Men at High Genetic Risk for Prostate Cancer

Background:

Prostate cancer is the most common malignancy and the second leading cause of cancer-related deaths in American men.

Prostate cancer has substantial inherited predisposition and certain genetic variants that are associated with an increased risk of prostate cancer.

An evolving approach to prostate cancer screening is to target populations at risk of developing prostate cancer based on their genetic predisposition.

Objective:

To follow the natural history of men with known germline variants or likely pathogenic variants in genes that put them at risk for developing prostate cancer.

Eligibility:

Males between ages 30-75 years old.

Documented germline pathogenic or likely pathogenic variants in prostate cancer-related risk gene: BRCA 1 and 2, DNA Mismatch Repair (MMR) genes associated with Lynch syndrome (MLH1, MSH2, MSH6, PMS2, and EPCAM), HOXB13, ATM, NBN, TP53, CHEK2, PALB2, RAD51C, RAD51D, BRIP1, or FANC (FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, and FANCM).

Must be able and willing to provide informed consent.

Design:

Up to 500 subjects will be enrolled.

Participants will undergo sampling of blood for prostate-specific antigen. Based on these results and age, participants will be considered for biopsy and/or continued monitoring if feasible upon clinical discretion.

Participants will undergo a baseline MRI evaluation with follow-up scans every 2 years as clinically indicated.

Following initial evaluation, participants will be followed as clinically indicated, usually at 12 month intervals, to determine their PSA level, prostate cancer treatment (if relevant) and/or disease/survival status until death.

• Inclusion Criteria:
• Males between ages 30-75 years old.
• Documented germline variant (i.e. pathogenic/likely pathogenic variant) in prostate cancer risk-related gene from a CLIA certified laboratory: BRCA1 and BRCA2, MMR genes (MLH1, MSH2, MSH6, PMS2, and EPCAM) associated with Lynch syndrome, as well as HOXB13, ATM, NBN, TP53, CHEK2, PALB2, RAD51C, RAD51D, BRIP1, or FANC (FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, and FANCM).
• Prognosis of >5 years survival if affected by another cancer
• Ability of subject to understand and the willingness to sign a written informed consent document

Exclusion criteria

• Prior diagnosis or treatment for prostate cancer
• Known contraindication to MRI:

• Participants unable to fit through MRI scanner (radiologist discretion)
• Allergy to MR contrast agent
• Participants with pacemakers, cerebral aneurysm clips, shrapnel injury, or implantable electronic device
• Active concomitant medical or psychological illnesses that may increase the risk to the subject or inability to obtain informed consent, at the discretion of the principal investigator.