Genetics and Genomics | Open | Published:

Genetics & Genomics

Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition

British Journal of Cancer volume 118, pages 266276 (23 January 2018) | Download Citation

  • A Corrigendum to this article was published on 06 March 2018



Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA and PSAV for identifying PrCa and high-grade disease in this cohort.


PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV.


1634 participants had 3 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml−l, PSAV was not significantly associated with presence of cancer or high-grade disease. PSAV did not add to PSA for predicting time to an elevated PSA. When comparing BRCA1/2 carriers to non-carriers, we found a significant interaction between BRCA status and last PSA before biopsy (P=0.031) and BRCA2 status and PSAV (P=0.024). However, PSAV was not predictive of biopsy outcome in BRCA2 carriers.


PSA is more strongly predictive of PrCa in BRCA carriers than non-carriers. We did not find evidence that PSAV aids decision-making for BRCA carriers over absolute PSA value alone.


Men with germline mutations in BRCA2 have an increased risk of prostate cancer (PrCa), estimated at 2.5–8.6 fold increased risk for BRCA2 mutation carriers (Breast Cancer Linkage Consortium, 1999; van Asperen et al, 2005; Kote-Jarai et al, 2011). There remains debate about whether there is an increased risk of PrCa associated with BRCA1 mutations, with some studies reporting no increased risk to those reporting a 1.8–3.75 fold increased risk (Thompson et al, 2002; Leongamornlert et al, 2012; Moran et al, 2012). A number of studies have reported that BRCA2 mutation carriers have more aggressive disease, suggested by their younger age at diagnosis, higher rates of lymph node involvement and distant metastasis at diagnosis, and higher mortality rates compared with non-carriers (Tryggvadóttir et al, 2007; Mitra et al, 2008; Edwards et al, 2010; Gallagher et al, 2010; Thorne et al, 2011; Castro et al, 2013). There is increasing evidence that BRCA1 mutation carriers may also harbour more aggressive disease (Giusti et al, 2003; Gallagher et al, 2010; Castro et al, 2013). Furthermore, BRCA2-mutant localised prostate cancer demonstrates increased genomic instability and a mutational profile that more closely resembles metastastic than localised disease, therefore supporting early detection in this at risk patient population (Taylor et al, 2017).

General population prostate specific antigen (PSA) screening remains controversial due to an unclear balance of benefits, in terms of mortality reduction when compared to harms such as overdiagnosis and overtreatment. However, many expert groups continue to recommend PrCa screening with particular attention towards men with risk factors based on family history, genetics and/or race (Roobol et al, 2013; Eeles et al, 2014; Mikropoulos et al, 2014; Murphy et al, 2014).

It has previously been suggested that the rate of PSA change over time, or PSA velocity (PSAV), can be used to assist in differentiating between men with cancer from those with benign disease (Carter et al, 1992; Berger et al, 2005). Monitoring PSA over time could also improve the sensitivity of screening. It is also possible that PSAV could distinguish between men who might have advanced or aggressive disease that would require definitive treatment thus avoiding overdiagnosis and overtreatment (Carter et al, 2006; Carter et al, 2007).

However, the utility of PSAV in PrCa decision-making has been called into question. In particular, while PSAV may be predictive of biopsy outcome in univariate analyses, it has not been shown to improve the predictiveness of biopsy outcome over the absolute value of PSA (Roobol et al, 2004; Vickers et al, 2011; Loughlin, 2014). Although some studies have suggested that PSAV can be used to identify men with aggressive disease, these did not investigate whether calculation of PSAV provided additional information than the most recent PSA value (Carter et al, 1992; D'Amico et al, 2004; D'Amico et al, 2005). PSA and PSAV are highly correlated, and this may explain why PSAV does not add predictive value (Vickers et al, 2011). As a result of these considerations, PSAV has been removed from all major guidelines concerning the detection of prostate cancer.

It is currently unknown whether PSAV provides more information, beyond PSA absolute value, among a cohort of men considered to be at increased genetic risk of PrCa and aggressive disease. The IMPACT study (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in men at higher genetic risk and controls; is an international multi-centre study evaluating the role of targeted PSA screening in men with a BRCA1 or BRCA2 mutation and was established in 2005 (Bancroft et al, 2014). To date, 3000 men have been recruited from 20 countries across the world. Men are followed up with annual (or biannual in the Dutch cohort) PSA screening for a minimum of 5 years within the study and this has produced a wealth of PSA results and follow-up data over time. The primary end-point of the IMPACT study is to determine the incidence, stage and pathology of screen-detected prostate cancer in the study population; a secondary end-point is to determine a profile of PSA level and its predictive value for the development of prostate cancer in the study population. The objective of the present study was to determine whether PSA values and/or PSAV were associated with PrCa and aggressive tumours among men at increased risk enrolled in the IMPACT trial.

Materials and methods

Patient selection

The design and eligibility criteria for the IMPACT study have been described elsewhere (Mitra et al, 2008; Bancroft et al, 2014). The protocol was approved by the West-Midlands Research and Ethics Committee in the UK (reference 05/MRE07/25), and subsequently by each participating institution’s local committee. Briefly, men aged between 40 and 69 were recruited from families with a known pathogenic germline BRCA1 or BRCA2 mutation. Men were invited to enrol if they had tested positive (carriers) or negative for the familial mutation (BRCA1/2 non-carriers), or if they were at 50% risk of inheriting a mutation but had not yet undergone predictive genetic testing. All participants provide written consent. Men with PrCa or with a prior diagnosis of another cancer with a prognosis of <5 years were excluded. In the Dutch centres, men were also excluded if they had PSA screening prior to study entry.

According to the IMPACT study design, men underwent annual PSA screening and those with a PSA >3.0 ng ml−l were referred for a 10- or 12-core transrectal ultrasound guided (TRUS) biopsy based on institutional clinic practices. Men with a PSA >3.0 ng/ml and a negative biopsy continue annual screening, with a repeat biopsy recommended when PSA increased by >50%. Men were also referred for biopsy if they had a PSA 3.0 ng ml−l but clinical suspicion (e.g., abnormal digital rectal examination or clinical symptoms). After 5 years in the study, men at a subset of centres were also offered an elective biopsy.

