Abstract
Phase I enzymes, including cytochrome P450, family 1, subfamily A, and polypeptide 2 (CYP1A2), are involved in the activation of carcinogens to reactive intermediates that are capable of binding covalently to DNA to form DNA adducts, potentially initiating the carcinogenic process. The aim of present study was to investigate the association of CYP1A2 gene polymorphisms and haplotypes with lung cancer risk. A case-control study was carried out on 105 lung cancer patients and 189 controls. To investigate three CYP1A2 polymorphisms: rs2472299, rs2470890, rs11072508 we used a high resolution melting analysis. We found significant allele associations (rs2470890 and rs2422299) with lung cancer risk. We searched for meaningful associations for all variants in the dominant, recessive, and additive genetic models. Genotype associations in the recessive model were of marginal significance for the same single nucleotide polymorphisms. A haplotype analysis included five variants with the frequency higher than 1 %. The haplotype “acc”, present with the highest frequency, was associated with increased lung cancer risk (38.7 % vs. 31.5 %; OR 1.38; 95 %CI 0.95–2.01). On the contrary, rare haplotype “gtc” was significantly associated with decreased lung cancer risk in the Slovak population. In conclusion, the present study identified the risk alleles and haploid genotype associations of the CYP1A2 gene in lung cancer.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Aldrich MC, Selvin S, Hansen HM, Barcellos LF, Wrensch MR, Sison JD, Kelsey KT, Guffler PA, Quesenberry CHP, Seldin MF, Wiencke JK (2009) CYP1/2 haplotypes and lung cancer and assessment of confounding by population stratification. Cancer Res 69:2340–2348
Barret JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265
Bu ZB, Ye M, Cheng Y, Wu WZ (2014) Four polymorphisms in the cytochrome P450 1A2 (CYP1A2) gene and lung cancer risk: a meta-analysis. Asian Pac J Cancer Prev 15:5673–5679
Crespi CL, Penman BW, Steimel DT, Smith T, Yang CS, Sutter TR (1997) Development of a human lymphoblastoid cell line constitutively expressing human CYP1B1 cDNA: substrate specificity with model substrates an promutagens. Mutagenesis 12:83–89
Daly AK (2015) Polymorphic variants of cytochrome P450: relevance to cancer and other diseases. Adv Pharmacol 74:85–111
Guengerich FP, Shimada T (1998) Activation of procarcinogens by human cytochrome P450 enzymes. Mutat Res 400:201–213
Gunes A, Dahl ML (2008) Variation in CYP1A2 activity and its clinical implications: influence of environmental factors and genetic polymorphisms. Pharmacogenomics 9:625–637
He XF, Wei J, Liu ZZ, Xie JJ, Wang W, Du YP, Chen Y, Si HQ, Liu Q, Wu LX, Wei W (2014) Association between CYP1A2 and CYP1B1 polymorphisms and colorectal cancer risk: a meta-analysis. PLoS One 9, e100487. doi:10.1371/journal.pone.0100487
Klein K, Winter S, Tureinen M, Schwab M, Zanger UM (2010) Pathway-targeted pharmacogenomics of CYP1A2 in human liver. Front Pharmacol 1:1–20
Koressaar T, Remm M (2007) Enhancements and modifications of primer design program Primer3. Bioinformatics 23:1289–1291
Landi MT, Sinha R, Lang NP, Kadlubar FF (1999) Human cytochrome P4501A2. IARC Sci Publ 148:173–195
Ma Z, Guo W, Gong T, Niu HJ, Wang RW, Jiang YG (2014) CYP1A2 rs762551 polymorphism contributes to risk of lung cancer: a meta-analysis. Tumour Biol 35:2253–2257
Niwa T, Murayama N, Imagawa Y, Yamazaki H (2015) Regioselective hydroxylation of steroid hormones by human cytochromes P450. Drug Metab Rev 47:89–110
