Prevalence and Prognostic Value of the Polymorphic Variant 1245A&gt;C of HSD3B1 in Castration-resistant Prostate Cancer

Stangl‐Kremser, Judith; Lemberger, Ursula; Hassler, Melanie R.; Bruchbacher, Andreas; Ilijazi, Dafina; Garstka, Nathalie; Kramer, Gero; Haitel, Andrea; Abufaraj, Mohammad; Shariat, Shahrokh F.

doi:10.1016/j.clgc.2019.06.012

Cited by 4 publications

(5 citation statements)

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“…The results suggested that these variants of the HSD3B1 steroidogenic enzyme gene could be a powerful new biomarker capable of identifying patients with aggressive disease who warrant early escalated therapy and in clinical management of the disease. Additionally, the data obtained and suggestions were matched with literature about the role of this enzyme in the degradation of DHT ( 61 ) and malfunction in accumulation of DHT in prostatic tissue ( 62 , 63 ).…”

Section: Discussionmentioning

confidence: 70%

Role of single nucleotide polymorphisms of the HSD3B1 gene (rs6203 and rs33937873) in the prediction of prostate cancer risk

et al. 2022

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3-β-hydroxysteroid dehydrogenase 1 (HSd3B1) is shown to affect dihydrotestosterone level in prostatic tissue which is a risk factor for prostate cancer (Pc). The present study aimed to determine whether rs33937873 (G313a) and rs6203 (c338T) single nucleotide polymorphisms (SnP) in HSd3B1 gene was a potential risk factor for Pc susceptibility and can predict the recurrence of Pc in egyptian patients. a total of 186 egyptian patients were selected with incident primary Pc and compared with 180 age healthy controls. The frequencies and the main effect of rs33937873 and rs6203 in HSd3B1 were compared and investigated between the patients and control using genotyping technique and statistical analysis. The mutant Ga genotype of G313a in rs33937873 SnP was considered as an independent risk for Pc in the multivariate regression analysis [odds ratio (OR)=2.7, 95% confidence intervals (CI): 1.2-5.5, P=0.01] together with positive history of hypertension (HTn) (or=6.2, 95% ci: 3.2-12.1, P=0.0001) and begin prostatic hyperplasia (BPH; or=8.9, 95% ci: 4.5-17.5, P=0.0001). conversely, in rs6203 (c338T), c allele is considered as major risk allele in the development of Pc (or=1.8, P=0.0003). The univariate logistic regression analyses indicated that cc genotype of rs6203 was a Pc risk factor (or=1.9, 95% ci: 1.3-2.9, P=0.002). in addition, the frequency of the a-c haplotype established by rs33937873-rs6203 was also significantly higher for PC (P= 0.013). The predication of Pc recurrence was associated only with positive family history (or=7.7, 95% ci: 2.3-25.9, P=0.001) and not for The G313a and c338T SnPs. These results suggested that the two HSd3B1 polymorphisms rs33937873 and rs6203 may modify the risk of Pc, particularly among patients with HTn and history of BPH, suggesting them as prominent future markers for prediction of Pc risk.

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Section: Discussionmentioning

confidence: 70%

Role of single nucleotide polymorphisms of the HSD3B1 gene (rs6203 and rs33937873) in the prediction of prostate cancer risk

et al. 2022

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“…The former concluded that there was no relation between HSD3B1(1245C) and survival outcome of CRPC [24] . Similarly, the latter reported that HSD3B1(1245C) was related to a trend of worse prognosis for CRPC because of increased tumor expression of cell proliferation and cell cycle genes [23] , but without significant difference.…”

Section: Impact Of Hsd3b1(1245c) On the Other Medical Management Is Waiting To Definementioning

confidence: 86%

“…Except the outcome in the primary cohort of the Hearn's study in 2016 [17] , HSD3B1(1245C) was noted to have no impact on the mortality of CSPC. At a more fundamental level, Chen et al [23] reported that HSD3B1 was marginally significantly associated with impaired survival outcome. Based on the study by Hearn et al [21] , the effect of HSD3B1 was only found in patients with low-volume PCa.…”

Section: Hsd3b1(1245c) Promotes Resistance To Adt and Development To Crpcmentioning

confidence: 99%

“…Stangl-Kremser et al [24] and Chen et al [23] both summarized the association between HSD3B1(1245C) and survival outcome of patients with CRPC via genetic sequencing of prostate tissue. The former concluded that there was no relation between HSD3B1(1245C) and survival outcome of CRPC [24] .…”

Section: Impact Of Hsd3b1(1245c) On the Other Medical Management Is Waiting To Definementioning

confidence: 99%

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The association between genetic variants in HSD3B1 and clinical management of PCa