PSA readings in the study are validated in a central laboratory to exclude inter-site variations. The results found a Spearman’s agreement of 0.95 between study sites (Bancroft et al, 2014).

Statistical considerations

PSA velocity (PSAV) has been used as a marker to inform decisions about biopsy or about the timing of the next PSA screen. With respect to the former, we considered that a physician had the most recent PSA measurements available. Our study question was therefore whether adding PSAV to this data point improves prediction of presence of PrCa at biopsy. As elevated PSA is the primary indication in routine clinical practice, our main analysis was restricted to men who had any PSA 3.0 ng ml−l prior to biopsy. A sensitivity analysis was conducted including all men who underwent biopsy. We created logistic regression models, adjusted for last PSA measurement and age, for the outcomes of any grade and high-grade cancer. PSAV was calculated using three methods: arithmetic equation of change in PSA over time; linear regression; rate of PSA change using first and last values only. We also used cubic splines with knots at the tertiles to test for non-linearity in PSA and in PSAV.

To investigate whether the effect of PSAV on predicting biopsy outcome differed based on BRCA status, we included an interaction term between PSAV and BRCA status (BRCA1 or BRCA2 carriers vs BRCA non-carrier patients, and BRCA2 carriers vs BRCA1 and BRCA non-carrier patients). Due to a limited number of events, this analysis was performed only for the outcome of any cancer on biopsy. This analysis included 13 cancers diagnosed among 55 BRCA1 carriers and 23 cancers among 65 BRCA2 carriers.

To determine whether PSAV could aid decisions about screening frequency, e.g., whether a man with a high PSAV should receive a subsequent PSA test at a shorter interval than a man with low PSAV, we assessed whether PSAV was associated with having a future PSA >3.0 ng ml−l. As a minimum of three PSA measurements are required for accurate estimation of PSAV, we created Cox proportional hazards models for the time from the first PSA measurement to the patient’s third PSA measurement >3.0 ng ml−l. Four models were then created: one including the third PSA measurement only, and the others including both the third PSA measurement and each of the three methodologies for calculating PSAV. Men who had a PSA >3.0 ng ml−l within the first three PSA measurements were excluded from this analysis. A total of 1086 men were included.

We planned to first evaluate the independent statistical significance of PSAV in models that also included absolute PSA level. If significant, we planned to estimate the improvement in concordance index afforded by PSAV after 10-fold cross-validation. All analyses were conducted using Stata 13.0 (Stata Corp., College Station, TX, USA).


Of the 2942 men recruited to the IMPACT study, 1654 men had three or more PSA measurements and appropriate clinical follow-up to be included in the analyses (Figure 1). Table 1 shows the demographic, PSA and biopsy grade characteristics of the analysis cohorts. The cohort of 1654 men consisted of 510 BRCA1 mutation carriers, 584 BRCA2 mutation carriers, 260 BRCA1 non-carriers and 288 BRCA2 non-carriers. Two men carried both a BRCA1 and BRCA2 mutation (included in the BRCA2 group for genetic sub-analysis) and 10 had not yet had a predictive test for the BRCA mutation in their family (excluded from genetic sub-analysis). In this cohort, 174 men underwent prostate biopsy, with 45 men having any grade cancer of whom 21 having Gleason score 7 or higher (high-grade) cancer. Among men who had any PSA >3.0 ng ml−l, 40 had any grade of whom 20 had high-grade cancer.

Figure 1
Figure 1

Consort diagram of study population. The two bolded cohorts were included for in-depth analysis, as they had 3 or more PSA values available for analysis and underwent a prostate biopsy.

Table 1: Patient characteristics

The median age at the first PSA of BRCA2 carriers was significantly younger than both BRCA1 carriers and non-carriers (51 vs 53 vs 54 years, respectively, P<0.0001). Overall, BRCA2 and BRCA1 carriers had significantly lower first PSA values than non-carriers (0.80 vs 0.80 vs 0.89 ng ml−l; P=0.022; however, overall there was no statistically significant difference in the median PSAV between the BRCA2, BRCA1 and non-carrier groups (P=0.8).

The median age at first PSA reading of men diagnosed with cancer was higher than that of men without cancer (60 vs 53 years, U=22069, z=−5.24, P<0.001). The median most recent PSA (i.e., PSA at diagnosis for cancer cases) was significantly higher for those with cancer compared with those without cancer (3.70 vs 0.90 ng ml−l) U=8564, z=−9.34, P<0.001). The median PSAV was significantly higher for those with cancer vs those without cancer (medians: 0.56 vs 0.02 ng/ml/yr, U=9641, z=−9.012, P<0.001). Of those diagnosed with cancer, there was no significant difference between the proportion of BRCA2 carriers with a PSAV (calculated by linear regression) >0.35 ng ml−l per year compared with BRCA1 carriers and non-carrier controls (78.3 vs 61.5 vs 53.8%, p0.28).

We next assessed whether adding PSAV to the most recent PSA measurement would improve the ability to determine which men should undergo biopsy. Using cubic splines, we investigated and found no evidence of non-linearity in PSA or in PSAV. Among men with any PSA measurements >3.0 ng/ml, PSAV was not significantly associated with either any grade or high-grade cancer after adjusting for most recent PSA measurement (Table 2). We repeated these analyses including all men who were biopsied, and found that PSAV was not statistically significant in any of the models (Table 3).

Table 2: Models for any grade and high-grade cancers among men with any PSA measurement 3.0 ng/ml, N=116
Table 3: Models for any grade and high grade cancers among all men undergoing biopsy, N=174

Additionally, we assessed whether PSAV affected the prediction of PrCa at biopsy differently based on BRCA status. When comparing BRCA1 and BRCA2 carriers to BRCA1/2 non-carriers, we found a significant interaction between BRCA status and the last PSA before biopsy (P=0.031), however there was no evidence of an interaction between BRCA status and PSAV (Table 4). However, when comparing BRCA2 carriers to BRCA1 carriers and BRCA1/2 non-carriers, we found evidence of interactions between BRCA2 status and last PSA before biopsy (P=0.078) and significant interactions between BRCA2 status and PSAV calculated using the arithmetic equation and linear regression (P=0.024 and P=0.049 respectively, Table 4).

