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Archives of Industrial Hygiene and Toxicology

The Journal of Institute for Medical Research and Occupational Health

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Volume 60, Issue 2


Genetic Polymorphism of Metabolic Enzymes P450 (CYP) as a Susceptibility Factor for Drug Response, Toxicity, and Cancer Risk

Nada Božina
  • Clinical Institute of Laboratory Diagnosis, Zagreb University School of Medicine and University Hospital Centre Zagreb, Zagreb, Croatia
  • Department of Pharmacology, Zagreb University School of Medicine, Zagreb, Croatia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Vlasta Bradamante / Mila Lovrić
  • Clinical Institute of Laboratory Diagnosis, Zagreb University School of Medicine and University Hospital Centre Zagreb, Zagreb, Croatia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2009-07-06 | DOI: https://doi.org/10.2478/10004-1254-60-2009-1885

Genetic Polymorphism of Metabolic Enzymes P450 (CYP) as a Susceptibility Factor for Drug Response, Toxicity, and Cancer Risk

The polymorphic P450 (CYP) enzyme superfamily is the most important system involved in the biotransformation of many endogenous and exogenous substances including drugs, toxins, and carcinogens. Genotyping for CYP polymorphisms provides important genetic information that help to understand the effects of xenobiotics on human body. For drug metabolism, the most important polymorphisms are those of the genes coding for CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5, which can result in therapeutic failure or severe adverse reactions. Genes coding for CYP1A1, CYP1A2, CYP1B1, and CYP2E1 are among the most responsible for the biotransformation of chemicals, especially for the metabolic activation of pre-carcinogens. There is evidence of association between gene polymorphism and cancer susceptibility. Pathways of carcinogen metabolism are complex, and are mediated by activities of multiple genes, while single genes have a limited impact on cancer risk. Multigenic approach in addition to environmental determinants in large sample studies is crucial for a reliable evaluation of any moderate gene effect. This article brings a review of current knowledge on the relations between the polymorphisms of some CYPs and drug activity/toxicity and cancer risk.

Uloga genskog polimorfizma metaboličkih enzima P450(CYP) kao čimbenika osjetljivosti na učinkovitost i toksičnost lijeka te nastanak karcinoma

Keywords: cancer risk; cytochrome P450; drug metabolism; genotyping; pharmacogenomics; polymorphic allele; xenobiotics

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About the article

Published Online: 2009-07-06

Published in Print: 2009-06-01

Citation Information: Archives of Industrial Hygiene and Toxicology, Volume 60, Issue 2, Pages 217–242, ISSN (Print) 0004-1254, DOI: https://doi.org/10.2478/10004-1254-60-2009-1885.

