Polymorphisms in androgen metabolism genes AR, CYP1B1, CYP19, and SRD5A2and prostate cancer risk and aggressiveness in Bulgarian patients

Kachakova, Darina; Mitkova, A.; Popov, Elenko; Beltcheva, Olga; Vlahova, A.; Dikov, Tihomir; Christova, S.; Mitev, Vanio; Slavov, Chavdar; Kaneva, Radka

doi:10.3906/sag-1501-124

Cited by 8 publications

(20 citation statements)

References 34 publications

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“…Recently microarray data from the livers of the CYP1B1 KO mice that are resistant to diet-induced obesity indicated that CYP1B1 deletion substantially alters the expression of genes associated with fatty acid homeostasis [33]. Several studies have examined the relationship between individual CYP1B1 polymorphisms and cancer risk [14,15,[34][35][36][37]. However, very limited data are available for CYP1B1*2 (rs1056827G>T) genetic variants in T2D.…”

Section: Discussionmentioning

confidence: 99%

Cytochrome P450 Cyp1b1*2 Gene and Its Association With T2d in Tabuk Population, Northwestern Region of Saudi Arabia

Elfaki

Almutairi

Mir

et al. 2018

Asian J Pharm Clin Res

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Objective: Cytochrome P450 1B1 (CYP1B1) is involved in the activation of procarcinogens and steroid metabolism. Genetic variants of CYP1B1 are associated with altered catalytic activity and disease phenotypes. The purpose of this study was to investigate the role of CYP1B1 (rs1056827) polymorphism in inducing T2D. Methods:This cross-sectional study enrolled 113 subjects of T2D and 120 controls. DNA was isolated from blood. Genotyping of the rs1056827 was done by allele-specific polymerase chain reaction. The frequency of alleles and genotype distribution was compared in T2D cases and healthy controls. Statistical analysis was performed with SPSS, Chi-square, and Fisher exact test. Hardy-Weinberg equilibrium was tested by a χ 2 test. The associations between rs1056827 variant genotypes and T2D were estimated by computing the odds ratios and their 95% confidence intervals (CI) from univariate and multivariate logistic regression analysis.Results: A significant association of rs1056827 was found between T2D cases and controls (p<0.0001). When GG genotype was compared with GT genotype a significant association was found with odd ration ( Conclusion:This result suggests a significant association between rs1056827G>T polymorphism and T2D. This finding is limited due to the smaller sample size and can be validated by large sample size studies.

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Section: Discussionmentioning

confidence: 99%

Cytochrome P450 Cyp1b1*2 Gene and Its Association With T2d in Tabuk Population, Northwestern Region of Saudi Arabia

Elfaki

Almutairi

Mir

et al. 2018

Asian J Pharm Clin Res

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“…According to the inclusion and exclusion criteria, a total of 14 studies [14,[16][17][18][19][24][25][26][27][28][29][30][31][32] were deemed eligible for this meta-analysis ( Figure 1 detailed the study selection process). Among them, 8 studies investigated only the Arg264Cys polymorphism [14, 16-18, 24-26, 28], 5 studies explored only the (TTTA)n repeat polymorphism [19,[29][30][31][32], and 1 study focused on both polymorphisms [27]. The main characteristics of these studies are listed in Supplementary Table 1 (see Additional le 1) and…”

Section: Selection and Characteristics Of Eligible Studiesmentioning

confidence: 99%

The CYP19A1 (TTTA)n repeat polymorphism, but not Arg264Cys polymorphism, may affect the risk of prostate cancer: evidence from a meta-analysis