Table 4: Models for any grade cancer based on BRCA status (BRCA positive carriers vs BRCA negative non-carriers) and BRCA2 status (BRCA2 positive vs BRCA1 positive and BRCA negative)

Based on these interactions, we performed subgroup analyses by BRCA2 status. All models were adjusted for age at biopsy and last PSA before biopsy. Due to a limited number of events (26 cancers in BRCA2 non-carriers and 23 in BRCA2 carriers), these models were somewhat overfit. No evidence of an association between PSA and any grade cancer or PSAV and any grade cancer was seen in BRCA2 carriers or non-carriers, likely due to the strong correlation between PSA and PSAV (Table 5).

Table 5: Models for any grade cancer by BRCA2 status (BRCA2 carriers vs BRCA1 carriers and BRCA1/2 non-carriers)

We then investigated whether PSAV was associated with time to PSA 3.0 ng ml−l. Using Cox proportional hazards models, we found no evidence of an association between PSAV and time from the third PSA measurement to PSA 3.0 ng ml−l. Out of 1533 men who did not have a PSA 3.0 ng ml−l within the first three PSA tests, there were 28 who had a PSA 3.0 ng ml−l within 1 year, 50 within 2 years and 62 within 3 years.


This is the first study to show that there are differences in PSA values among men with different genetic backgrounds. These PSA differences could be used to identify those men considered to be at high genetic risk of more aggressive disease. However, when evaluated with absolute PSA values, PSAV did not appear to provide additional information for BRCA1 or BRCA2 carriers.

A major problem of PSA screening is that, in attempting to detect clinically significant disease, it is inevitable that indolent disease will also be detected leading to overdiagnosis. However, early diagnosis and identification of men with high-risk disease is important to prevent mortality from PrCa. This might be particularly essential in light of recent publications indicating that men with a BRCA1 or BRCA2 mutation are at risk of more aggressive disease (Castro et al, 2013; Castro et al, 2015), early identification of those with clinically significant disease will be imperative. In view of the controversy about the role of PSAV in prostate screening in the general population, it was important to assess its role in BRCA1 and BRCA2 carriers and whether it added to the ability to detect clinically significant disease.

In this analysis of the IMPACT study cohort, we found BRCA2 carriers on average to be screened at a relatively young age. This may account for lower overall PSA values for BRCA2 carriers in this analysis compared to non-carrier controls. However, there were no differences in median PSAV between carriers and non-carriers. Given the possibility that higher PSAV may associate with aggressive PrCa (D'Amico et al, 2004; D'Amico et al, 2005), we would expect BRCA2 carriers who are at risk of aggressive disease would exhibit higher PSAVs (Castro et al, 2013; Castro et al, 2015). BRCA2 carriers in this group may be too young to demonstrate this trend at this point of follow up.

A single PSA reading over 3 ng ml−l was applied to guide biopsy decisions according to the IMPACT protocol, as well as if there was clinical suspicion on digital rectal examination or clinical symptoms. PSAV was not a good indicator in this analysis for distinguishing between those with any grade cancer and high-grade cancer when men were biopsied for either indication. It is possible that PSAV could be a good predictor of high-grade disease in men who had PSA values 2 ng ml−l (Kitagawa et al, 2014). However, due to the protocol’s 3 ng/ml PSA threshold for prostate biopsy, we were limited in the number of cancers diagnosed when PSA was 2 ng ml−l. Further follow up will be required to assess when additional cancers are diagnosed. As part of the IMPACT trial, there is an optional end of study biopsy regardless of PSA. This may help delineate PSAV among men diagnosed with PrCa with low PSA values (Carter et al, 1992; Kitagawa et al, 2014).

A strength of this study is the unique patient cohort of men with a genetic predisposition to PrCa, in particular BRCA2 carriers who are predisposed to aggressive PrCas (Mitra et al, 2008; Narod et al, 2008; Castro et al, 2013; Castro et al, 2015). Within the group of BRCA2 carriers, PSAV proved predictive of any grade cancer, however, given the low number of cancers diagnosed overall it was not possible to assess whether PSAV was associated with high grade cancer and BRCA2 status. A high PSAV in an individual with a BRCA2 mutation could be used as an indicator of presence of PrCa and therefore as an indication for prostate biopsy. This model could lead to diagnosis of lower grade cancers in BRCA2 carriers. It may lead to better prognosis for men at risk for more aggressive disease and better disease-free survival when treated early. Although there are no definitive treatment recommendations for men with BRCA2 mutations when found to be diagnosed with low grade cancers, their risk for aggressive disease may spur them to follow a more active treatment plan such as radical prostatectomy vs external-beam radiation therapy or active surveillance (Bratt and Loman, 2015; Castro et al, 2015).

One major limitation of this analysis is the relatively small number of men in the study who had undergone diagnostic prostate biopsy. End of study biopsies are not mandated and the true incidence of PrCa is unknown in this population. As more men progress through the IMPACT screening study, undergo prostate biopsy and follow-up time increases, the findings from this analysis can be explored and validated. At this point, the results from this analysis did not justify modifying the study algorithm to include a PSAV calculation.

In the general population, PSAV is not part of any major screening guideline. We also did not find PSAV to be an independent prognostic factor in BRCA1 or BRCA2 mutation carriers and therefore for screening an absolute PSA cut-off value should preferably be used.


PSA is more strongly predictive of PrCa in BRCA carriers than BRCA non-carriers. We did not find evidence that PSAV aids to decision making for either indicating biopsy or frequency of follow-up testing in BRCA carriers, but further follow-up is required for more definitive conclusions.


