419
Ahmet Oğuz Ada Ankara University / Türkiye 0000-0001-9987-0572

10.26900/hsq.2.3.02

Abstract

CYP1B1 is a P450 enzyme involved in activating pro-carcinogens to carcinogens as well as estrogen metabolism. In order to examine the effect of CYP1B1 on cancer metabolism, it should be compared with healthy individuals and whether the polymorphism between healthy individuals and sick individuals is significant. This study aims to screen the CYP1B1*3 and CYP1B1*4 polymorphisms of a group of individuals who have not been diagnosed with cancer to examine the genetic differences of metabolic enzymes in the Turkish population.This study is a cross-sectional type descriptive study.The study included 295 patients without a cancer diagnosis. The research sample includes patients who applied to Ankara University Medical Faculty Hospital and Afyonkarahisar Health Sciences University Research and Application Hospital. The individuals signed voluntary consent forms before participation, and 3 ml blood samples were taken from each. DNA samples were obtained using a DNA isolation kit, and then polymorphism was determined by real-time PCR. The distribution of CYP1B1*3 and CYP1B1*4 polymorphism in healthy individuals was determined. The frequency of CYP1B1*1/*1 (wild type), CYP1B1*1/*3 (heterozygous) and, CYP1B1*3/*3 (mutant) genotypes were found 39.33%, 50.67% and 10.0% respectively. The frequency of CYP1B1*1/*1 (wild type), CYP1B1*1/*4 (heterozygous) and, CYP1B1*4/*4 (mutant) genotypes were found 39.31%, 60.69% and 0% respectively. No individuals with mutant genotype were detected in this genotype (CYP1B1*4).The results show that the genotype frequencies of the CYP1B1*3 gene polymorphism in a Turkish population are similar to other Caucasian populations. However, it was determined that the Turkish population did not show similarity with other races in terms of CYP1B1*4 polymorphism.

Keywords:

CYP1B1 polymorphism rs1056836 rs1800440 Turkish population

Downloads

Download data is not yet available.

References

Abdul Aziz AA, Md Salleh MS, Yahya MM, Zakaria AD, Ankathil R. Genetic association of CYP1B1 4326 C>G polymorphism with disease-free survival in TNBC patients undergoing TAC chemotherapy regimen. APJCP.2021;22(4):1319-24. doi: 10.31557/APJCP.2021.22.4.1319.

Faiq MA, Ali M, Dada T, Dada R, Saluja D. A novel methodology for enhanced and consistent heterologous expression of unmodified human cytochrome P450 1B1 (CYP1B1). PLoS One. 2014;9(10):e110473.

Sutter TR, Tang YM, Hayes CL, Wo YY, Jabs EW, Li X, et al. Complete cDNA sequence of a human dioxin-inducible mRNA identifies a new gene subfamily of cytochrome P450 that maps to chromosome 2.J Biol Chem. 1994;269(18):13092-9.

Tang YM, Wo YY, Stewart J, Hawkins AL, Griffin CA, Sutter TR, et al. Isolation and characterization of the human cytochrome P450 CYP1B1 gene. J Biol Chem. 1996;271(45):28324-30. doi: 10.1074/jbc.271.45.28324.

Zhang H, Li L, Xu Y. CYP1B1 polymorphisms and susceptibility to prostate cancer: A meta analysis. PLoS One. 2013;8(7):68634. doi: 10.1371/journal.pone.0068634.

Ada AO, Kunak CS, Hancer F, Bilgen S, Suzen SH,Alpar S, et al. CYP and GST polymorphisms and survival in advanced non-small-cell lung cancer patients. Neoplasma. 2010;57(6):512-21. doi: 10.4149/neo_2010_06_512.

Agundez, J.A. Cytochrome P450 gene polymorphism and cancer. Curr Drug Metab.2004;5(3):211-24. doi: 10.2174/1389200043335621.

McFadyen MC, Cruickshank ME, Miller ID, McLeod HL, Melvin WT, Haites NE, et al. Cytochrome P450 CYP1B1 over-expression in primary and metastatic ovarian cancer. Br J Cancer. 2001;85(2):242-46. doi: 10.1054/bjoc.2001.1907.