Guo¹,

Liu²,

Liu³

et al. 2020

Preprint

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Background: Abnormal aromatase (CYP19A1) expression has been proposed to take part in the carcinogenesis of prostate cancer (PCa).However, results of studies on the CYP19A1 gene polymorphisms and PCa are conflicting.This meta-analysis aimed to systematically evaluate the association between the CYP19A1 Arg264Cys polymorphism and (TTTA)n repeat polymorphism and PCa.Methods: Electronic databases (PubMed, EmBase, ScienceDirect, and Cochrane Library) were comprehensively searched to identify eligible studies. The strength of association between the CYP19A1 Arg264Cys polymorphism and PCa was assessed by pooled odds ratio (OR) and 95% confidence interval (95% CI) in allelic, dominant, recessive, homozygous, and heterozygous genetic models. To analyze the impact of the (TTTA)n repeat polymorphism, we took sequentially the N-repeat allele (where N equals 7,8,10,11,12, and 13) as the minor allele and the sum of all the other alleles as the major allele. The ORs and 95%CIs were calculated in the allelic model; this analysis was performed individually for each repeat number.Results: Pooled estimates of nine eligible studies addressing the Arg264Cys polymorphism indicated that this polymorphism was not associated with the risk of PCa in the overall population and in the Caucasian and Asian subgroups. A meta-analysis of six studies addressing the (TTTA)n repeat polymorphism revealed that the 8-repeat allele increased PCa risk in the overall population (OR=1.34, 95% CI=1.14–1.58, P=0.001) and in the subgroup with population-based (PB) controls (OR=1.41, 95% CI=1.13–1.74, P=0.002). Conclusions: The meta-analysis indicated that the CYP19A1 (TTTA)n repeat polymorphism, but not Arg264Cys polymorphism may affect PCa risk.

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“…This SNP is a C > T transition in exon 7 of CYP19A1 gene and results in the substitution of Arg at position 264 by Cys. No association was reported among Bulgarians [94], African Americans [95], and Japanese [96]. However, a study on North Indian population showed that the variant Cys was associated with statistically significant increased risk of prostate cancer (OR = 2.28; 95% CI = 1.20-4.35; p = 0.012) [97].…”

Section: Variations In Cyp19a1 Gene and Prostate Cancermentioning

confidence: 99%

“…The coexisting ins allele and (TTTA)12 also in the CYP19A1 reduced the risk of developing prostate cancer. More recently, Kachakova et al [94] have shown that the 7/8 genotype of (TTTA)n repeat polymorphism in CYP19A1, when coexisting with the C allele of rs1056837 in CYP1B1, predisposes to prostate cancer, while the 8/9 and the 7/12 genotypes of (TTTA)n of CYP19A1 when existing with the C allele of CYP1B1 associate with lower risk of prostate cancer and a reduced risk for aggressive disease.…”

Section: Variations In Cyp19a1 Gene and Prostate Cancermentioning

confidence: 99%

Genetic Polymorphisms in Aromatase (CYP19) Gene and Cancer

Warsy¹,

Al-Mukaynizi²,

Al-Daihan³

et al. 2017

Genetic Polymorphisms

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Estrogens play an important role in the development and progression of several types of cancers. The synthesis of estrogens occurs in almost all tissues of the body in addition to the gonads. The enzyme aromatase (CYP19A1) encoded by CYP19A1 gene is involved in the synthesis of estrogens. Genetic variations in CYP19A1 gene influence both the structure-function relationship of the enzyme and the rate of its synthesis. Extensive studies have reported different types of polymorphisms in the CYP19A1 gene and have shown that the polymorphisms, depending on their location in the gene, have different effects on the function and activity of the gene product. Association studies have been conducted and have led to the realization that interpopulation differences are widespread. Not only do polymorphic forms exert different effects on the development of different cancers, due possibly to the influence of other genetic variations, environmental, metabolic, and epigenetic factors, but also are important as they lead to the interindividual differences seen during treatment of the cancer state. This chapter covers important aspects of the aromatase function, the CYP19A1 gene structure, polymorphisms identified in the gene, different cancers and associated polymorphisms, and the role of the polymorphic forms in affecting the treatment strategies.

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Polymorphisms in androgen metabolism genes AR, CYP1B1, CYP19, and SRD5A2and prostate cancer risk and aggressiveness in Bulgarian patients

Cited by 8 publications

References 34 publications

Cytochrome P450 Cyp1b1*2 Gene and Its Association With T2d in Tabuk Population, Northwestern Region of Saudi Arabia

Cytochrome P450 Cyp1b1*2 Gene and Its Association With T2d in Tabuk Population, Northwestern Region of Saudi Arabia

The CYP19A1 (TTTA)n repeat polymorphism, but not Arg264Cys polymorphism, may affect the risk of prostate cancer: evidence from a meta-analysis

Genetic Polymorphisms in Aromatase (CYP19) Gene and Cancer

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