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We are indebted to all of the men who are taking part in this study. This research is coordinated by the Institute of Cancer Research, London, UK and is supported by grants from Cancer Research UK (Grant references (C5047/A21332, C5047/A13232 and C5047/A17528) and The Ronald and Rita McAulay Foundation. Mr and Mrs Jack Baker for the study in NorthShore University HealthSystem, Evanston, Illinois and Myriad Genetics Laboratory, Salt Lake City, Utah, for providing research BRCA testing rates for NorthShore University HealthSystem participants. We acknowledge funding from the NIHR to the Biomedical Research Center at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, at Central Manchester Foundation Trust and the Oxford Biomedical Research Centre Program. We acknowledge that in Australia, this project was co-funded by Cancer Council Tasmania and Cancer Australia, grant number 1006349 (2011–2013), Prostate Cancer Foundation of Australia, grant number PCFA PRO4 (2008) and Cancer Councils of Victoria and South Australia, grant number 400048 (2006–2008), The Victorian Cancer Agency Clinical Trial Capacity CTCB08_14, Cancer Australia & Prostate Cancer Foundation of Australia (2014–2016) grant number 1059423, and Translational grants EOI09_50. The Association of International Cancer Research funded data collection in The Netherlands (AICR 10–0596). We acknowledge funding from the Basser Center for BRCA (to S Domchek). We acknowledge funding from the National Cancer Institute [P30-CA008748], the Sidney Kimmel Center for Prostate and Urologic Cancers, and David H. Koch through the Prostate Cancer Foundation, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre Program in UK, Swedish Cancer Society (Cancerfonden project no. 11–0624), and the Swedish Research Council (VR-MH project no. 2016–02974). We acknowledge funding from the Slovenian Research Agency, Research programme P3–0352. Elena Castro acknolwedges funding from a Juan de la Cierva’ fellowship from MINIECO (grant reference IJCI- 2014–19129). We acknowledge the support of the Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III (organismo adscrito al Ministerio de Economía y Competitividad) and ‘Fondo Europeo de Desarrollo Regional (FEDER), una manera de hacer Europa’ (PI10/01422, PI13/00285, PIE13/00022, PI16/00563 and CIBERONC) and the Institut Català de la Salut and Autonomous Government of Catalonia (2009SGR290, 2014SGR338 and PERIS Project MedPerCan). We acknowledge David Fisas, Consol Lopez and Dr Nuria Calvo for their involvement in the project at Hospital de Sant Pau, Barcelona. We are grateful to the members of the Data and Safety Monitoring Committee: S. Duffy (Chair), P. White (UK NEQAS representative) and J. McGrath (BAUS representative). We acknowledge the contribution of past members of the IMPACT Steering Committee: J. Melia, S. Moss, P. Wilson and G. Mitchell.

Author information


  1. The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK

    • Christos Mikropoulos
    • , Sibel Saya
    • , Elizabeth Bancroft
    • , Tokhir Dadaev
    • , Elizabeth Page
    • , Alexander Dias
    • , Daniel A Leongamornlert
    • , Anthony Chamberlain
    • , Jenny Pope
    • , David Dearnaley
    • , Clare Moynihan
    • , Zsofia Kote-Jarai
    •  & Rosalind A Eeles
  2. The John and Carol Walter Center for Urological Health, Department of Surgery, North Shore University Health System, Evanston, IL 60201, USA

    • Christina G Hutten Selkirk
    • , Charles Brendler
    •  & Brian T Helfand
  3. Center for Medical Genetics, Department of Medicine, NorthShore University HealthSystem, Evanston, IL 60201, USA

    • Christina G Hutten Selkirk
    •  & Anna C Newlin
  4. Royal Marsden NHS Foundation Trust, Fulham Rd, London SW3 6JJ, UK

    • Elizabeth Bancroft
    • , Alexander Dias
    • , Audrey Ardern-Jones
    • , David Dearnaley
    • , Vincent Khoo
    •  & Rosalind A Eeles
  5. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA

    • Emily Vertosick
    •  & Andrew Vickers
  6. Genomic Medicine, Manchester Academic Health Sciences Centre, Division of Evolution and Genomic Sciences, University of Manchester, Central Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL, UK

    • D Gareth Evans
    • , Jeanette Rothwell
    •  & Karen Tricker
  7. Department of Medical Genetics, Oslo University Hospital, Oslo 0372, Norway

    • Lovise Maehle
    •  & Eli Marie Grindedal
  8. Akershus University Hospital, Lørenskog 1478, Norway

    • Karol Axcrona
  9. Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre, East Melbourne, VIC 3000, Australia

    • Kate Richardson
    • , Paul A James
    •  & Joanne McKinley
  10. The Sir Peter MacCallum Department of Oncology, University of Melbourne, VIC 3010, Australia

    • Kate Richardson
    • , Paul A James
    •  & Declan Murphy
  11. Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton SO16 5YA, UK

    • Diana Eccles
  12. Cancer Sciences, Faculty of Medicine, University of Southampton, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK

    • Diana Eccles
  13. Department of Clinical Genetics, Vejle Hospital, Vejle 7100, Denmark

    • Thomas Jensen
    •  & Palle J Osther
  14. Leiden University Medical Center, Department of Clinical Genetics, Leiden, ZA 2333, The Netherlands

    • Christi J van Asperen
  15. Netherlands Foundation for the Detection of Hereditary Tumors, Leiden, ZA 2333, The Netherlands

    • Hans Vasen
    • , Janneke Ringelberg
    •  & Wendy A van Zelst-Stams
  16. Radboud University Medical Center, Nijmegen, GA 6525, The Netherlands

    • Lambertus A Kiemeney
    • , Ruben Cremers
    •  & Gerald Verhaegh
  17. International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin 70-204, Poland

    • Cezary Cybulski
    • , Dominika Wokolorczyk
    •  & Jan Lubinski
  18. Clinical Genetics Unit, Birmingham Women's Hospital, Birmingham B15 2TG, UK

    • Rachel Hart
    •  & Wayne Glover
  19. Department of Urology, Repatriation General Hospital, Daw Park, SA 5041, Australia

    • Jimmy Lam
    •  & Louise Taylor
  20. Hereditary Cancer Program, Catalan Institute of Oncology (ICO-IDIBELL, CIBERONC), L’Hospitalet de Llobregat, Barcelona 08908, Spain

