RecruitingNCT02543905

The PROFILE Study: Germline Genetic Profiling: Correlation With Targeted Prostate Cancer Screening and Treatment

Sponsor

Institute of Cancer Research, United Kingdom

Enrollment

1,600 participants

Start Date

Mar 9, 2015

Study Type

OBSERVATIONAL

Conditions

Prostate Cancer Prostate Biopsy Genetic Counselling Genetic Markers

Summary

Prostate cancer is now the most common cancer in men in the Western world. In the United Kingdom (UK), there were over 52,000 new cases diagnosed in 2016-2018 and a lifetime risk of 1 in 8. Prostate cancer (PrCa) can run in some families and research studies have identified several genetic changes in Caucasian populations that are thought to increase the risk of developing prostate cancer. Other studies have shown that men from certain ethnic groups also have a higher risk of prostate cancer, and this includes men of black African or black African-Caribbean ancestry. This study aims to look at men with a higher risk of prostate cancer based on their ethnicity, family history and/or genetic predisposition to see whether any of these genetic changes are present in their DNA (genetic material) and whether this could be a helpful screening tool in prostate cancer screening programmes. It is thought that many genetic changes are involved in the development of prostate cancer and research is being carried out worldwide to identify these genetic changes. Some of these changes may cause a very slight increase in prostate cancer risk while others may cause a much larger increase in risk of developing prostate cancer. The investigators will invite (i) men of any ethnicity with a family history of prostate cancer; (ii) men of black African or black African-Caribbean ancestry; and (iii) men of any ethnicity with a known genetic predisposition to having prostate cancer (e.g., being known to have inherited a gene mutation that increases risk of prostate and/or being known to be in the top tenth percentile of the polygenic risk score (high PRS score prior to enrolment) for targeted prostate screening (Prostate Specific Antigen (PSA) testing, MRI and a biopsy of the prostate gland) and genetic profiling. The outcome of these prostate cancer screening investigations will be compared with the genetic profiles of those taking part in the study in order to look for certain genetic changes in the gene code that are thought to increase prostate cancer risk. This research will help us to determine what the role of such genetic profiling is in a prostate cancer screening programme and if it helps identify men at high prostate cancer risk.

Eligibility

Sex: MALEMin Age: 40 YearsMax Age: 69 Years

Inclusion Criteria13

Either:
Men of any ethnicity with a positive family history of PrCa defined as:
Men with a first degree relative (or second degree if through female line) with histologically or death certificate proven PrCa diagnosed at \<70 years
Men with two relatives on the same side of the family with histologically or death certificate proven PrCa where at least one is diagnosed at \<70 years
Men with three relatives on the same side of the family with histologically or death certificate proven PrCa diagnosed at any age
Or
Men of black African or black African-Caribbean ancestry defined as:
Both parents and all 4 grandparents being of either black African or black African-Caribbean ancestry.
Or
Men of any ethnicity with a genetic predisposition to having prostate cancer e.g., being known to have inherited a gene mutation that increases risk of prostate cancer (e.g. BRCA1, BRCA2, ATM, PALB2, MLH1, MSH2, MSH6, CHEK2 and other DNA repair gene mutations as listed in the study protocol); and/or being known to have a high polygenic risk score (PRS) (defined as being in the top tenth percentile prior to enrolment).
Age 40- 69 years
WHO performance status 0-2
Absence of any psychological, familial, sociological or geographical situation potentially hampering compliance with the study protocol and follow up schedule.

Exclusion Criteria8

Previous cancer with a life expectancy of less than five years.
Previous PrCa
Negative biopsy within one year before recruitment
Co-morbidities making prostate biopsy risk unacceptable (anticoagulants or antiplatelet medication including Warfarin, Clopidogrel, Apixaban, Dabigatran or other NOAC (Novel Oral Anti-Coagulant); poorly controlled diabetes, cardiovascular/respiratory disease, immunosuppressive medication or splenectomy)
Men with body mass index (BMI) 40 and above.
Men with BMI 35 and above plus other co-morbidities.
Contraindications to having an MRI (non-MRI compliant pacemakers, aneurysm clips, metallic cardiac valve/stent, Ventriculo-Peritoneal (VP) shunt, cochlear implant, neurotransmitter, metallic foreign bodies in eye(s), other metalwork, claustrophobia)
Any significant psychological conditions that may be worsened or exacerbated by participation in the study

Interventions

PROCEDUREProstate MRI and Biopsy

All men will be offered a MRI and prostate biopsy and they can either opt to undergo these procedures at baseline irrespective of PSA level at baseline or they can undergo PSA-only screening until clinically indicated based on an age-defined PSA threshold, at which point, they will undergo prostate MRI and biopsy once their PSA reaches the threshold.