Real-time PCR-analysis of the cytochrome P450 1B1 codon 432-polymorphism

Brüning, Thomas; Abel, Josef; Koch, Brigitte; Lorenzen, K.; Harth, Volker; Donat, Susanne; Sachinidis, Agapios; Vetter, Hans; Bolt, Hermann M.; Ko, Yon

doi:10.1007/s002040050631

Cited by 27 publications

(11 citation statements)

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“…The group with the highest serum cotinine levels (Cotinine ''high'') shows a Cyb1B1 expression, which is much higher than the Cyb1B1 expression level of the first and second third (Cotinine ''low'' and ''medium'') or of the non-smokers individuals. The allele frequencies for the studied population did not deviate from the Hardy-Weinberg equilibrium, and allele frequencies were similar to other published frequencies [9,[17][18][19].…”

Section: Discussionsupporting

confidence: 87%

Cyp1B1 mRNA expression in correlation to cotinine levels with respect to the Cyp1B1 L432V gene polymorphism

et al. 2010

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Cytochrome P450 1B1 (CYP1B1) is involved in the activation of a broad spectrum of procarcinogens. An association of the Cyp1B1 Leu432Val polymorphism with cancer as well as an impact on the enzyme activity has been described. To study gene-environmental interactions we investigated the quantitative Cyp1B1 mRNA expression in smokers (N = 102) and non-smokers (N = 192) with regards to the Cyp1B1 L432V gene polymorphism. Tobacco smoke exposure was assessed by serum cotinine levels. Genotypes were analysed by melting curve analysis and quantification of Cyp1B1 mRNA by real-time PCR. In comparing Cyp1B1 expression, significant differences between the two homozygote genotypes *1/*1 and *3/*3 (0.105 ± 0.019; n = 26 vs. 0.051 ± 0.017; n = 14; P = 0.039) and between the heterozygote genotype *1/*3 and *3/*3 (0.121 ± 0.029; n = 55 vs. 0.051 ± 0.017; n = 14; P = 0.039) of smokers were revealed. According to the serum cotinine levels, three subgroups (low; medium; high) were build. The group "high" (0.248 ± 0.089; n = 32) showed proportionally high Cyp1B1 mRNA expression compared to "medium" (0.101 ± 0.024; n = 33), "low" (0.086 ± 0.015; n = 32) and non-smokers (0.084 ± 0.007; n = 176). This result was reflected in the homozygote *1/*1 and the heterozygote *1/*3 genotypes. In contrast the homozygote *3/*3 genotype was missing the high Cyp1B1 mRNA expression in the cotinine subgroup "high". Our results suggest that genotypes carrying the C-allele (*1/*1 and *1/*3) at Cyp1B1 Leu432Val polymorphism show a higher response to environmental factors, such as tobacco smoke than homozygote *3/*3 genotypes.

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Section: Discussionsupporting

confidence: 87%

Cyp1B1 mRNA expression in correlation to cotinine levels with respect to the Cyp1B1 L432V gene polymorphism

et al. 2010

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“…The PCR products were hybridised with the following probes: 5 0 -AAA AAA GAC GCA GGA TT-3 0 and 5 0 -AAA AAA GAT GCA GGA TT-3 0 . The CYP1B1 was genotyped for 241 cases and 290 controls recruited from 1995 to 1999 by a real-time PCR-based method as described by Brüning et al (1999).…”

Section: Genotypingmentioning

confidence: 99%

Genetic polymorphisms of cytochrome P450 19 and 1B1, alcohol use, and breast cancer risk in Korean women

Lee

Abel

et al. 2003

Br J Cancer

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A case -control study was performed to assess the potential influence of CYP19 Arg 264 Cys and CYP1B1 Leu 432 Val polymorphisms on breast cancer risk in a series of Korean breast cancer patients and controls. The results suggest that the CYP19 Arg 264 Cys polymorphism modifies breast cancer risk (OR ¼ 1.5, 95% CI ¼ 1.1 -2.2), especially in association with alcohol consumption (P for interaction ¼ 0.04), whereas the CYP1B1 Leu 432 Val polymorphism appears to play no role here. Breast cancer is the second most frequent cancer in Korean women and its incidence is increasing (Yoo et al, 1998). Lifetime cumulative exposure to oestrogens is known as the most important risk factor for breast cancer (Yager, 2000). A variety of different enzymes are involved in the synthesis of oestrogen from cholesterol and further metabolism of oestrogen (Thompsen and Ambrosone, 2000). Polymorphisms of genes encoding for these proteins are regarded as the candidates for elevated breast cancer risk.The CYP19 gene encodes aromatase, which catalyses the formation of oestrogens from testosterone and androstenedione. To date, several polymorphisms have been found in the CYP19 gene (i.e. Polymeropulous et al, 1991;Sourdaine et al, 1994;Siegelmann-Danieli and Buetow, 1999;Healey et al, 2000;Miyoshi et al, 2000). One of these, a C-to-T variation in exon 7 resulting in an Arg 264 Cys amino-acid exchange, has been shown to be very common in Asians (Watanabe et al, 1997;Miyoshi et al, 2000) and could thus be an important modifier of breast cancer risk in this ethnic group.The CYP1B1 enzyme is known to be involved in the formation of 4-hydroxyoestradiol, which is a catechol metabolite of oestrogen (Hayes et al, 1996). A C-to-G variation in exon 3 of the CYP1B1 gene results in a Leu 432 Val amino-acid exchange. The Leu/Leu genotype has been associated with increased breast cancer risk in an Asian population (Zheng et al, 2000) but controversial results have been reported as well (Bailey et al, 1998;Watanabe et al, 2000).In this study, we have evaluated the potential influence of CYP19 Arg 264 Cys and CYP1B1 Leu 432 Val polymorphisms on the breast cancer risk among Korean women as an extension of our previous work in this study population (Park et al, 2000;Yim et al, 2001). MATERIALS AND METHODS Study subjectsThe criteria of subject selection and details of data collection on lifestyle have been described elsewhere (Park et al, 2000;Yim et al, 2001). Eligible study population consisted of 389 incident breast cancer cases and 346 controls with no other known cancer or systemic disease, admitted in 1995 -2001 to three teaching hospitals located in Seoul, Korea (Seoul National University Hospital, Borame Hospital, and Asan Medical Center). Each patient was frequency-matched to one control in the following age groups : under 30, 30 -34, 35 -39, 40 -44, 45 -49, 50 -54, 55 -59, 60 -69, and over 70 years; 288 cases and 288 controls were selected and genotyped for CYP19. Informed consents were obtained at the time of blood withdrawal. Information on demogr...