    • Monica Salinas
    •  & Lidia Feliubadaló
  21. Department of Clinical Genetics, Erasmus Medical Center, Rotterdam 3015 CE, The Netherlands

    • Rogier Oldenburg
    •  & Chris Bangma
  22. Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen 9713 GZ, The Netherlands

    • Jan C Oosterwijk
  23. Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield S10 2TH, UK

    • Jackie Cook
  24. Royal Hallamshire Hospital, Sheffield S10 2JF, UK

    • Derek J Rosario
  25. Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT 84103, USA

    • Saundra S Buys
    •  & Tom Conner
  26. Basser Research Center, University of Pennsylvania, Philadelphia, PA 19104, USA

    • Susan Domchek
    •  & Jacquelyn Powers
  27. Department of Genetics, University Medical Centre Utrecht, Utrecht, CX, The Netherlands

    • Margreet GEM Ausems
  28. Genetics Department and Research Center, Portuguese Oncology Institute, Porto 4200-072, Portugal

    • Manuel R Teixeira
    •  & Sofia Maia
  29. Biomedical Sciences Institute (ICBAS), Porto University, Porto 4200-072, Portugal

    • Manuel R Teixeira
  30. South East Thames Genetics Service, Guy’s Hospital, London SE1 9RT, UK

    • Louise Izatt
  31. Center of Familial Breast and Ovarian Cancer, University Hospital of Cologne, Cologne 50937, Germany

    • Rita Schmutzler
    •  & Kerstin Rhiem
  32. McGill Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, QC H3A 0G4, Canada

    • William D Foulkes
    •  & Talia Boshari
  33. Duncan Guthrie Institute of Medical Genetics, Yorkhill NHS Trust, Glasgow G38SJ, UK

    • Rosemarie Davidson
  34. The Netherlands Cancer Institute, Amsterdam 1066 CX, The Netherlands

    • Marielle Ruijs
    •  & Neil Aaronson
  35. Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, HX 6229, The Netherlands

    • Apollonia TJM Helderman-van den Enden
  36. Hereditary Cancer Clinic, Prince of Wales Hospital, Randwick, NSW 2031, Australia

    • Lesley Andrews
  37. Churchill Hospital, Headington, Oxford OX3 7LE, UK

    • Lisa Walker
    •  & Freddie C Hamdy
  38. St George’s Hospital, Tooting, London SW17 0QT, UK

    • Katie Snape
  39. Northern Genetics Service, Newcastle upon Tyne Hospitals, Newcastle NE1 3BZ, UK

    • Alex Henderson
    •  & Irene Jobson
  40. Parkville Familial Cancer Centre, The Royal Melbourne Hospital, Grattan St, Parkville, VIC 3050, Australia

    • Geoffrey J Lindeman
    •  & Kylie Shackleton
  41. Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3050, Australia

    • Geoffrey J Lindeman
  42. Department of Medicine, The University of Melbourne, Parkville, VIC 3050, Australia

    • Geoffrey J Lindeman
  43. Karolinska University Hospital and Karolinska Institutet, Solna 171 77, Sweden

    • Annelie Liljegren
  44. Familial Cancer Centre, Monash Health, Clayton, VIC 3168, Australia

    • Marion Harris
  45. VU University Medical Center, Amsterdam 1081 HV, The Netherlands

    • Muriel A Adank
  46. Familial Cancer Service, Westmead Hospital, Westmead, Sydney, NSW 2145, Australia

    • Judy Kirk
  47. Centre for Cancer Research, The Westmead Institute for Medical Research, Westmead, Sydney, NSW 2155, Australia

    • Judy Kirk
  48. Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK

    • Amy Taylor
  49. Genetic Health Queensland, Royal Brisbane & Women's Hospital, Herston, QLD 4029, Australia

    • Rachel Susman
  50. The Genetic Institute, Kaplan Medical Center, Rehovot 76100, Israel

    • Rakefet Chen-Shtoyerman
  51. Genetic Services of WA, King Edward Memorial Hospital, Subiaco, WA 6008, Australia

    • Nicholas Pachter
  52. School of Medicine and Pharmacology, University of Western Australia, Perth, WA 6009, Australia

    • Nicholas Pachter
  53. Hunter Family Cancer Service, Waratah, NSW 2298, Australia

    • Allan Spigelman
  54. University of New South Wales, St Vincent’s Clinical School, NSW 2052, Australia

    • Allan Spigelman
  55. The Kinghorn Cancer Centre, St Vincent's Hospital, Sydney, NSW 2010, Australia

    • Allan Spigelman
  56. NE Thames Regional Genetics Service, Great Ormond St Hospital & UCL Institute of Women’s Health, London WC1N 3JH, UK

    • Lucy Side
  57. Institute of Oncology, Ljubljana 1000, Slovenia

    • Janez Zgajnar
  58. Hospital de Sant Pau, Barcelona 08041, Spain

    • Josefina Mora
  59. Peninsular Genetics, Derriford Hospital, Plymouth PL6 8DH, UK

    • Carole Brewer
  60. Royal Devon and Exeter Hospital, Exeter EX2 5DW, UK

    • Carole Brewer
    •  & John McGrath
  61. High Risk and Cancer Prevention Clinic, Vall d'Hebron University Hospital, Barcelona 08035, Spain

    • Neus Gadea
  62. North West Thames Regional Genetics Service, London North West Healthcare NHS Trust, London HA1 3UJ, UK

    • Angela F Brady
  63. St James’ Hospital, Dublin 8, Ireland

    • David Gallagher
  64. Academic Medical Center, Amsterdam 1105 AZ, The Netherlands

    • Theo van Os
  65. St Michael’s Hospital, Bristol BS2 8EG, UK

    • Alan Donaldson
  66. Landspitali—the National University Hospital of Iceland, Reykjavik 101, Iceland

    • Vigdis Stefansdottir
    •  & Oskar Johannsson
  67. University of Leicester, Leicester LE1 7RH, UK

