Genetic polymorphism in sex hormone metabolism and prostate cancer risk

Erşekerci, Erol; Sofikerim, Mustafa; Taheri, Serpil; Demirtaş, Abdullah; Halis, Fikret

doi:10.4238/2015.july.3.8

Cited by 6 publications

(5 citation statements)

References 27 publications

(30 reference statements)

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“…Nevertheless, in a study performed among Turkish men, an apparent elevation in BPH risk was found in those with the T allele of SRD5A2 rs9282858 polymorphism, but the rs523349 polymorphism was detected to have no significant influence on the disease risk (Izmirli et al, 2011 ). Similarly, another study by Ersekerci et al among Turkish men as well, showed no significant difference in genotype or allele distribution of rs523349 polymorphism between case and control groups (Ersekerci et al, 2015 ). A study by Li et al found no apparent linkage between the two SNPs and BPH in a Japanese population either (Li et al, 2003 ).…”

Section: Discussionmentioning

confidence: 87%

“…Among the remaining 58 articles, 27 had no control group, 14 were not associated with SRD5A2 polymorphisms, 5 were drug dose researches, 2 were duplicate reports, and another 2 contained insufficient data. As a result, 1,865 cases and 1,424 controls were included in the present meta-analysis (Li et al, 2003 ; Giwercman et al, 2005 ; Salam et al, 2005 ; Das et al, 2008 ; Rajender et al, 2009 ; Izmirli et al, 2011 ; Choubey et al, 2015 ; Ersekerci et al, 2015 ). Characteristics of the included studies are provided in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

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Association between SRD5A2 rs523349 and rs9282858 Polymorphisms and Risk of Benign Prostatic Hyperplasia: A Meta-Analysis

Zeng

et al. 2017

Front. Physiol.

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Objective: Previous studies have reported that rs523349 (V89L) and rs9282858 (A49T) polymorphisms in the gene 5α-reductase II (SRD5A2) are associated with the risk of benign prostatic hyperplasia (BPH), but different opinions have emerged. In view of distinct discrepancies among those findings, we performed this meta-analysis to ascertain a more accurate association between SRD5A2 rs523349 and rs9282858 polymorphisms and the risk of BPH.Methods: Studies investigating the association between SRD5A2 rs523349 and rs9282858 polymorphisms and susceptibility to BPH were searched from the databases of PubMed, Embase, Wanfang, and Chinese National Knowledge Infrastructure (CNKI).The strength of correlation was assessed by crude odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs). Moreover, subgroup analysis was conducted to further ascertain such relationship and investigate sources of heterogeneity.Results: SRD5A2 rs9282858 (A49T) polymorphism showed a significant correlation with increased BPH susceptibility under allele T vs.allele A genetic model (OR = 2.51, 95% CI = 1.29–4.88) in total analysis, and stratification analysis by ethnicity also revealed a similar association in Caucasian group under the same contrast. SRD5A2 rs523349 (V89L) polymorphism showed no significant role in BPH occurrence in total analysis, but its reducing and increasing effects on the disease risk were reflected in Caucasian and other-ethnicity subgroups, respectively, after stratification analysis by ethnicity.Conclusion: In conclusion, SRD5A2 rs9282858 polymorphism may elevate the susceptibility to BPH, while the polymorphism rs523349 may exert different influences on the disease in people of different ethnic lines.

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Section: Discussionmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Association between SRD5A2 rs523349 and rs9282858 Polymorphisms and Risk of Benign Prostatic Hyperplasia: A Meta-Analysis

Zeng

et al. 2017

Front. Physiol.

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“…, which is through CYP19A1 SNPs, especially through increasing the genotype TT of the rs700518 gene expression, which causes the metabolism level of estrogen to increase, leading to a reduction in the T/E ratio; this triggers IR, raises blood glucose levels, and promotes hyperplasia of prostate gland acinar cells and stromal cells in the prostate tissue, leading to the occurrence of clinical BPH and MetS. In contrast, BPH can lead to a systemic metabolic disorder, which can lead to IR, resulting in MetS (Crawford et al ., ; Balistreri et al ., ; Ersekerci et al ., ; Cornu et al ., ). Moreover, through IR, MetS and BPH interact and progress clinically.…”

Section: Discussionmentioning

confidence: 99%

The single nucleotide polymorphism rs700518 is an independent risk factor for metabolic syndrome and benign prostatic hyperplasia (MetS‐BPH)

et al. 2018

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Studies have shown that 48.59% of benign prostate hyperplasia (BPH) is combined with metabolic syndrome (MetS). The mainstream view supports the correlation between MetS and BPH, but the pathogenesis of MetS-BPH is not fully understood. Four hundred and seventy-four men, aged 47 years or older, were recruited into this study by consecutive routine physical examination programs, and several parameters were obtained from each participant. Based on the diagnosis of BPH, MetS, and MetS-BPH, the participants were divided into BPH and Non-BPH groups, MetS and Non-MetS groups, as well as MetS-BPH and Non-MetS-BPH groups. The values of the obtained parameters were evaluated using Student's t-test, chi-square test, and logistic regression analysis. The value of estradiol (E2) was higher in the diseased groups (BPH, MetS, and MetS-BPH groups) compared with the corresponding control groups (Non-BPH, Non-MetS, and Non-MetS-BPH groups), and the differences were statistically significant. Also, E2 had an independent association with BPH (OR = 2.286, 95% CI: 1.723-3.593, p < 0.001), MetS (OR = 1.406, 95% CI: 0.585-2.315, p < 0.001), and MetS-BPH (OR = 1.249, 95% CI: 0.795-1.962, p < 0.001). Regarding SNPs of CYP19A1 gene, both the rs4646 genotypes (CC, CA, and AA) and the rs700518 genotypes (CC, CT, and TT) were present in every group, and all genotypes had statistically significant differences between the diseased and corresponding control groups. However, only the TT genotype of rs700518 was independently associated with BPH, MetS, and MetS-BPH after adjusting for age. The TT genotype of rs700518 is an independent risk factor for the MetS-BPH populations, and the CYP19A1 gene regulation of estrogen leads to MetS-BPH.

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“…A study recently reported on two populations of African ancestry failed to show any association between rs60271534 and prostate cancer risk [17]. Another SNP 1531 C > T was investigated in the Turkish prostate cancer patients, but no significant association was observed [102]. Lévesque et al [103] reported a study in which results obtained in Caucasians and Taiwanese were compared.…”

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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Genetic polymorphism in sex hormone metabolism and prostate cancer risk

Abstract: ABSTRACT. We compared single-nucleotide polymorphisms for point mutations in cytochrome P450 genes, including cytochrome P450c17α (CYP17), cytochrome P450 aromatase (CYP19), steroid-5-a-reductase (SRD5A2), and prostate-specific antigen (PSA) involved in androgen and estrogen production.

Cited by 6 publications

References 27 publications

Association between SRD5A2 rs523349 and rs9282858 Polymorphisms and Risk of Benign Prostatic Hyperplasia: A Meta-Analysis

Association between SRD5A2 rs523349 and rs9282858 Polymorphisms and Risk of Benign Prostatic Hyperplasia: A Meta-Analysis

The single nucleotide polymorphism rs700518 is an independent risk factor for metabolic syndrome and benign prostatic hyperplasia (MetS‐BPH)

Genetic Polymorphisms in Aromatase (CYP19) Gene and Cancer

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