Xu X, Ong YK, Wang DY. Role of adjunctive treatment strategies in COVID-19 and a review of international and national clinical guidelines. Mil Med Res. 2020;7(1):22. doi: 10.1186/s40779 020- 00251-x.

Ada AO, Demiroglu C, Yilmazer M, Suzen HS, Demirbag AE, Efe S, et al. Cytogenetic damage in Turkish coke oven workers exposed to polycyclic aromatic hydrocarbons: Association with CYP1A1, CYP1B1, EPHX1, GSTM1, GSTT1, and GSTP1 gene polymorphisms. Arh Hig Rada Toksikol. 2013;64(3):359-69. doi: 10.2478/10004-1254-64-2013-2328.

Güler A. The role of metabolic (CYP1B1) polymorphism in drug resistance in lung cancer, in Pharmacy and Pharmacology. PhD, Ankara Üniversitesi, Ankara, 2019.

Özbek YK, Öztürk T, Tüzüner BM, Clay Z, Ilvan S, Seyhan FM, et al. Combined effect of CYP1B1 codon 432 polymorphism and N-acetyltransferase 2 slow acetylator phenotypes in relation to breast cancer in the Turkish population. Anticancer Res.2010;30(7):2885-89.

Zanger UM, Schwab M. Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther. 2013;138(1):103- 41. doi: 10.1016/j.pharmthera.2012.12.007.

Aklillu E, Oscarson M, Hidestrand M, Leidvik B, Otter C, Ingelman-Sundberg M. Functional analysis of six different polymorphic CYP1B1 enzyme variants found in an Ethiopian population. Mol Pharmacol. 2002;61(3):586-94. doi: 10.1124/mol.61.3.586.

B-Rao C. Sample size considerations in genetic polymorphism studies. Hum Hered. 2001;52(4):191-00. doi: 10.1159/000053376.

Miller JH. Mutators in Escherichia coli. Mutat Res. 1998;409(3):99-106. doi:10.1016/s0921-8777(98)00049-4.

Bünning T, Abel J, Koch B, Lorenzen K, Harth V, Donat S, et al. Real-time PCR-analysis of the cytochrome P450 1B1 codon 432-polymorphism. Arch Toxicol. 1999;73(8-9):427-30 doi: 10.1016/j. tox.2004.08.021.

Bilgen S. Akciğer Kanserinde Metabolik (Cyp1) Polimorfizminin İlaç Rezistansindaki Rolü. PhD, Ankara Üniversitesi, Ankara, 2008.

Martinez AG, Loria BG, Tejero ME, Sierra-Santoyo A, Cebrian ME, Lopez-Carrillo L. CYP1A1, CYP1B1, GSTM1 and GSTT1 genetic variants and breast cancer risk in Mexican women. Salud pública Mex. 2017;59:5. doi: 10.21149/8527.

Delort L, Satih S, Kwiatkowski F, Bignon YJ, Bernard-Gallon DJ. Evaluation of breast cancer risk in a multigenic model including low penetrance genes involved in xenobiotic and estrogen metabolisms. Nutr Cancer. 2010;62(2):243-51. doi: 10.1080/01635580903305300.

Shah PP, Singh AP, Singh M, Mathur N, Mishra BN, Pant MC, et al. Association of functionally important polymorphisms in cytochrome P4501B1 with lung cancer. Mutat Res. 2008;643(1- 2):4-10. doi: 10.1016/j.mrfmmm.2008.05.001.

Soucek P, Susova S, Mohelkinova- Duchonova B, Gromadzinska J, Moraviec-Sztandera A, Vodicka P, et al. Polymorphisms in metabolizing enzymes and the risk of head and neck squamous cell carcinoma in the Slavic population of the central Europe. Neoplasma. 2010;57(5):415-21. doi: 10.4149/neo_2010_05_415.

Tai J, Yang M, Ni X, Yu D, Fang J, Tan W, et al. Genetic polymorphisms in cytochrome P450 genes are associated with an increased risk of squamous cell carcinoma of the larynx and hypopharynx in a Chinese population. Cancer Genet Cytogenet. 2010;196(1):76-82. doi: 10.1016/j. cancergencyto.2009.08.015.

