The Relationship of ABCB1/MDR1 and CYP1A1 Variants with the Risk of Disease Development and Shortening of Overall Survival in Patients with Multiple Myeloma

(1) Background: The aim of our study was to analyze the possible relationship of ABCB1 and CYP1A1 gene variants with susceptibility and outcome of multiple myeloma (MM); (2) Methods: Genomic DNA samples from 110 newly-diagnosed MM patients and 100 healthy blood donors were analyzed by methods-PCR-RFLP (for ABCB1 3435C > T, CYP1A1 6235T > C—m1), automated DNA sequencing (for ABCB1 1236C > T, 2677G > T/A) and allele-specific PCR (for CYP1A1 4889A > G—m2); (3) Results: The genotypic frequencies of CYP1A1 4889A > G variant were not in Hardy-Weinberg equilibrium for MM patients. The presence of m1 and m2 CYP1A1 alleles decreased the risk of MM—OR = 0.49 (p = 0.011) and OR = 0.27 (p = 0.0003), respectively. In turn, TT genotype (ABCB1 2677G > T/A) increased the risk of this disease (p = 0.007). In the multivariate Cox analysis CT + TT genotypes (ABCB1 3435C > T) were associated with decreased risk of death (HR = 0.29, p = 0.04). In log-rank test in patients with CT genotype (ABCB1 3435C > T) was observed association of overall survival with the type of treatment; (4) Conclusions: Our findings suggest that T-alleles of ABCB1 2677G > T/A and m1/m2 alleles of CYP1A1 affected the susceptibility of MM. Moreover, T-allele of ABCB1 3435C > T might be independent positive prognostic factor in MM.

Polymorphism of the cytochrome P450 CYP1A1 (Ile462Val) gene in the populations of Balkars and Karachays

BACKGRAUND: Cytochrome P450 is an enzyme involved in the metabolism of phase I xenobiotics, toxins, endogenous hormones and pharmaceuticals. AIM: Is studying the polymorphism of the CYP1A1 gene (Ile462Val, rs1048943) in the Turkic-speaking populations of the central part of the North Caucasus Region (Balkars and Karachays). MATERIALS AND METHODS: We analyzed DNA isolated from leukocytes of peripheral venous blood of a total of 177 unrelated Balkars and Karachays (104 Balkars, 73 Karachays). RESULTS: The ethnicity of the studied individuals was established, indicating their ancestors up to the third generation. The method of genotyping was performed by real-time PCR using competing TaqMan probes. As a result: the frequency of the 462Val variant in the sample of Balkars was 8,6% (95% CI 5,2113,33), slightly above the frequency range found in European populations. In the sample of Karachays, the frequency of the 462Val allele was 7,5% (95% CI 9,8213.08), which is the upper limit of values typical for European populations. CONCLUSION: In the Turkic-speaking populations of the central part of the North Caucasus, the CYP1A1 462Val allele occurs with a frequency characteristic of the Near Eastern and European populations.

Association between CYP1A1 Gene Polymorphisms and Cervical Cancer Susceptibility: A Meta-Analysis

IntroductionThis study is to systemically analyze the association of CYP1A1 gene MspI and Ile462Val polymorphisms with cervical cancer susceptibility.Material and methodsThe literatures about the associations between CYP1A1 polymorphism and cervical cancer were retrieved through PubMed, Embase, Chinese biomedical literature database, Wanfang database, Database of Chinese Scientific and Technical Periodicals (VIP) and China Knowledge Network. Hardy-Weinberg equilibrium test was used to evaluate the quality of the included studies, and the data in the studies selected were analyzed by Stata 12.0 software. Potential publication bias was assessed with funnel plots and a modified Egger’s linear regression test.ResultsA total of 17 studies were enrolled in this analysis. There were 14 articles on MspI locus polymorphism, including 2448 cases and 2520 controls. We found significant association between MspI locus polymorphism and cervical cancer susceptibility (C vs. T, OR 1.333, 95% CI 1.214-1.464, P≤0.001; CC vs. TT, OR 1.962, 95% CI 1.571-2.450, P≤0.001; CC/CT vs.TT, OR1.591, 95% CI1.406-1.800, P≤0.001; CCvs.TT/CT,OR1.429, 95% CI 1.177-1.736, P≤0.001). Totally, 11 articles, including 2137 cases and 2116 controls, analyzed the Ile462Val locus polymorphism and the risk of cervical cancer. The result showed significant association between Ile462Val locus polymorphism and cervical cancer susceptibility (Val vs. Ile, OR 1.338, 95% CI 1.199-1.493, P≤0.001; ValVal vs. IleIle, OR 1.576, 95% CI 1.188-2.090, P=0.002; ValVal/ValIle vs. IleIle, OR 1.498; 95% CI 1.299-1.728, P≤0.001).ConclusionsBoth MspI and Ile462Val polymorphisms of CYP1A1 gene are associated with the risk of cervical cancer.

