The PROFILE Feasibility Study: Targeted Screening of Men With a Family History of Prostate Cancer

Castro, Elena; Mikropoulos, Christos; Bancroft, Elizabeth; Dadaev, Tokhir; Goh, Chee; Taylor, Natalie; Saunders, Ed; Borley, Nigel; Keating, Diana; Page, Elizabeth; Saya, Sibel; Hazell, Stephen; Livni, Naomi; deSouza, Nandita M.; Neal, David E.; Hamdy, Freddie C.; Kumar, Pardeep; Antoniou, Antonis C.; Kóte-Jarai, Zsofia; Eeles, Rosalind

doi:10.1634/theoncologist.2015-0336

Cited by 29 publications

(22 citation statements)

References 24 publications

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“…Indeed, calculation of a genetic risk score using the SNPs genotyped in this study allows for the stratification of risk for PCa across a 5‐fold range, ie, men who are in the upper 10% of risk allele carriers are ∼5‐fold more likely to be diagnosed with prostate cancer than men in the lowest 10%. This level of risk is sufficient to warrant consideration of genetic risk estimate calculations for targeted early screening in the general population . The use of SNPs to identify men in the Norwegian population who are at increased inherited risk for PCa and thus would benefit from early disease screening and monitoring could eventually result in significant declines in mortality and morbidity in these men.…”

Section: Discussionmentioning

confidence: 99%

“…This level of risk is sufficient to warrant consideration of genetic risk estimate calculations for targeted early screening in the general population. 19 The use of SNPs to identify men in the Norwegian population who are at increased inherited risk for PCa and thus would benefit from early disease screening and monitoring could eventually result in significant declines in mortality and morbidity in these men.…”

Section: Discussionmentioning

confidence: 99%

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Genetic factors influencing prostate cancer risk in Norwegian men

et al. 2017

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Norway has one of the highest rates of death due to prostate cancer (PCa) in the world. To assess the contribution of both common and rare single nucleotide variants (SNPs) to the prostate cancer burden in Norway, we assessed the frequency of the established prostate cancer susceptibility allele, HOXB13 G84E, as well as a series of validated, common PCa risk SNPs in a Norwegian PCa population of 779 patients. The G84E allele was observed in 2.3% of patients compared to 0.7% of control individuals, OR = 3.8, P = 1 × 10-4. While there was a trend toward an earlier age at diagnosis, overall the clinicopathologic features of PCa were not significantly different in G84E carriers and non-carriers. Evaluation of 32 established common risk alleles revealed significant associations of risk alleles at 13 loci, including SNPs at 8q24, and near TET2, SLC22A3, NKX3-1, CASC8, MYC, DAP2IP, MSMB, HNF1B, PPP1R14A, and KLK2/3. When the data for each SNP are combined into a genetic risk score (GRS), Norwegian men within the top decile of GRS have over 5-fold greater risk to be diagnosed with PCa than men with GRS in the lowest decile. These results indicate that risk alleles of HOXB13 and common variant SNPs are important components of inherited PCa risk in the Norwegian population, although these factors appear to contribute little to the malignancy's aggressiveness.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Genetic factors influencing prostate cancer risk in Norwegian men

et al. 2017

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“…Genome-wide association studies (GWAS) over the last decade have identified over 100 germline single nucleotide polymorphisms (SNPs) that show significant association with relevant prostate cancer diagnosis measures, including elevated PSA, family history, and probability of future prostate cancer development [25]. In considering the predictive value of risk SNPs for evaluating men who might benefit from PSA testing, the International Consortium for Prostate Cancer Genetics (ICPCG) evaluated over 12,500 samples and established a significant relationship for 8 risk SNPs and prostate cancer [26].…”

Section: Screen Vs Not Screen: Precision Biomarkers For Risk Assementioning

confidence: 99%

Precision management of localized prostate cancer

VanderWeele

Türkbey

Sowalsky

2016

Expert Review of Precision Medicine and Drug Development

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Introduction The vast majority of men who are diagnosed with prostate cancer die of other causes, highlighting the importance of determining which patient has a risk of death from prostate cancer. Precision management of prostate cancer patients includes distinguishing which men have potentially lethal disease and employing strategies for determining which treatment modality appropriately balances the desire to achieve a durable response while preventing unnecessary overtreatment. Areas covered In this review, we highlight precision approaches to risk assessment and a context for the precision-guided application of definitive therapy. We focus on three dilemmas relevant to the diagnosis of localized prostate cancer: screening, the decision to treat, and postoperative management. Expert commentary In the last five years, numerous precision tools have emerged with potential benefit to the patient. However, to achieve optimal outcome, the decision to employ one or more of these tests must be considered in the context of prevailing conventional factors. Moreover, performance and interpretation of a molecular or imaging precision test remains practitioner-dependent. The next five years will witness increased marriage of molecular and imaging biomarkers for improved multi-modal diagnosis and discrimination of disease that is aggressive versus truly indolent.

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“…Its pilot study, performed in 100 men with a positive family history, demonstrated that screening biopsy is feasible and safe [4]. Research is preliminary; however, results of the ongoing PROFILE study are eagerly awaited.…”

mentioning

confidence: 99%

“…Research is preliminary; however, results of the ongoing PROFILE study are eagerly awaited. Its pilot study, performed in 100 men with a positive family history, demonstrated that screening biopsy is feasible and safe [4]. The main PROFILE cohort study aims to recruit 700 men, aged 40-69 years, either of Afro-Caribbean descent or with a positive family history.…”

mentioning

confidence: 99%