Abstract
Cytochrome P450 1B1 (CYP1B1) is a key P450 enzyme, which could catalyze the formation of 4-hydroxy estrogen metabolites and play a role in estrogen-dependent cancers. We hypothesized that genetic variant in CYP1B1 may modify individual susceptibility to cervical cancer. The aim of this study was to evaluate the association between CYP1B1 C4326G polymorphism and cervical cancer risk in Chinese women. We extracted the peripheral blood samples in 250 patients with cervical cancer and 250 female controls. The matrix-assisted laser desorption ionization time-of-flight mass spectrometry method and direct DNA sequencing were performed to detect the polymorphism. The frequencies of CC, CG, and GG genotypes of CYP1B1 C4326G in cases and controls were 66.0, 26.8, 7.2 % and 75.2, 21.6, and 3.2 %, respectively, and there was a significant difference between the two groups (P = 0.034). Compared with the wild-type CC genotype, the variant GG genotype was associated with a significantly increased risk of cervical cancer (adjusted OR = 2.30; 95 % CI = 1.02, 5.50). Moreover, stratification analysis by age, smoking, drinking, human papillomaviruses (HPV) 16 or 18 carrier status, and family history of cervical cancer, we found that the variant genotypes containing the G allele were associated with a significantly increased risk of cervical cancer among HPV 16 or 18-positive individuals (adjusted OR = 2.85; 95 % CI = 1.45, 5.62) and among women younger than 45 years old (adjusted OR = 1.87; 95 % CI = 1.03, 3.37). These results suggest that CYP1B1 C4326G polymorphism may increase risk of cervical cancer in Chinese women, especially among young individuals with high-risk HPV infection.
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Abbreviations
- CYP1B1:
-
Cytochrome P450 1B1
- OR:
-
Odds ratio
- CI:
-
Confidence interval
- PCR:
-
Polymerase chain reaction
- SNP:
-
Single nucleotide polymorphisms
- HWE:
-
Hardy–Weinberg equilibrium
References
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.
Schoell WMJ, Janicek MF, Mirhashemi R. Epidemiology and biology of cervical cancer. Semin Surg Oncol. 1999;16:203–11.
Berumen-Campos J. Human papillomavirus and cervical cancer. Gac Med Mex. 2006;142:51–9.
Franceschi S. The IARC commitment to cancer prevention: the example of papillomavirus and cervical cancer. Recent Results Cancer Res. 2005;166:277–97.
Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189:12–9.
Paracchini V, Raimondi S, Gram IT, et al. Meta- and pooled analyses of the cytochrome P-450 1B1 Val432Leu polymorphism and breast cancer: a HuGE-GSEC review. Am J Epidemiol. 2007;165:115–25.
Hayes CL, Spink DC, Spink BC, et al. Seventeen beta-estradiol hydroxylation catalyzed by human cytochrome P450 1B1. Proc Natl Acad Sci USA. 1996;93:9776–81.
Shah PP, Singh AP, Singh M, et al. Association of functionally important polymorphisms in cytochrome P4501B1 with lung cancer. Mutat Res. 2008;643:4–10.
Sasaki M, Kaneuchi M, Fujimoto S, Tanaka Y, Dahiya R. CYP1B1 gene in endometrial cancer. Mol Cell Endocrinol. 2003;202:171–6.
Meyer UA, Gut J, Kronbach T, et al. The molecular mechanisms of two common polymorphisms of drug oxidation evidence for functional changes in cytochrome P-450 isozymes catalyzing bufuralol and mephenytoin oxidation. Xenobiotica. 1986;16:449–64.
Tang YM, Wo Y-YP, Stewart J, et al. Isolation and characterization of the human cytochrome P450 CYP1B1 gene. J Biol Chem. 1996;271:28324–30.
Stoilov I, Akarsu AN, Sarfarazi M. Identification of three different truncating mutations in cytochrome P4501B1 (CYP1B1) as the principal cause of primary congenital glaucoma (buphthalmos) in families linked to the GLC3A locus on chromosome 2p21. Hum Mol Genet. 1997;6:641–7.
Stoilov I, Akarsu AN, Alozie I, et al. Sequence analysis and homology modeling suggest that primary congenital glaucoma on 2p21 results from mutations disrupting either the hinge region or the conserved core structures of cytochrome P4501B1. Am J Hum Genet. 1998;62:573–84.
Roos PH, Bolt HM. Cytochrome P450 interactions in human cancers: new aspects considering CYP1B1. Expert Opin Drug Metab Toxicol. 2005;1:187–202.