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Disease Markers, 2018, Volume 2018, Page 1
Oncology Letters, 2014, Volume 8, Number 6, Page 2407
Xiao-Yang Zhou, Xiao-Xia Hu, Meng-Fang Li, Hao Wang, Li-Qun Zhang, Guo-Xin Hu, and Jian-Ping Cai
Drug Testing and Analysis, 2017
Mariusz Panczyk
World Journal of Gastroenterology, 2014, Volume 20, Number 29, Page 9775
Anca Oana Docea, Loukia Vassilopoulou, Domniki Fragou, Andreea Letitia Arsene, Concettina Fenga, Leda Kovatsi, Dimitrios Petrakis, Valerii N. Rakitskii, Alexander E. Nosyrev, Boris N. Izotov, Kirill S. Golokhvast, Alexander M. Zakharenko, Antonis Vakis, Christina Tsitsimpikou, and Nikolaos Drakoulis
Toxicology Reports, 2017, Volume 4, Page 335
Thaís de Almeida Pedrete, Caroline de Lima Mota, Eline Simões Gonçalves, and Josino Costa Moreira
Cadernos Saúde Coletiva, 2016, Volume 24, Number 2, Page 262
Driss Afilal, Mohamed Amine Basselam, Zahra Brakez, Said Chouham, António Brehm, and El Hassan Izaabel
Genetic Testing and Molecular Biomarkers, 2017, Volume 21, Number 5, Page 298
Chaitali Ghosh, Mohammed Hossain, Jesal Solanki, Imad M. Najm, Nicola Marchi, and Damir Janigro
Epilepsia, 2017, Volume 58, Number 4, Page 576
Kanika Verma, Kaavya Kannan, Shanthi V, Sethumadhavan R, Karthick V, and Ramanathan K
Phytochemical Analysis, 2017, Volume 28, Number 3, Page 230
Aggeliki Daraki, Katerina Kakosaiou, Sophia Zachaki, Constantina Sambani, Vassiliki Aleporou-Marinou, Panagoula Kollia, and Kalliopi N. Manola
Cancer Genetics, 2016, Volume 209, Number 11, Page 525
Wafaa Moustafa M. Abo El Fotoh, Sameh abd Allah Abd el naby, Mona Salah El-din Habib, Abeer Ahmed ALrefai, and Zeinab A. Kasemy
Seizure, 2016, Volume 41, Page 75
Mandana Ghisari, Hans Eiberg, Manhai Long, and Eva C Bonefeld-Jørgensen
Environmental Health, 2014, Volume 13, Number 1
Mirza Bojić, Željko Debeljak, Maja Tomičić, Marica Medić-Šarić, and Siniša Tomić
Nutrition Journal, 2011, Volume 10, Number 1
Yurie Watanabe, Shuichi Fukuyoshi, Masahiro Hiratsuka, Noriyuki Yamaotsu, Shuichi Hirono, Ohgi Takahashi, and Akifumi Oda
Journal of Molecular Graphics and Modelling, 2016, Volume 68, Page 48
Valon Krasniqi, Aleksandar Dimovski, Iva Klarica Domjanović, Ivan Bilić, and Nada Božina
Archives of Industrial Hygiene and Toxicology, 2016, Volume 67, Number 1, Page 1
Hailin Wang, Lianqiang Hui, Chun Li, Ting Liu, Chang’an Yu, Chunyu Cao, Ran Hao, and Yi Zhang
Health, 2016, Volume 08, Number 04, Page 370
George N. Goulielmos, Maria I. Zervou, Effie Myrthianou, Agata Burska, Timothy B. Niewold, and Frederique Ponchel
Gene, 2016, Volume 583, Number 2, Page 90
Deolinda Pereira, Joana Assis, Mónica Gomes, Augusto Nogueira, and Rui Medeiros
European Journal of Clinical Pharmacology, 2016, Volume 72, Number 5, Page 545
G. Pahlke, C. Tiessen, K. Domnanich, N. Kahle, I.A.M. Groh, I. Schreck, C. Weiss, and D. Marko
Toxicology Letters, 2016, Volume 240, Number 1, Page 93
Robert J. Foxenberg, Corie A. Ellison, James B. Knaak, Changxing Ma, and James R. Olson
Toxicology, 2011, Volume 285, Number 1-2, Page 57
L. Z. Akhmadishina, G. F. Korytina, O. V. Kochetova, and T. V. Viktorova
Russian Journal of Genetics: Applied Research, 2015, Volume 5, Number 5, Page 507
S. Helmig and J. Schneider
Zentralblatt für Arbeitsmedizin, Arbeitsschutz und Ergonomie, 2015, Volume 65, Number 6, Page 347
Antonio Gómez-Martín, Antonio F. Hernández, Luis Javier Martínez-González, Beatriz González-Alzaga, Miguel Rodríguez-Barranco, Inmaculada López-Flores, Clemente Aguilar-Garduno, and Marina Lacasana
Chemosphere, 2015, Volume 139, Page 534
Romilly E. Hodges and Deanna M. Minich
Journal of Nutrition and Metabolism, 2015, Volume 2015, Page 1
Elena De Mattia, Erika Cecchin, and Giuseppe Toffoli
Drug Resistance Updates, 2015, Volume 20, Page 39
Juan Gong, Yuan Jiang, Ningbo Hao, Bo Zhu, and Yongsheng Li
Scientific Reports, 2015, Volume 5, Number 1
Randa G. Naffa, Abdalla S. Awidi, Al-Motassem F. Yousef, and Said I. Ismail
Cancer Epidemiology, 2012, Volume 36, Number 1, Page 68
Miriam Hernando-Rodriguez, Natalia Rey-Barja, Xabier Marichalar-Mendia, Maria J. Rodriguez-Tojo, Amelia Acha-Sagredo, and Jose M. Aguirre-Urizar
Journal of Oral Pathology & Medicine, 2012, Volume 41, Number 1, Page 1