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“…genomic dna was isolated from whole blood using the Qiaamp Blood Mini kit (Qiagen, Hilden, germany). real-time Pcr analysis and melting-curve analysis of the cytochrome P-4501A1 A4889G and T6235C polymorphisms were performed as previously described by Harth et al (13), and of the cytochrome P-4501B1 codon 432 polymorphism as previously described by Brüning et al (14). Both the PCR primers and the fluorescentlabelled detection probes were commercially synthesized by Tib Molbiol (Berlin, germany).…”

Section: Methodsmentioning

confidence: 99%

CYP1A1 and CYP1B1 polymorphisms as modifying factors in patients with pneumoconiosis and occupationally related tumours: A pilot study

Schneider

Bernges²

2009

Mol Med Rep

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Abstract. CYP1A1 and CYP1B1 are involved in the metabolism of carcinogens. The effect of CYP1A1 and CYP1B1 polymorphisms as genetic modifiers of risk was investigated in individuals with asbestos, silica dust or ionizing radiationinduced occupational tumours compared to exposed non-cancer subjects suffering from pneumoconiosis, particularly in relation to tobacco smoking. CYP1A1 T6235C, CYP1A1 A4889G and CYP1B1 codon 432 polymorphisms were determined by realtime Pcr analysis in patients with asbestos-related lung cancer (n=39), patients with diffuse malignant mesotheliomas (n=19), lung cancer in silicosis patients (n=7), uranium miners with lung cancer (uMlc) (n=40), patients with asbestosis (n=181), and silicosis patients (n=204). The results were compared to those from a healthy unexposed control group (n=50) not exposed to carcinogenic (or fibrogenic) agents in the workplace. an additional healthy control group (n=134) comprised smokers and ex-smokers. allele frequencies were within the range described for caucasians. Multivariate analysis revealed that patients with occupational diseases with the susceptible CYP1A1 T6235C genotype had a calculated risk ranging from or=0.5 (95% ci 0.18-1.36) for uMlc to or=1.23 (95% ci 0.39-4.05) for uranium miners with silicosis. The risk for patients with the susceptible CYP1A1 A4889G allele was calculated as being between or=0.39 (95% ci 0.10-1.54) for mesothelioma patients and or=1.54 (95% ci 0.49-4.89) for uMlc. CYP1B1 Val432Leu polymorphisms were associated with a risk of or=0.56 (95% ci 0.2-1.55) for uMlc and or=1.52 (95% ci 0.68-3.39) for asbestos-exposed lung cancer patients. By analyzing the interaction between tobacco smoking, type of exposure to carcinogens and the genotypes, it was determined that smoking and the presence of the susceptible genotypes did not have a combined effect. in this pilot study, the analyzed polymorphism had no consistent modifying effect on pneumoconiosis or occupationally related tumours. Introductionindividual differences in susceptibility to occupationally induced carcinomas are in part ascribed to genetic differences in metabolic activity regarding the activation or detoxification of environmental carcinogens. Human lung cancer is caused by exposure to carcinogens such as polycyclic aromatic hydrocarbons (PaH), found mainly in cigarette smoke, but can also be caused by exposure to carcinogens in the workplace, such as asbestos, ionizing radiation or silica dust.Most environmental carcinogens require metabolic activation by Phase i enzymes, cytochrome P-450s, to their reactive electrophilic intermediates. Several forms of P-450 have been identified. CYP1A1 is involved in the bioactivation of carcinogenic PaH. in a caucasian population, an association was found between CYP1A1 homozygous Mspi rFlP and lung cancer (1,2).In vitro studies have demonstrated that asbestos fibres exert a destructive effect through the generation of reactive oxygen species (roS), which leads to alterations in mitochondrial function and the activation of several...

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Real-time PCR-analysis of the cytochrome P450 1B1 codon 432-polymorphism

Cited by 27 publications

References 0 publications

Cyp1B1 mRNA expression in correlation to cotinine levels with respect to the Cyp1B1 L432V gene polymorphism

Cyp1B1 mRNA expression in correlation to cotinine levels with respect to the Cyp1B1 L432V gene polymorphism

Genetic polymorphisms of cytochrome P450 19 and 1B1, alcohol use, and breast cancer risk in Korean women

CYP1A1 and CYP1B1 polymorphisms as modifying factors in patients with pneumoconiosis and occupationally related tumours: A pilot study

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