Harth V, Schafer M, Abel J, Maintz L, Neuhaus T, Besuden M, et al. Head and neck squamous cell cancer and its association with polymorphic enzymes of xenobiotic metabolism and repair. J Toxicol Environ Health. 2008;71(13-14):887-97. doi: 10.1080/15287390801988160.

Sigh AP, Shah P, Mathur N, Buters JTM, Pant M, et al. Genetic polymorphisms in cytochrome P4501B1 and susceptibility to head and neck cancer. Mutat Res. 2008;639(1-2):11 9. doi: 10.1016/j.mrfmmm.2007.10.007.

Li G, Liu Z, Sturgis EM, Chamberlain RM, Spitz MR, Wei Q. CYP2E1 G1532C, NQO1 Pro187Ser, and CYP1B1 Val432Leu polymorphisms are not associated with risk of squamous cell carcinoma of the head and neck. Cancer Epidemiol Biomarkers Prev. 2005;14(4):1034-6. doi: 10.1158/1055-9965.EPI-04-0814.

Landi MT, Bergen AW, Baccarelli A, Patterson DG, Grassman J, Ter-Minassian M, et al.CYP1A1 and CYP1B1 genotypes, haplotypes, and TCDDinduced gene expression in subjects from Seveso, Italy. Toxicology. 2005;14;207(2):191-02. doi: 10.1016/j.tox.2004.08.021.

Bethke L, Webb E, Sellick G, Rudd M, Penegar S, Withey L, et al. Polymorphisms in the cytochrome P450 genes CYP1A2, CYP1B1, CYP3A4, CYP3A5, CYP11A1, CYP17A1,CYP19A1and colorectal cancer risk. BMC Cancer. 2007;5(7):123. doi: 10.1186/1471-2407-7-123.

Ashton KA, Proietto A, Otton G, Symonds I,McEvoy M, Attia J, et al. Polymorphisms in genes of the steroid hormone biosynthesis and metabolism pathways and endometrial cancer risk. Cancer Epidemiol. 2010; 34(3):328-37. doi: 10.1016/j.canep.2010.03.005.

Chang BL, Zheng SL, Isaacs SD, Turner A, Hawkins GA, Wiley KE, et al. Polymorphisms in the CYP1B1 gene are associated with increased risk of prostate cancer. Br J Cancer. 2003;20(89):1524-9. doi: 10.1038/s.bjc.6601288.

Sasaki M, Tanaka Y, Okino ST, Nomoto M, Yonezawa S, Nakagawa M, et al. Polymorphisms of the CYP1B1 gene as risk factors for human renal cell cancer. Clin Cancer Res. 2004;10(6):2015- 9. doi: 10.1158/1078-0432.ccr-03-0166.

Bandiera S, Weidlich S, Harth V, Broede P, Ko Y, Friedberg T, et al. Proteasomal degradation of human CYP1B1: Effect of the Asn453Ser polymorphism on the post-translational regulation of CYP1B1 expression. Mol Pharmacol. 2005;67(2):435-43. doi: 10.1124/mol.104.006056.

Elfaki I, Mir R, Almutairi FM, Duhier FM. Cytochrome P450: Polymorphisms and roles in cancer, diabetes, and atherosclerosis. Asian Pac J Cancer Prev. 2018;19(8):2057-70. doi: 10.22034/APJCP.2018.19.8.2057.

Sowers MR, Wilson AL, Kardia SR, Chu J, McConnell DS. CYP1A1 and CYP1B1 polymorphisms and their association with estradiol and estrogen metabolites in women who are premenopausal and perimenopausal. Am J Med. 2006;119:S44-S51. doi: 10.1016/j. amjmed.2006.07.006.

McFadyen MC, Murray GI. Cytochrome P450 1B1: A novel anticancer therapeutic target. Future Oncol. 2005;1(2):259-63. doi: 10.1517/14796694.1.2.259.

Nishida CR, Everett S, Ortiz de Montellano PR. Specificity determinants of CYP1B1 estradiol hydroxylation. Mol Pharmacol. 2013;84(3):451-58. doi: 10.1124/mol.113.087700.