Nathália Moreno Cury, Anelise Russo, Ana Lívia Silva Galbiatti, Mariângela Torreglosa Ruiz, Luiz Sérgio Raposo, José Victor Maniglia, Érika Cristina Pavarino, and Eny Maria Goloni-Bertollo
Molecular Biology Reports, 2012, Volume 39, Number 2, Page 1055
Christoph Dorn, Frauke Bataille, Erwin Gaebele, Jörg Heilmann, and Claus Hellerbrand
Food and Chemical Toxicology, 2010, Volume 48, Number 7, Page 1890
Adam S. Duerfeldt and Brian S.J. Blagg
Bioorganic & Medicinal Chemistry Letters, 2010, Volume 20, Number 17, Page 4983
Michael E. Grossmann, Amitabha Ray, Katai J. Nkhata, Dmitry A. Malakhov, Olga P. Rogozina, Soner Dogan, and Margot P. Cleary
Cancer and Metastasis Reviews, 2010, Volume 29, Number 4, Page 641
Prachi Bajpai, Anil Kumar Tripathi, and Deepa Agrawal
Molecular and Cellular Biochemistry, 2010, Volume 336, Number 1-2, Page 49
Ye-Ji Lim, Eun-Young Cha, Hye-Eun Jung, Jong-Lyul Ghim, Su-Jun Lee, Eun-Young Kim, and Jae-Gook Shin
Translational and Clinical Pharmacology, 2014, Volume 22, Number 2, Page 70
P. Mota, H. C. Silva, M. J. Soares, A. Pego, M. Loureiro, C. Robalo Cordeiro, and F. J. Regateiro
Journal of Cancer Research and Clinical Oncology, 2015, Volume 141, Number 5, Page 851
Ryeo-Eun Go, Kyung-A Hwang, and Kyung-Chul Choi
The Journal of Steroid Biochemistry and Molecular Biology, 2015, Volume 147, Page 24
Hsiu-Chin Lu, Ya-Sian Chang, Chun-Chi Chang, Ching-Hsiung Lin, and Jan-Gowth Chang
Journal of Clinical Laboratory Analysis, 2015, Volume 29, Number 3, Page 220
Corie A. Ellison, Soheir S. Abou El-Ella, Maha Tawfik, Pamela J. Lein, and James R. Olson
Journal of Toxicology and Environmental Health, Part A, 2012, Volume 75, Number 4, Page 232
Shih-Chi Su, Wen-Hung Chung, and Shuen-Iu Hung
BioMed Research International, 2014, Volume 2014, Page 1
Sabha Rasool, Vamiq Rasool, Tahira Naqvi, Bashir A. Ganai, and Bhahwal Ali Shah
Tumor Biology, 2014, Volume 35, Number 6, Page 5067
Mateusz Kurzawski, Violetta Dziedziejko, Mariola Post, Maciej Wójcicki, Elżbieta Urasińska, Janusz Miętkiewski, and Marek Droździk
Pharmacological Reports, 2012, Volume 64, Number 4, Page 927
Gül Özhan, Mine Mutur, Gulcin Ercan, and Buket Alpertunga
Genetic Testing and Molecular Biomarkers, 2014, Volume 18, Number 4, Page 223
Vivien How, Zailina Hashim, Patimah Ismail, Salmiah Md Said, Dzolkhifli Omar, and Shamsul Bahri Mohd Tamrin
Journal of Agromedicine, 2014, Volume 19, Number 1, Page 35
Zheng Ma, Wei Guo, Taiqian Gong, Hui-Jun Niu, Ru-Wen Wang, and Yao-Guang Jiang
Tumor Biology, 2014, Volume 35, Number 3, Page 2253
Yu Lu, Qiliu Peng, Zhiyu Zeng, Jian Wang, Yan Deng, Li Xie, Cuiju Mo, Jie Zeng, Xue Qin, and Shan Li
Journal of the Neurological Sciences, 2014, Volume 336, Number 1-2, Page 161
Saraswathy Seema, Manu Krishnan, Arun K. Harith, Kavita Sahai, Satish R. Iyer, Vimal Arora, and Rajendra P. Tripathi
Journal of Oral Pathology & Medicine, 2014, Volume 43, Number 7, Page 471
A.A.S. Reis, D.M. Silva, M.P. Curado, and A.D. da Cruz
Genetics and Molecular Research, 2010, Volume 9, Number 4, Page 2222
Zhong Tian, Yi-Ling Li, Lin Zhao, and Chen-Liang Zhang
Gene, 2013, Volume 524, Number 2, Page 168
Ariane Wohlfarth, Jana Naue, Sabine Lutz-Bonengel, Sebastian Dresen, and Volker Auwärter
The Journal of Clinical Pharmacology, 2012, Volume 52, Number 8, Page 1200
Monica Sankhwar and S.N. Sankhwar
Urologic Oncology: Seminars and Original Investigations, 2014, Volume 32, Number 1, Page 28.e33
Santosh Kumar
Expert Opinion on Drug Metabolism & Toxicology, 2010, Volume 6, Number 2, Page 115
Giovanna Gentile, Marina Borro, Maurizio Simmaco, Serena Missori, Noemi Lala, and Paolo Martelletti
Expert Opinion on Drug Metabolism & Toxicology, 2011, Volume 7, Number 1, Page 39
Li-Ping Zhou, Fan Yao, Hong Luan, Yin-Ling Wang, Xi-Hua Dong, Wen-Wen Zhou, and Qi-Hui Wang
Tumor Biology, 2013, Volume 34, Number 2, Page 649
Shashi Amur, Issam Zineh, Darrell R Abernethy, Shiew-Mei Huang, and Lawrence J Lesko
Personalized Medicine, 2010, Volume 7, Number 6, Page 633
Ghada Salameh, Kamal Al. Hadidi, and Mohammad El. Khateeb
Environmental Toxicology and Pharmacology, 2012, Volume 34, Number 1, Page 23
Ami Oguro, Koichi Sakamoto, Yoshihiko Funae, and Susumu Imaoka
Drug Metabolism and Pharmacokinetics, 2011, Volume 26, Number 4, Page 407

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