Polymorphisms of CYP1A1 Genes and Its Correlation with Clinical Variant of Pterygium

Background and Objective: CYP1A1 gene, which has role in carcinogenic metabolisms, is also detected in pterygium tissue. The aim of the study is to determine the polymorphisms of CYP1A1 m2 (rs1048943) and m4 (rs1799814) gene and its correlation with clinical variant of the pterygium. Methods: DNA isolation was performed from blood sample of 80 pterygium patients consisting of 40 inflammatory and 40 non-inflammatory pterygium. Genotyping of rs1048943 SNP AG (m2) in the CYP1A1 gene was performed using Alel Specific Polymerase Chain reaction (AS-PCR) and rs1048943) SNP Genotyping was performed using PCR. Polymorphism results are characterized as wild type (AA), mutant homozygote (GG), and mutant heterozygote (AG). Results: CYP1A1 m2 and m4 gene polymorphism consist of wild type (AA), mutant homozygote (GG), and mutant heterozygote (AG). Both CYP1A1 m2 and m4 genes polymorphism of both groups of inflammatory and non-inflammatory pterygium was mostly consist of wild type polymorphism, followed by the mutant heterozygote polymorphism. The wild type polymorphism was found to be higher in inflammatory pterygium, meanwhile the mutant heterozygote was found to be higher in non-inflammatory pterygium. Conclusion: There were differences in CYP1A1 m2 and m4 gene polymorphism in both pterygium group, but none has been shown to be statistically associated with the clinical variant of the pterygium.

Genetic susceptibility of CYP1A1 gene and risk of pesticide exposure in prostate cancer

BACKGROUND: The etiology of prostate cancer (PCa) is multi-factorial including environmental and genetic factors. Present study evaluates the association between level of pesticides, stress level and CYP1A1 gene polymorphism with PCa patients. METHODS: A case control study was conducted with 102 PCa patients and age match symptomatic (n= 107) and asymptomatic benign prostatic hyperplasia (BPH, n= 70) patients. Pesticide level was characterized by Gas Chromatography. The oxidative stress and scavenging mechanisms were determined by biochemical method. Two polymorphisms of CYP1A1 gene, rs4646903 and rs1048943, were analyzed by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism and allele specific PCR method. RESULTS: Higher level of pesticide namely beta-hexachlorocyclohexane (β-HCH), Malathion, Chlorpyrifos and Fenvalerate were found in PCa group (all p value: < 0.05). Kruskal Wallis H test depicted that level of β-HCH and Malathion significantly correlated with higher grade of PCa (all p< 0.05). The PCa Patients with simultaneously low antioxidant activity and high stress level tended to suffer worst clinical outcomes. Dominant model of rs4646903 and rs1048943 suggested that substitution is associated with a higher risk of PCa (OR: 2.2, CI: 1.6–3.8, p: 0.009 and OR: 1.95, CI: 1.1–3.4, p: 0.026; respectively) and this risk was also influenced by smoking and pesticide exposure. CONCLUSION: Environmental and genetic factors are reported to raise risk; person with high level of these pesticides especially in high risk genotype might be more susceptible to PCa.