Huang¹,

Huang²,

Na³

2021

jtgg

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Androgen is an important factor in the occurrence and progression of prostate cancer. The principal clinical strategy is androgen deprivation therapy (ADT). However, progression to castrate-resistant prostate cancer (CRPC) is almost inevitable to occur after ADT. One of the key mechanisms is the intertumoral synthesis of androgen where 3β-hydroxysteroid dehydrogenase isoenzyme-1 (3βHSD1, encoded by HSD3B1) catalyzes the ratelimiting step. A germline missense-encoding variant of HSD3B1(1245A>C, rs1047303) has been the focus of research because HSD3B1(1245C) works as an adrenal-permissive allele and encodes a more stable enzyme that promotes the synthesis of androgen. Several studies were performed to explore the role of HSD3B1(1245C) in the development of CRPC and the outcome of clinical management. Thus, we searched the published research articles using the keywords "prostate cancer" and "HSD3B1", in PubMed and Embase database. After reviewing the abstracts and full articles, 16 original research articles from 45 search results were finally selected and reviewed. Based on the current evidence, HSD3B1(1245C) is proposed to accelerate ADT resistance and the development of CRPC. It is also associated with a poorer prognosis of PCa treated with ADT. However, due to conflicting results, the association between HSD3B1(1245C) and the effect of next-generation hormone therapy (i.e., abiraterone) for patients with CRPC is not clear enough. In conclusion, HSD3B1(1245C) has value for predicting the outcome of PCa and potential to be involved in therapeutic decision making.

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“…To facilitate treatment decisions, different biomarkers have been developed and evaluated. These markers include a variety of routine laboratory markers, alterations in circulating cell-free DNA or genomic sequencing of tumor tissues (Stangl-Kremser et al 2019 ; Neeb et al 2021 ). However, the latter are cost- and time-expensive.…”

Section: Introductionmentioning

confidence: 99%

Systemic inflammatory biomarkers as predictive and prognostic factors in men with metastatic castration-refractory prostate cancer treated with docetaxel therapy: a comprehensive analysis in a German real-world cohort

Neuberger

Goly

Skladny

et al. 2022

J Cancer Res Clin Oncol

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Purpose Advances in therapy of metastatic castration-refractory prostate cancer (mCRPC) resulted in more therapeutic options and led to a higher need of predictive/prognostic biomarkers. Systemic inflammatory biomarkers could provide the basis for personalized treatment selection. This study aimed to assess the modified Glasgow Prognostic Score (mGPS), the neutrophile-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR) and the systemic immune-inflammation index (SII) in men with mCRPC under docetaxel. Methods Patients with mCRPC and taxane chemotherapy at a tertiary care centre between 2010 and 2019 were screened retrospectively. The biomarkers mGPS, NLR, PLR and SII were assessed and analyzed for biochemical/radiologic response and survival. Results We included 118 patients. Of these, 73 (61.9%) had received docetaxel as first-line, 31 (26.2%) as second-line and 14 (11.9%) as third-line treatment. For biochemical response, mGPS (odds ratio (OR) 0.54, p = 0.04) and PLR (OR 0.63, p = 0.04) were independent predictors in multivariable analysis. SII was significant in first-line cohort only (OR 0.29, p = 0.02). No inflammatory marker was predictive for radiologic response. In multivariable analysis, mGPS and NLR (hazard ratio (HR) 1.71 and 1.12, both p < 0.01) showed significant association with OS in total cohort and mGPS in the first-line cohort (HR 2.23, p < 0.01). Haemoglobin (Hb) and alkaline phosphatase (AP) showed several significant associations regarding 1 year, 3 year, OS and biochemical/radiologic response. Conclusions Pre-treatment mGPS seems a promising prognostic biomarker. A combination of mGPS, NLR and further routine markers (e.g., Hb and AP) could yield optimized stratification for treatment selection. Further prospective and multicentric assessment is needed.

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Prevalence and Prognostic Value of the Polymorphic Variant 1245A>C of HSD3B1 in Castration-resistant Prostate Cancer

Cited by 4 publications

References 12 publications

Role of single nucleotide polymorphisms of the HSD3B1 gene (rs6203 and rs33937873) in the prediction of prostate cancer risk

Role of single nucleotide polymorphisms of the HSD3B1 gene (rs6203 and rs33937873) in the prediction of prostate cancer risk

The association between genetic variants in HSD3B1 and clinical management of PCa

Systemic inflammatory biomarkers as predictive and prognostic factors in men with metastatic castration-refractory prostate cancer treated with docetaxel therapy: a comprehensive analysis in a German real-world cohort

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