    • Julian Barwell
  68. University Hospitals Leicester, Leicester LE1 5WW, UK

    • Julian Barwell
  69. Genetic Medicine, Royal Melbourne Hospital, Melbourne, VIC 3050, Australia

    • Paul A James
  70. Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel

    • Eitan Friedman
  71. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel

    • Eitan Friedman
  72. Istituto Nazionale dei Tumori, Milano 20133, Italy

    • Nicola Nicolai
  73. Cheshire and Mersey Clinical Genetics Service, Liverpool Women’s Hospital, Liverpool L8 7SS, UK

    • Lynn Greenhalgh
  74. Fox Chase Cancer Center, Philadelphia, PA 19111, USA

    • Elias Obeid
  75. Tata Memorial Centre, Mumbai, Maharashtra 400012, India

    • Vedang Murthy
  76. National Cancer Institute, Bratislava 83310, Slovak Republic

    • Lucia Copakova
  77. Cancer Research Initiatives Foundation, Subang Jaya Medical Centre, Subang Jaya, Selangor 47500, Darul Ehsan, Malaysia

    • Soo-Hwang Teo
  78. The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA

    • Sara Strom
  79. Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden 01069, Germany

    • Karin Kast
  80. National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden 01307, Germany

    • Karin Kast
  81. German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg 69120, Germany

    • Karin Kast
  82. Prostate Cancer Unit, Spanish National Cancer Research Centre, Madrid 28029, Spain

    • Elena Castro
  83. Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik 101, Iceland

    • Jorunn Eyfjord
  84. Imperial College Healthcare NHS Trust, London, London W2 1NY, UK

    • Alison Falconer
  85. HCA Healthcare Laboratories, London WC1E 6JA, UK

    • Christopher S Foster
  86. University Hospital, Umea 907 37, Sweden

    • Henrik Gronberg
  87. Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX1 2JD, UK

    • Freddie C Hamdy
    •  & Hans Lilja
  88. University College London Hospitals NHS Foundation Trust, London NW1 2BU, UK

    • Anita V Mitra
  89. CHS National Cancer Control Center, Carmel Medical Center, Haifa 3436212, Israel

    • Gad Rennert
  90. Nottingham City Hospital, Nottingham NG5 1PB, UK

    • Mohnish Suri
  91. The IMPACT Study Collaborators List see Appendix 1

  92. Centre for Cancer Prevention, Queen Mary University of London, London EC1M 6BQ

    • Sue Moss
  93. Departments of Laboratory Medicine, Surgery, and Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA

    • Hans Lilja
  94. Department of Translational Medicine, Lund University, Malmö 205 02, Sweden


  1. The IMPACT study collaborators

    1. The IMPACT Study Collaborators List see Appendix 1


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Competing interests

Hans Lilja holds patents for free PSA, hK2, and intact PSA assays, and is named, along with Andrew J. Vickers, on a patent application for a statistical method to detect prostate cancer. The marker assay patents and the patent application for the statistical model has been licensed and commercialised as the 4Kscore by OPKO Diagnostics. Drs Vickers and Lilja receive royalties from sales of this test. Additionally, Dr Lilja owns stock and Dr Vickers owns stock options in OPKO. Professor Rosalind Eeles—Janssen: provided medical education support to GU ASCO Feb 2013. Succinct Communications: received an honorarium and expenses for attending and speaking at UK Cancer Convention Oct 2013. The authors have no other conflict of interest to declare.

Corresponding author

Correspondence to Rosalind A Eeles.


Appendix 1

The IMPACT Collaborators

IMPACT Study Steering Committee

Rosalind Eeles—Institute of Cancer Research, London

Elizabeth Bancroft—Royal Marsden NHS Foundation Trust, London

Elizabeth Page—Institute of Cancer Research, London

Zsofia Kote-Jarai—Institute of Cancer Research, London

Audrey Ardern-Jones—Royal Marsden NHS Foundation Trust, London

Chris Bangma—Erasmus University Medical Center, Rotterdam

Elena Castro—CNIO, Madrid

David Dearnaley—Institute of Cancer Research, London

Alison Falconer—Imperial College Healthcare NHS Trust, London, UK

Christopher Foster—HCA Pathology Laboratories, London

Henrik Grönberg—University Hospital, Umea

Freddie C. Hamdy—University of Oxford, Oxford

Óskar Þór Jóhannsson—Landspitali—National University Hospital of Iceland, Reykjavik

Vincent Khoo—Royal Marsden NHS Foundation Trust, London

Diana Eccles—Wessex Clinical Genetics Service, Southampton

Hans Lilja—MSKCC, New York & University of Oxford, Oxford

Gareth Evans—St Mary’s Hospital, Manchester, UK

Jorunn Eyfjord—University of Iceland, Reykjavik

Jan Lubinski—International Hereditary Cancer Center, Szczecin

Lovise Maehle—Norwegian Radium Hospital, Oslo

Christos Mikropoulos—The Institute of Cancer Research

Alan Millner—Royal Marsden NHS Foundation Trust, London

Geoffrey Lindeman—Royal Melbourne Hospital; WEHI; Uni of Melbourne, Melbourne

Anita Mitra—University College London Hospitals, London

Sue Moss—Queen Mary University of London

Clare Moynihan—Institute of Cancer Research, London

Gad Rennert—CHS National Cancer Control Center, Carmel Medical Center, Haifa

Mohnish Suri—Nottingham City Hospital, Nottingham, UK

Penny Wilson—Director, BioZenix, Cheshire

Rosalind Eeles, Elizabeth Bancroft, Elizabeth Page, Sibel Saya, Alex Dias, Natalie Taylor, Kathryn Myhill, Sarah Thomas, Ashton Stroud, Jenny Pope, Anthony Chamberlain, Diana Keating—Coordinating Centre, Institute of Cancer Research, London

Australia (*more than 1 affiliation)

Gillian Mitchell*, Sue Shanley, Kate Richardson, Joanne McKinley, Lara Petelin, Morgan Murphy, Lyon Mascarenhas, Paul James*—Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre, East Melbourne, VIC

