Single and Multigenic Analysis of the Association between Variants in 12 Steroid Hormone Metabolism Genes and Risk of Prostate Cancer

Beuten, Joke; Gelfond, Jonathan; Franke, Jennifer L.; Weldon, Korri; Crandall, AnaLisa C.; Johnson‐Pais, Teresa L.; Thompson, Ian M.; Leach, Robin J.

doi:10.1158/1055-9965.epi-09-0076

Cited by 83 publications

(81 citation statements)

References 55 publications

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“…Therefore, at least in the early stages of PC, 3b-Adiol formation may shift the equilibrium versus a slowing down of progression and invasiveness of the tumor cells. This exciting hypothesis has strong support in clinical observations, demonstrating that genetic alteration of several enzymes involved in androgenic steroid metabolism is linked to hereditary and sporadic PC susceptibility (Chang et al 2002, Steckelbroeck et al 2004, Bauman et al 2006, Cunningham et al 2007, Neslund-Dudas et al 2007, Park et al 2007, Ross et al 2008, Beuten et al 2009, Mindnich & Penning 2009). It has been established that enzyme responsible for 3b-Adiol formation from the DHT in prostate is AKR1C1; in fact, AKR1C1:AKR1C2 (responsible for 3a-diol formation from the DHT) transcript ratio fells in PC; thus, the data here presented provide clear explanations of these observations, since the reduction of 3b-Adiol levels in favor of 3a-Adiol may be a risk factor for PC in these patients, because the 3b-Adiol 'protective' effect will obviously disappear.…”

Section: Discussionmentioning

confidence: 88%

Estrogen receptor β and the progression of prostate cancer: role of 5α-androstane-3β,17β-diol

Dondi

Piccolella²,

Biserni³

et al. 2010

Endocrine-Related Cancer

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Prostate cancer (PC) develops in response to an abnormal activation of androgen receptor induced by circulating androgens and, in its initial stages, is pharmacologically controlled by androgen blockade. However, androgen ablation therapy often allows androgen-independent PC development, generally characterized by increased invasiveness. We previously reported that 5a-androstane-3b,17b-diol (3b-Adiol) inhibits the migration of PC cell lines via the estrogen receptor b (ERb) activation. Here, by combining in vitro assays and in vivo imaging approaches, we analyzed the effects of 3b-Adiol on PC proliferation, migration, invasiveness, and metastasis in cultured cells and in xenografts using luciferase-labeled PC3 (PC3-Luc) cells. We found that 3b-Adiol not only inhibits PC3-Luc cell migratory properties, but also induces a broader anti-tumor phenotype by decreasing the proliferation rate, increasing cell adhesion, and reducing invasive capabilities in vitro. All these 3b-Adiol activities are mediated by ERb and cannot be reproduced by the physiological estrogen, 17b-estradiol, suggesting the existence of different pathways activated by the two ERb ligands in PC3-Luc cells. In vivo, continuous administration of 3b-Adiol reduces growth of established tumors and counteracts metastasis formation when PC3-Luc cells are engrafted s.c. in nude mice or are orthotopically injected into the prostate. Since 3b-Adiol has no androgenic activity, and cannot be converted to androgenic compounds, the effects here described entail a novel potential application of this agent against human PC.

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Section: Discussionmentioning

confidence: 88%

Estrogen receptor β and the progression of prostate cancer: role of 5α-androstane-3β,17β-diol

Dondi

Piccolella²,

Biserni³

et al. 2010

Endocrine-Related Cancer

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“…In this context, the effect of a single polymorphism is unlikely to be substantial in studies of complex diseases. Thus, the approach based on combining multiple polymorphisms that interact in the same pathway may amplify the effect of single variants and enhance the predictive power of polymorphism analysis for multifactorial disease (24,25). Here, we have investigated the influence of multiple RET variants, isolated or in combination, in the estimated risk for MTC as well as in its clinical presentation.…”

Section: Introductionmentioning

confidence: 99%

Additive effect of RET polymorphisms on sporadic medullary thyroid carcinoma susceptibility and tumor aggressiveness