Özhan G, Mutur M, Ercan G, Alpertunga B (2014) Genetic variations in the xenobiotic-metabolizing enzymes CYP1A1, CYP1A2, CYP2C9, CYP2C19 and susceptibility to colorectal cancer among Turkish people. Genet Test Mol Biomarkers 18:223–228
Pavanello S, Mastrangelo G, Placidi D, Campagna M, Pulliero A, Carta A, Arici C, Porru S (2010) CYP1A2 polymorphisms, occupational and environmental exposures and risk of bladder cancer. Eur J Epidemiol 25:491–500
Rasmussen BB, Brix TH, Kyvik KO, Brosen K (2002) The interindividual differences in the 3-demethylation of caffeine alias CYP1A2 is determined by both genetic and environmental factors. Pharmacogenetics 12:473–478
Rendic S (2002) Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev 34:448–483
Rotunno M, Yu K, Lubin JH, Consonni D, Pesatori AC, Goldstein AM, Goldin LR, Wacholder S, Welch R, Burdette L, Chanock SJ, Bertazzi PA, Tucker MA, Caporaso NE, Chatterjee N, Bergen AW, Landi MT (2009) Phase I metabolic genes and risk of lung cancer: multiple polymorphisms and mRNA expression. PLoS One 4, e5652. doi:10.1371/journal.pone.0005652
Shao W, He J (2015) CYP1A2 rs2069514 polymorphism and lung cancer susceptibility: a meta-analysis. Annals of Translational Medicine 3:93–98
Shimizu T, Tateishi T, Hatano M, Fujii-Kuriyama Y (1991) Probing the role of lysines and arginines in the catalytic function of cytochrome P450d by site-directed mutagenesis. Interaction with NADPH-cytochrome P450 reductase. J Biol Chem 266:3372–3375
Skene DJ, Papagiannidou E, Hashemi E (2001) Contribution of CYP1A2 in the hepatic metabolism of melatonin: studies with isolated microsomal preparations and liver slices. J Pineal Res 31:333–342
The 1000 Genomes Project Consortium (2012) Nature 491:56–65
Untergasser A, Cutcutache I, Koressaar T, Ye J, Faircloth BC, Remm M, Rozen SG (2012) Primer3 – new capabilities and interfaces. Nucleic Acids Res 40(15), e115
Wang B, Zhou SF (2009) Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem 16:4066–4218
Xue H, Lu Y, Xue Z, Lin B, Chen J, Tang F, Huang G (2014) The effect of CYP1A1 and CYP1A2 polymorphisms on gastric cancer risk among different ethnicities: a systematic review and meta-analysis. Tumour Biol 35:4741–4756
Zhenzhen L, Xianghua L, Ning S, Zhan G, Chuanchuan R, Jie L (2013) Current evidence on the relationship between three polymorphisms in the CYP1A2 gene and the risk of cancer. Eur J Cancer Prev 22:607–619
Zhou SF, Liu JP, Chowbay B (2009a) Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug Metab Rev 41:89–295
Zhou SF, Yang LP, Zhou ZW, Liu YA, Chan E (2009b) Insights into the substrate specificity, inhibitors, regulation, and polymorphisms and the clinical impact of human cytochrome P450 1A2. AAPS Journal 11:481–494
Zhou SF, Wang B, Yang LP, Liu JP (2010) Structure, function, regulation and polymorphism and the clinical significance of human cytochrome P450 1A2. Drug Metab Rev 42:268–354
Acknowledgements
This work was supported by grants: the MZ SR 2012/25-UKMA-2, APVV-0412-11, and VEGA 1/0336/12.
Conflicts of Interest
The authors declare no conflicts of interest in relation to this article.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Matakova, T. et al. (2016). Associations of CYP1A2 Polymorphisms with the Risk Haplotypes in Lung Cancer in the Slovak Population. In: Pokorski, M. (eds) Advances in Respiratory Cancerogenesis. Advances in Experimental Medicine and Biology(), vol 911. Springer, Cham. https://doi.org/10.1007/5584_2016_220
Download citation
DOI: https://doi.org/10.1007/5584_2016_220
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-35097-4
Online ISBN: 978-3-319-35098-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)