Gillian Mitchell*, Paul James*—The Sir Peter MacCallum Department of Oncology, University of Melbourne, VIC

Paul James*—Genetics Medicine, Royal Melbourne Hospital, Melbourne, VIC

Declan Murphy—Department of Urology, Peter MacCallum Cancer Centre, East Melbourne, VIC

Jimmy Lam, Louise Taylor, Cathy Miller, Alan Stapleton, Michael Chong—Department of Urology, Repatriation General Hospital, Daw Park, SA

Graeme Suthers, Nicola Poplawski—SA Clinical Genetics Service, SA Pathology (at Women's & Children's Hospital), North Adelaide, SA

Katherine Tucker*, Lesley Andrews, Jessica Duffy—Hereditary Cancer Clinic, Prince of Wales Hospital, Randwick, NSW

Richard Millard—Department of Urology, Prince of Wales Hospital, Randwick, NSW

Robyn Ward, Rachel Williams—Hereditary Cancer Clinic, Prince of Wales Clinical School, Faculty of Medicine, UNSW, Sydney, NSW

Phillip Stricker—St Vincent's Clinic, Sydney, NSW

Judy Kirk*, Michelle Bowman—Familial Cancer Service, Westmead Hospital, Wentworthville, NSW

Judy Kirk*—Centre for Cancer Research, The Westmead Institute for Medical Research, NSW

Manish Patel—Westmead Hospital, Wentworthville, NSW

Marion Harris, Shona O'Connell, Clare Hunt, Courtney Smyth—Familial Cancer Centre, Monash Health, Clayton, VIC

Mark Frydenberg—Monash Medical Centre, VIC

Geoffrey Lindeman*, Kylie Shackleton, Catherine Morton—Parkville Familial Cancer Centre, The Royal Melbourne Hospital, Grattan St, Parkville, VIC

Geoffrey Lindeman*—Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC

Geoffrey Lindeman*—Department of Medicine, The University of Melbourne, Parkville, VIC

Rachel Susman, Julie McGaughran, Melanie Boon—Genetic Health Queensland, Royal Brisbane & Women's Hospital, Herston, QLD

Nicholas Pachter*, Sharron Townshend, Lyn Schofield, Cassandra Nicholls—Genetic Services of WA, King Edward Memorial Hospital, Subiaco, WA

Nicholas Pachter*—Department of Paediatrics, University of Western Australia, Perth, WA

Allan Spigelman*, Margaret Gleeson—Hunter Family Cancer Service, Waratah, NSW

Allan Spigelman*—University of New South Wales, St Vincent’s Clinical School, NSW

Allan Spigelman*—Hereditary Cancer Clinic, The Kinghorn Cancer Centre, St Vincent's Hospital, Sydney, NSW

David Amor*, Jo Burke, Briony Patterson—Tasmanian Clinical Genetics Service, Hobart, TAS

David Amor*—Murdoch Childrens Research Institute, Parkville, VIC

Peter Swindle—Mater Private Hospitals, QLD

Rodney Scott—School of Biomedical Sciences and Pharmacy, University of Newcastle, NSW

Victorian Cancer Biobank, Carlton, VIC

Department Gynaecological Oncology Laboratory, Westmead Hospital, Centre for Cancer Research, NSW

PathWest (Clinical Trials Lab), Nedlands, WA

Pathology Queensland (Central Laboratory; Health Support Queensland), QLD Department of Health, Herston, QLD


William Foulkes, Talia Boshari, Armen Aprikian—McGill University, Montreal


Thomas Jensen, Anders Bojeson, Palle Osther, Anne-Bine Skytte, Dorthe Cruger, Majbritt Kure Tøndering—Vejle Hospital, Vejle

Anne-Marie Gerdes—Odense University Hospital, Odense


Rita Schmutzler, Kerstin Rhiem, Petra Wihler—Center of Familial Breast and Ovarian Cancer, University Hospital of Cologne, Cologne

K Kast, C Griebsch—University Hospital Dresden


Oskar Johannsson, Vigdis Stefansdottir—University Hospital of Iceland, Reykjavik


Vedang Murthy, Rajiv Sarin, Kasturi Awatagiri, Sujata Ghonge, Pradnya Kowtal, Gouri Mulgund—Tata Memorial Centre, Mumbai


David Gallagher, Richard Bambury, Michael Farrell, Fergal Gallagher, Ingrid Kiernan—Mater Private Hospital, Dublin


Eitan Friedman—Chaim Sheba Medical Center, Tel-Hashomer and the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv

Rakefet Chen-Shtoyerman, Alon Basevitch, Dan Leibovici, Ehud Melzer and Sagi Josefsberg Ben-Yehoshua—The Genetic Institute, the Gastroenterology Institute and the Urology Department, Kaplan Medical Centre, Rehovot


Nicola Nicolai, Paolo Radice, Riccardo Valdagni, Tiziana Magnani, Simona Gay—Istituto Nazionale dei Tumori, Milan


Soo Hwang Teo, Hui Meng Tan, Sook-Yee Yoon—Cancer Research Initiatives Foundation, Subang Jaya Medical Centre, Selangor Darul Ehsan

Soo Hwang Teo, Meow Keong Thong—University of Malaya, Kuala Lumpur

The Netherlands

STOET—Stichting Opsporing Erfelijke Tumoren, Leiden

Christi van Asperen—Leiden University Medical Centre, Leiden

Bart Kiemeney. Wendy van Zelst-Stams—Radboud University Nijmegen Medical Centre

Margreet G.E.M. Ausems, Rob B. Van der Luijt—University Medical Center Utrecht

Theo van Os—Academic Medical Center, Amsterdam

Mariëlle W.G. Ruijs—Netherlands Cancer Institute, Amsterdam

Muriel A. Adank—VU University Medical Center, Amsterdam

Rogier A. Oldenburg—Erasmus Medical Center, Rotterdam

A. (Paula) T.J.M. Helderman- van den Enden, B.A.H. Caanen—University Hospital Maastricht

Jan C. Oosterwijk—University Medical Centre Groningen


Lovise Maehle, Pal Moller, Bjorn Brennhovd, Heidi Medvik, Eldbjørg Hanslien—Norwegian Radium Hospital, Oslo