Ceolin

Siqueira²,

Ferreira³

et al. 2012

European Journal of Endocrinology

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Objective: RET single nucleotide polymorphisms (SNPs) have been implicated in the pathogenesis and progression of medullary thyroid carcinoma (MTC). Here, we investigated the influence of multiple RET variants (G691S, L769L, S836S, and S904S) on the risk of MTC and tumor behavior. Design and methods: One hundred and seven MTC patients and 308 cancer-unaffected control individuals were included. SNPs were analyzed using Custom TaqMan Genotyping Assays. Haplotypes based on the combination of allelic variants were inferred using a Bayesian statistical method. Results: The minor allele frequencies in MTC patients were as follows: L769L: 28.0%, S836S: 8.9%, and G691S/S904S: 22.2%. The RET L769L and S836S SNPs were associated with increased risk of MTC (odds ratio (OR)Z1.95, 95% CI: 1.2-3.1, PZ0.005 and ORZ2.29, 95% CI: 1.2-4.5, PZ0.017 respectively). The adjusted OR for individuals harboring haplotypes with three or more polymorphic alleles was 3.79 (95% CI: 1.5-9.5; PZ0.004), indicating an additive effect of these variants on the risk for MTC. Among MTC patients, no significant associations were observed between RET variants and age of diagnosis or tumor size but serum calcitonin levels increased according to the number of risk alleles (PZ0.003). Remarkably, patients carrying haplotypes with three or four risk alleles had increased risk for lymph node and distant metastases at diagnosis (ORZ5.84, 95% CI: 1.1-31.2, PZ0.039). Further analysis using Kaplan-Meier model demonstrated that metastatic disease occurred earlier in individuals harboring multiple risk alleles. Conclusion: Our results demonstrated an additive effect of RET polymorphic alleles on the estimated risk of developing aggressive MTC.

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“…On the basis of the 14 articles that were identified as providing information relevant to the assessment of the clinical validity of SNP panels, reported overall (i.e., including genetic markers included in the panels and variants of other genes) genotyping accuracy rates ranged up to >99.9%; SNP call rates were usually reported in the range of 98 to 99% (with a low of 89%), and reported concordance upon retesting was usually >99%. 25,[34][35][36][37][38][39][40][41][42][43][45][46][47][48][49][50][51][53][54][55] However, the methodologies described as the basis for determining analytical validity were not uniform across all analytes for some panels; in multiple cases, the SNP call rate of a given test panel was reported on the basis of data from two or more different chip platforms or analytical techniques. No evidence was identified about sources of variation in accuracy or analytical validity across different test platforms.…”

Section: Resultsmentioning

confidence: 99%

Multigene panels in prostate cancer risk assessment: a systematic review

Little

Wilson

Carter

et al. 2016

Genetics in Medicine

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Prostate cancer is the fourth most common malignancy worldwide, and the second most common among men.1 In 2014, it was estimated that more than a quarter of a million new cases were diagnosed in North America and that the disease accounted for more than 33,000 deaths. 2,3 These numbers are likely to increase with the aging of the population. On the basis of data from the Surveillance, Epidemiology, and End Results program, more men were diagnosed with prostate cancer at a younger age and earlier stage in 2004-2005 than in the mid-late 1990s, and disparity between ethnic groups in cancer stage at diagnosis decreased. 4 Apart from age, 5 ethnic group, 5,6 and family history, 7-9 the risk factors associated with prostate cancer are unclear, 5 making primary prevention difficult. Prostate cancer is currently considered to be a complex, multifactorial disease, and the vast majority of familial clustering is attributed to the interaction of multiple shared susceptibility genes with moderate to low penetrance and shared environmental factors within these families.The natural history of prostate cancer is highly variable. 10 In a large proportion of men the disease is indolent, and it is difficult to predict which tumors will be aggressive. The value of aggressive management for localized prostate cancer is debated, [11][12][13][14] and only a small proportion of men with early-stage prostate cancer die from the disease within 10 to 15 years of diagnosis. Developing tools to differentiate aggressive and indolent disease is of key importance.Prostate-specific antigen (PSA) screening was introduced in the late 1980s.15 Meta-analyses of seven randomized controlled trials (RCTs) of screening using PSA testing alone or in combination with digital rectal examination suggested no evidence of benefit in reducing mortality 16,17 and some evidence of harm from overdiagnosis.17 Amid substantial debate, 18-20 the argument has been made for developing more accurate screening tests, including possible genetic markers. Purpose: Single-nucleotide polymorphism (SNP) panel tests have been proposed for use in the detection of, and prediction of risk for, prostate cancer and as prognostic indicator in affected men. A systematic review was undertaken to address three research questions to evaluate the analytic validity, clinical validity, clinical utility, and prognostic validity of SNP-based panels.Methods: Data sources comprised MEDLINE, Cochrane CEN-TRAL, Cochrane Database of Systematic Reviews, and EMBASE; these were searched from inception to April 2013. The gray-literature searches included contact with manufacturers. Eligible studies included English-language studies evaluating commercially available SNP panels. Study selection and risk of bias assessment were undertaken by two independent reviewers. Results:Twenty-one studies met eligibility criteria. All focused on clinical validity and evaluated 18 individual panels with 2 to 35 SNPs.All had poor discriminative ability (overall area under receiver-operator characteristic curves, 5...

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Single and Multigenic Analysis of the Association between Variants in 12 Steroid Hormone Metabolism Genes and Risk of Prostate Cancer

Cited by 83 publications

References 55 publications

Estrogen receptor β and the progression of prostate cancer: role of 5α-androstane-3β,17β-diol

Estrogen receptor β and the progression of prostate cancer: role of 5α-androstane-3β,17β-diol

Additive effect of RET polymorphisms on sporadic medullary thyroid carcinoma susceptibility and tumor aggressiveness

Multigene panels in prostate cancer risk assessment: a systematic review

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