Association among polymorphisms in the steroid 5α-reductase type II (SRD5A2) gene, prostate cancer risk, and pathologic characteristics of prostate tumors in an Ecuadorian population

Paz‐y‐Miño, César; Witte, Tania; Robles, Paulo; Llumipanta, William; Díaz, Myriam; Arévalo, Melissa

doi:10.1016/j.cancergencyto.2008.09.012

Cited by 21 publications

(14 citation statements)

References 24 publications

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“…Subsequently, high serum testosterone levels and low numbers of androgen receptor (AR) exon-I CAG repeats are associated with a higher HCC occurrence rate in men with chronic HBV infection [58,59]. SRD5A2, which encodes the enzyme needed to convert testosterone into dihydrotestosterone, is also associated with the occurrence of HCC [60,61].…”

Section: Genetic Polymorphism Of Host Factorsmentioning

confidence: 99%

Natural history of hepatitis B virus infection: pediatric perspective

2010

J Gastroenterol

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Hepatitis B virus (HBV) infection is an important disease globally. Chronic HBV infection may result in serious complications. Its transmission may be either perinatal or horizontal. Perinatal transmission is particularly important after the implementation of a universal vaccination program. Through either route, chronic carrier status is usually established in early childhood. The course of the disease course is determined by the host-virus interaction. The host's immune system initially tolerates the virus, and then gradually attempts to clear it. The virus, on the other hand, tries to avoid host immune system attack by a strategy involving targeted epitope mutations. By generating mutants, the virus can survive attacks from the host's immune system, enabling the infection to persist. Different individuals have different responses to HBV infection; genetic polymorphisms in cytokines, hormones, and other immune modulators may affect the final outcome of chronic HBV infection. Due to the implementation of a universal infant HBV vaccination program, HBV infection is now under control. Unfortunately, there still are some cases of vaccination failure. Very high maternal viremia, in utero infection, or escape mutants are possible reasons for vaccination failure. Immunocompromised hosts also risk vaccination failure. Blood or organ donors with occult HBV infection are possible sources for immunocompromised hosts. These victims of vaccination failure may exhibit a different disease course due to chronic HBV infection from those who acquired the infection before the universal vaccination era. The achievement of our ultimate goal of HBV elimination depends on a globally effective universal vaccination program, as well as the application of some novel successful medications to control those who are already infected.

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Section: Genetic Polymorphism Of Host Factorsmentioning

confidence: 99%

Natural history of hepatitis B virus infection: pediatric perspective

2010

J Gastroenterol

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“…Two recent examples studied SNPs related to 5α-reductase type II (SRD5A2; ref. 15) and 3β-hydroxysteroid dehydrogenase 1 (HSD3B1; ref. 16).…”

Section: Introductionmentioning

confidence: 99%

Genetic Variation of Genes Involved in Dihydrotestosterone Metabolism and the Risk of Prostate Cancer

Setlur

Chen

Hossain

et al. 2010

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Purpose: Dihydrotestosterone (DHT) is an important factor in prostate cancer (PCA) genesis and disease progression. Given PCA's strong genetic component, we evaluated the possibility that variation in genes involved in DHT metabolism influence PCA risk.Experimental Design: We investigated copy number variants (CNV) and single nucleotide polymorphisms (SNP). We explored associations between CNV of uridine diphospho-glucuronosyltransferase (UGT) genes from the 2B subclass, given their prostate specificity and/or involvement in steroid metabolism and PCA risk. We also investigated associations between SNPs in genes (HSD3B1, SRD5A1/2, and AKR1C2) involved in the conversion of testosterone to DHT, and in DHT metabolism and PCA risk. The population consisted of 426 men (205 controls and 221 cases) who underwent prostate-specific antigen screening as part of a PCA early detection program in Tyrol, Austria.Results: No association between CNV in UGT2B17 and UGT2B28 and PCA risk was identified. Men carrying the AA genotype at SNP rs6428830 (HSD3B1) had an odds ratio (OR) of 2.0 [95% confidence intervals (95% CI), 1.1-4.1] compared with men with GG, and men with AG or GG versus AA in rs1691053 (SRD5A1) had an OR of 1.8 (95% CI, 1.04-3.13). Individuals carrying both risk alleles had an OR of 3.1 (95% CI, 1.4-6.7) when compared with men carrying neither (P = 0.005). Controls with the AA genotype on rs7594951 (SRD5A2) tended toward higher serum DHT levels (P = 0.03).Conclusions: This is the first study to implicate the 5α-reductase isoform 1 (SRD5A1) and PCA risk, supporting the rationale of blocking enzymatic activity of both isoforms of 5α-reductase for PCA chemoprevention.

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“…Furthermore, after stratified analyses by ethnicity and source of control, a similar association was also found in Latinos, other-ethnicity, population-based, and hospital-based subgroups under corresponding genetic models. Although in terms of Latino groups the data are distinguished between the studies of Pearce et al [28] and Paz-y-Mino et al [31] , no substantial heterogeneity was found between the studies (Fig. 3).…”

Section: Discussionmentioning

confidence: 93%

Relationship between SRD5A2 rs9282858 polymorphism and the susceptibility of prostate cancer

Fang

Guo²,

Chen³

et al. 2017

Medicine

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The pathogenetic mechanism of prostate cancer (PCa) has not been understood completely, and gene polymorphisms have been demonstrated to play a critical role in the course. It has been reported that rs9282858 polymorphism of steroid 5-α-reductase type 2 (SRD5A2) may affect the susceptibility of PCa, but some researches showed different results. We therefore carried out a meta-analysis to clarify this relationship.Relevant studies were identified through PubMed and Chinese National Knowledge Infrastructure databases concerning the association between SRD5A2 rs9282858 polymorphism and PCa. Odds ratios (ORs) with their 95% confidence intervals (95% CIs) were calculated to assess the strength of the association. Additionally, stratified analyses were performed based on ethnicity and source of control. Besides, heterogeneity test, sensitivity analysis, and publication bias evaluation were conducted in current meta-analysis as well.Ultimately, 20 publications incorporating 30 case-control studies were included in this meta-analysis, involving a total of 7300 cases and 7952 controls. The overall results demonstrated that SRD5A2 rs9282858 polymorphism was remarkably associated with increased susceptibility of PCa (TT vs. AA: OR = 4.08, 95% CI = 1.94–8.58; TT + AT vs. AA: OR = 1.28, 95% CI = 1.11–1.47; TT vs. AA + AT: OR = 4.44, 95% CI = 2.12–9.27; allele T vs. allele A: OR = 1.34, 95% CI = 1.17–1.54). After subgroup analyses by ethnicity and source of control, we also observed a similar trend in Latinos, other-ethnicity, population-based, and hospital-based groups under corresponding genetic models.Our findings indicate that SRD5A2 rs9282858 polymorphism may be a susceptible factor to PCa.

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Association among polymorphisms in the steroid 5α-reductase type II (SRD5A2) gene, prostate cancer risk, and pathologic characteristics of prostate tumors in an Ecuadorian population

Cited by 21 publications

References 24 publications

Natural history of hepatitis B virus infection: pediatric perspective

Natural history of hepatitis B virus infection: pediatric perspective

Genetic Variation of Genes Involved in Dihydrotestosterone Metabolism and the Risk of Prostate Cancer

Relationship between SRD5A2 rs9282858 polymorphism and the susceptibility of prostate cancer

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