Cezary Cybulski, Jan Lubinski, Dominika Wokolorczyk—International Hereditary Cancer Centre, Szczecin


Manuel Teixeira, Sofia Maia, Ana Peixoto, Rui Henrique, Jorge Oliveira, Nuno Gonçalves, Luís Araújo, Manuela Seixas, João Paulo Souto, Pedro Nogueira—Portuguese Oncology Institute, Porto


Lucia Copakova—National Cancer Institute, Bratislava


Janez Zgajnar, Mateja Krajc, Alenka Vrecar—Institute of Oncology, Ljubljana


Gabriel Capellá, Ignacio Blanco—Hereditary Cancer Program, Catalonian Institute of Oncology, Barcelona

Teresa Ramón y Cajal, David Fisas, Josefina Mora, Salvador Esquena—Hospital de Sant Pau, Barcelona

Judith Balmaña, Neus Gadea, Juan Morote—Hospital Vall d'Hebron, Barcelona


Annelie Liljegren, Marie Hjälm -Eriksson, Karl-Johan Ekdahl, Stefan Carlsson—Karolinska University Hospital, Karolinska Institutet, Stockholm

United Kingdom

Angela George, Zoe Kemp, Jennifer Wiggins, Cathryn Moss, Vincent Khoo, Nicholas Van As, Alan Thompson, Chris Ogden, Christopher Woodhouse, Pardeep Kumar—Royal Marsden NHS Foundation Trust

D Gareth Evans, Barbara Bulman, Jeanette Rothwell, Karen Tricker—Manchester Regional Genetics Service, Manchester

Diana Eccles, Gillian Wise, Catherine Mercer, Donna McBride, Philandra Costello, Allison Pearce, Audrey Torokwa—Wessex Clinical Genetics Service, Southampton.

Marc Tischkowitz, Joan Paterson, Virginia Clowes, Amy Taylor, Barbara Newcombe—East Anglian Regional Genetics Service, Cambridge

Lisa Walker, Dorothy Halliday, Barbara Stayner, D Fleming-Brown—Oxford Regional Genetics Service, Oxford

Katie Snape, Helen Hanson, Shirley Hodgson, Glen Brice, Tessa Homfray, Carrie Hammond, Kelly Kohut, Uruj Anjum, Audrey Dearing, Mark Mencias—South West Thames Regional Genetics Service, London.

Carole Brewer, Alison Potter, Caroline Renton, Anne Searle, Kathryn Hill, Selina Goodman, Lynda Garcia, Gemma Devlin, Sarah Everest, Maria Nadolski—Peninsula Clinical Genetics Service. Exeter.

Alex Henderson, Fiona Douglas, Irene Jobson, Edgar Paez—Northern Clinical Genetics Service, Newcastle.

Alan Donaldson, Sue Tomkins—South West Regional Genetics Service, Bristol

Caroline Langman, Chris Jacobs, Gabriella Pichert, Adam Shaw, Anju Kulkarni, Vishakha Tripathi, Sarah Rose, Cecilia Compton, Michelle Watson and Cherylin Reinholtz—South East Thames Regional Genetics Service, Guys Hospital London

Angela Brady, Virginia Clowes, Huw Dorkins, Athalie Melville, Monika Kosicka-Slawinska, Carole Cummings, Vicki Kiesel, Marion Bartlett, Kashmir Randhawa, Natalie Ellery—North West Thames Regional Genetics Service, Harrow

Lucy Side, Alison Male, Kate Simon, Katie Rees, Cecilia Compton, Lizzie Tidey, Jana Gurasashvili—North East Thames Regional Genetics Service, NE Thames.

Jackie Cook, Louise Nevitt, Stuart Ingram, Alice Howell—North Trent Clinical Genetics Service, Sheffield

Derek Rosario, James Catto, Joanne Howson—Academic Urology Unit, Sheffield

Rachel Hart, Kai-Ren Ong, Cyril Chapman, Trevor Cole, Tricia Heaton, Jonathan Hoffman, Lucy Burgess, Wayne Glover, Camilla Huber—West Midlands Regional Clinical Genetics Service, Birmingham

Rosemarie Davidson, Mark Longmuir, Cathy Watt, Alexis Duncan—West of Scotland Genetics Service, Glasgow

Julian Barwell, Roger Kockelbergh, Shumikazi Mzazi, Amy Dineen, Ayisha Sattar, Beckie Kaemba, Zahirah Sidat, Nafisa Patel, Kas Siguake—Leicester Royal Infirmary

Alex Henderson, Angela Birt, Una Poultney, Nkem Umez-Eronini, Jaswant Mom—North Cumbria University Hospitals Trust

Lynn Greenhalgh, Vivienne Sutton—Cheshire and Mersey Clinical Genetics Service, Liverpool Women’s Hospital

Philip Cornford, Nicola Bermingham, Pembe Yesildag, Katy Treherne, Julie Griffiths—Royal Liverpool and Broadgreen Hospital NHS Trust, Liverpool

Carole Brewer, Lyn Cogley, Hannah Gott—Derriford Hospital, Plymouth

United States

Dr Wendy S Rubinstein, Dr Peter Hulick, Dr Michael McGuire, Dr Daniel Shevrin, Dr Karen Kaul, Scott Weissman CGC, Anna Newlin, Kristen Vogel, Shelly Weiss, Nicole Hook—NorthShore University HealthSystem, Evanston

Saundra Buys, David Goldgar, Tom Conner, Vickie Venne, Robert Stephenson, Christopher Dechet—Salt Lake City, Utah

Susan Domchek, Jacquelyn Powers, Neil Rustgi—University of Pennsylvania, Philadelphia

Sara Strom, Banu Arun, John W. Davis, Yuko Yamamura—MD Anderson, Texas

Elias Obeid, Veda Giri, Laura Gross, Linda Okoth—Fox Chase Cancer Center

Kathy Cooney, Elena Stoffel, Linda Oko—University of Michigan

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