Trial Information

UK Genetic Prostate Cancer Study: Epidemiology and Molecular Genetics Studies

The study is divided into two parts:

1. The Study at The Royal Marsden NHS Foundation Trust, London and Sutton:

The study will be offered to every patient attending the prostate clinics at The Royal
Marsden NHS Foundation Trust, London and Sutton. This is called 'The Systematic Study'.

Patients are approached in the clinic and are given an information sheet and the study
is also explained verbally. They are asked for 18ml of blood and asked to fill out a
family history and epidemiological questionnaire. Those who have not had any treatment
will also be asked for 18ml blood for serum and plasma marker studies.

Those patients with one relative affected with PrCa where one is ≤ 65 years at
diagnosis or a total of 3 or more relatives with PrCa at any age, will be asked if
their relatives can be approached to be asked to give a blood sample for DNA analysis
for PrCa predisposition genes and tumour samples for molecular analyses for PrCa
predisposition and behaviour as outlined above. Where relatives with PrCa are deceased,
pathology records and tumour blocks will be requested after obtaining details of where
they were treated via the index case.

Consent Consent will be sought prospectively from living individuals accrued into the
study from January 2006 to access medical records and tumour blocks.

This study has been active since 1992 and all blood samples have informed consent for
PrCa predisposition gene studies. Outside tumour blocks and pathological samples have
informed consent for molecular studies. Many of The Royal Marsden NHS Foundation Trust
PrCa tumour samples also have consent under a clause in the operation consent form in
use at that time that 'material removed may be used for research purposes'. Some tissue
was collected from local hospitals under the auspices of the previous protocol and the
consent form did not explicitly state separate consent for the use of tissue at that
time, although it was part of the approved protocol. Many patients are now deceased. It
is therefore proposed that tissue and medical record data collected retrospectively
will be analysed anonymously with no results fed back to patients as this would not
impact upon their care. An exception is results from the studies on blood where
findings in PrCa predisposition genes could have implications for relatives.

Those patients who are still living who have previously taken part in the study from
1992 until the present and who have not taken part in the environmental questionnaire
part of the study will be invited to take part in this part of the study. New consent
will be obtained for this.

2. The Study at Collaborative Centres throughout the UK. Many of these are via the NCRN
network.

This is conducted as for the Study at The Royal Marsden except the study is explained
verbally and then if the patient is interested, their details are given to the study office
by confidential fax and the study office sends the patient an information sheet and consent
form.

Furthermore, the only groups of patients eligible for this part of the study are (a) men
with PrCa presenting at a young age (≤ 60 years) or (b) PrCa in first-degree related pairs
where one is ≤ 65 years at diagnosis or (c) a total of 3 or more relatives with PrCa at any
age

The two parts (1) and (2) are now called the UKGPCS (UK Genetic Prostate Cancer Study).

There are currently over 300 collaborators UK-wide participating under the auspices of the
previous protocol (previously, The Cancer Research UK/British Prostate Group//British
Association of Urological Surgeons Section of Oncology and NCRN Familial Prostate Cancer
Study).

Proposed analyses on the samples The samples will be used to find PrCa predisposition genes
using linkage and other analyses. These investigations are solely for research to find a
prostate cancer-predisposing gene and no results would be conveyed to the patients until
such a gene(s) had been found. If such a gene(s) is found, then no patient will have
genetic testing for abnormalities in such a gene without prior genetic counselling and this
would be on a newly taken blood sample. Only those patients who wish (as stated on their
consent form) to be informed of research findings will be contacted. If this occurs more
than 6 months after the last contact with the patient, this would be via the GP.

Data will be correlated with medical records and treatment outcome to find genetic
alterations that are associated with prostate cancer development and/or prognosis.

Tumour material will be collected and stored at -70oC in freezer space currently available
at The Institute of Cancer Research. Tumour will also be stored in RNA later and paraffin
embedded tumour will be made into tissue microarrays and sections cut. This will be used for
molecular biology analysis.

Cases and their relatives may be flagged by the cancer registry to confirm a diagnosis of
prostate cancer, a date of death and cause of death. This will be done via the Medical
Research Information Service (MRIS), using records maintained by The NHS Information Centre
and the NHS Central Register.

Clinical details are collected routinely as part of the medical care and clinical follow up
record on patients with prostate cancer and these include disease parameters (e.g. stage,
grade) and treatment outcome (e.g. survival data, side effects of treatment). We will also
request follow-up data, approximately 2 years after the patient has consented, to record any
relapse, treatment and survival data that has occurred since diagnosis. We will link the
genetic findings with these clinical data to try to identify genetic markers of disease
parameters (e.g. those which predict for poorer prognosis or worse late toxicity from
treatments such as radiotherapy). These data would be analysed anonymously after linking the
clinical and genetic datasets. No results would be feedback to participants. We will supply
anonymised data from this to an EU dataset (Genepi study). This would only be to a central
database managed under the auspices of GCP and would only be anonymised data. No individual
would be identifiable to the holders of the Genepi database.