Clinical implications of family history of prostate cancer and genetic risk single nucleotide polymorphism (SNP) profiles in an active surveillance cohort

Abstract

Objectives To explore the potential prognostic role of family history (FH) of prostate cancer and prostate cancer risk single nucleotide polymorphisms (SNPs) in patients undergoing active surveillance (AS) for prostate cancer. This is the first study to date, which has investigated the potential prognostic role of SNP profiles in an AS cohort Patients and methods FH data were collected from patients in the Royal Marsden Hospital AS study. In all, 39 prostate cancer-risk SNPs identified from published genome wide association studies (GWAS) were genotyped using the Sequenom Platform and TaqMan™ assays from available DNA. The cumulative genetic-risk scores for each patient were then calculated using the weighted effect estimated from previous GWAS (log-additive model). FH status and the genetic-risk scores were assessed against adverse outcomes in AS, time to treatment and adverse histology on repeat biopsy, using univariable and multivariable Cox regression models to address time to treatment; and binary logistic regression to address biopsy upgrade. Results Of 471 patients, 55 (13.6%) had adverse histology on repeat biopsies and 145 (30.8%) had deferred treatment. On univariate analysis, there was no significant relationship between FH of prostate cancer in any degree of relation, and adverse histology or time to treatment. For risk score analyses, 386 patients’ DNA was studied; and there was also no relationship found between the calculated genetic risk scores and adverse histology or time to treatment (P = 0.573 and P = 0.965, respectively). The retrospective study design and the few events was the main limitation of the study. Conclusions There is currently insufficient data to support the use of FH status or prostate cancer SNP profile-risk scores as prognostic factors in AS and these should not be used to influence management decisions. As more genetic variants are discovered this may change and should be reassessed in multicentre AS cohorts.

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

“…Larger studies are required to confirm the differences observed. Little is known about the effect of FH on PrCa progression and the benefits of early diagnosis in this group [14]. All but one man diagnosed with low-risk PrCa accepted active surveillance, highlighting the growing understanding of the natural history of PrCa and the increasing acceptance of a structured monitoring strategy.…”

Novel Tools to Improve Patient Selection and Monitoring on Active Surveillance for Low-risk Prostate Cancer: A Systematic Review

“…The literature search identified 30 original articles that were included for review: 14 on magnetic resonance imaging (MRI) [8][9][10][11][12][13][14][15][16][17][18][19][20][21], 5 on serum markers [22][23][24][25][26], 5 on urinary markers [27][28][29][30][31], 4 on histopathology markers [32][33][34][35], and 2 on germline genetic markers [36,37]. Figure 1 presents the search strategy and study selection flowchart.…”

“…Goh et al studied the predictive value of 29 cancer risk-associated single nucleotide polymorphisms and family history in AS patients (n = 471) [36]. This retrospective study found no association with the intermediate end points, adverse repeat biopsy findings, and time to treatment.…”

Active Surveillance for Prostate Cancer: A Systematic Review of Clinicopathologic Variables and Biomarkers for Risk Stratification

“…On the contrary, Iremashvili and colleagues (9) aimed to identify clinical and demographic characteristics associated with an increased probability of progression and found no significant association for age, family history or baseline PSA. Several other studies also showed no relationship between family history with PSA growth (38), high grade disease (18), Gleason 4 (33), or time to treatment (39). …”