Hanna IH, Dawling S, Roodi N, Guengerich FP, Parl FF. Cytochrome P450 1B1 (CYP1B1) pharmacogenetics: association of polymorphisms with functional differences in estrogen hydroxylation activity. Cancer Res. 2000;60:3440–4.
Shimada T, Watanabe J, Kawajiri K, et al. Catalytic properties of polymorphic human cytochrome P450 1B1 variants. Carcinogenesis. 1999;20:1607–13.
Li DN, Seidel A, Pritchard MP, et al. Polymorphisms in P450 CYP1B1 affect the conversion of estradiol to the potentially carcinogenic metabolite 4-hydroxyestradiol. Pharmacogenetics. 2000;10:343–53.
Xie Y, Liu GQ, Miao XY, et al. CYP1B1 Leu432Val polymorphism and colorectal cancer risk among Caucasians: a meta-analysis. Tumor Biol. 2012;33(3):809–16.
Wang F, Zou YF, Sun GP, Su H, Huang F. Association of CYP1B1 gene polymorphisms with susceptibility to endometrial cancer: a meta-analysis. Eur J Cancer Prev. 2011;20:112–20.
Chen B, Qiu LX, Li Y, et al. The CYP1B1 Leu432Val polymorphism contributes to lung cancer risk: evidence from 6,501 subjects. Lung Cancer. 2010;70:247–52.
Shimada T, Oda Y, Gillam EM, et al. Metabolic activation of polycyclic aromatic hydrocarbons and other procarcinogens by cytochromes P450 1A1 and P450 1B1 allelic variants and other human cytochromes P450 in Salmonella typhimurium NM2009. Drug Metab Dispos. 2001;29:1176–82.
Kim JH, Stansbury KH, Walker NJ, et al. Metabolism of benzo[a]pyrene and benzo[a]pyrene-7, 8-diol by human cytochrome P450 1B1. Carcinogenesis. 1998;19:1847–53.
Ko Y, Abel J, Harth V, et al. Association of CYP1B1 codon 432 mutant allele in head and neck squamous cell cancer is reflected by somatic mutations of p53 in tumor tissue. Cancer Res. 2001;61:4398–404.
Lemm F, Wilhelm M, Roos PH. Occupational exposure to polycyclic aromatic hydrocarbons suppresses constitutive expression of CYP1B1 on the transcript level in human leukocytes. Int J Hyg Environ Health. 2004;207:325–35.
Xu W, Zhou Y, Hang X, Shen D. Current evidence on the relationship between CYP1B1 polymorphisms and lung cancer risk: a meta-analysis. Mol Biol Rep. 2012;39:2821–9.
Cui L, Dillehay K, Chen W, Shen D, Dong Z, Li W. Association of the CYP1B1 Leu432Val polymorphism with the risk of prostate cancer: a meta-analysis. Mol Biol Rep. 2012;39:7465–71.
Bosch FX, Lorincz A, Munoz N, et al. The causal relation between human papillomavirus and cervical cancer. J Clin Pathol. 2002;55:244–65.
Castellsague X, Boscho FX, Munoz N. Environmental cofactors in HPV carcinogenesis. Virus Res. 2002;89:191–9.
Winkelstein Jr W. Smoking and cancer of the uterine cervix: hypothesis. Am J Epidemiol. 1977;106:257–9.
Plummer M, Herrero R, Franceschi S, et al. IARC multicenter cervical cancer study group. Smoking and cervical cancer: pooled analysis of the IARC multi-centric case–control study. Cancer Causes Contorl. 2003;9:805–14.
Wenzlaff AS, Cote ML, Bock CH, et al. CYP1A1 and CYP1B1 polymorphisms and risk of lung cancer among never smokers: a population-based study. Carcinogenesis. 2005;26:2207–12.
Sørensen M, Autrup H, Tjønneland A, Overvad K, Raaschou-Nielsen O. Genetic polymorphisms in CYP1B1, GSTA1, NQO1, and NAT2 and the risk of lung cancer. Cancer Lett. 2005;221:185–90.
Yoon KA, Kim JH, Gil HJ, et al. CYP1B1, CYP1A1, MPO, and GSTP1 polymorphisms and lung cancer risk in never-smoking Korean women. Lung Cancer. 2008;60:40–6.
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Li, Y., Tan, SQ., Ma, QH. et al. CYP1B1 C4326G polymorphism and susceptibility to cervical cancer in Chinese Han women. Tumor Biol. 34, 3561–3567 (2013). https://doi.org/10.1007/s13277-013-0935-4
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DOI: https://doi.org/10.1007/s13277-013-0935-4