Li C, Long B, Qin X, Li W, Zhou Y. Cytochrome P1B1 (CYP1B1) polymorphisms and cancer risk: A meta-analysis of 52 studies. Toxicology. 2015;327:77-86. doi: 10.1016/j.tox.2014.11.007.

Ramadoss P, Marcus C, Perdew GH. Role of the aryl hydrocarbon receptor in drug metabolism. Expert Opin Drug Metab Toxicol. 2005;1(1):9-21. doi: 10.1517/17425255.1.1.9.

Rizzo R, Spaggiari F, Indelli M, Lelli G, Baricordi OR, Rimesi P, et al. Association of CYP1B1 with hypersensitivity induced by taxane therapy in breast cancer patients. Breast Cancer Res Treat. 2010;124(2):593-8. doi: 10.1007/s10549-010-1034-5.

González-Neira A. Pharmacogenetics of chemotherapy efficacy in breast cancer. Pharmacogenomics. 2012;13(6):677-90. doi: 10.2217/pgs.12.44.

Sissung TM, Danesi R, Price DK, Steinberg SM, de Wit R, Zahid M, et al. Association of the CYP1B1* 3 allele with survival in patients with prostate cancer receiving docetaxel. Mol Cancer Ther. 2008;7(1):19-26. doi: 10.1158/1535-7163.MCT-07-0557.

Bukowski K, Kciuk M, Kontek R. Mechanisms of multidrug resistance in cancer chemotherapy. Int J Mol Sci. 2020;21(9):3233. doi: 10.3390/ijms21093233.

Xie S, Tu Z, Xiong J, Kang G, Zhao L, Hu W, et al. CXCR4 promotes cisplatin-resistance of nonsmall cell lung cancer in a CYP1B1-dependent manner. Oncol Rep. 2017;37(2):921-28. doi: 10.3892/or.2016.5289.

Beaten J, Gelfond JA, Byrne JJ, Balic I, Crandall AC, Johnson Pais TL, et al. CYP1B1 variants are associated with prostate cancer in non-Hispanic and Hispanic Caucasians. Carcinogenesis. 2008;29(9):1751-57. doi: 10.1093/carcin/bgm300.

Ziv-Gal A, Gallicchio L, Miller SR, Zacur HA, Flaws JA. Genetic polymorphisms in the aryl hydrocarbon receptor signaling pathway as potential risk factors of menopausal hot flashes. Am J Obstet Gynecol. 2012;207(3):202.e9-202.e18. doi: 10.1016/j.ajog.2012.05.019.

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(6):1164-69. doi: 10.1093/carcin/bgn020.

Teng Y, He C, Zuo X, Li X. Catechol-Omethyltransferase and cytochrome P-450 1B1 polymorphisms and endometrial cancer risk: A meta-analysis. Int J Gynecol Cancer. 2013;23(3):422-30. doi: 10.1097/IGC.0b013e3182849e0d.

Bjerrum KB. Keratoconjunctivitis sicca and primary Sjögren’s syndrome in a Danish population aged 30–60 years. Acta Ophthalmol Scand. 1997;75(3):281-6. doi: 10.1111/j.1600-0420.1997.tb00774.x.

Harake D, Franco VI, Henkel JM, Miller TL, Lipshultz SE. Cardiotoxicity in childhood cancer survivors: strategies for prevention and management. Future Cardiol. 2012;8(4):647-70. doi: 10.2217/FCA.12.44.

Fleming I. The pharmacology of the cytochrome P450 epoxygenase/soluble epoxide hydrolase axis in the vasculature and cardiovascular disease. Pharmacol Rev. 2014;66(4):1106 40. doi: 10.1124/pr.113.007781.

Asnani A, Zheng B, Liu Y, Wang Y, Chen HH, Vohra A, et al. Highly potent visnagin derivatives inhibit Cyp1 and prevent doxorubicin cardiotoxicity. JCI Insight.2018;Jan11;3(1):e96753. doi:10.1172/jci.insight.96753.

Dutour R, Poirier D.Inhibitors of cytochrome P450 (CYP) 1B1. Eur J Med Chem.2017;135:296-06. doi:10.1016/j.ejmech.2017.04.042.