Prostate cancer genetic testing: the inherited genes, who should test, and what it can’t find

It reads the DNA a man was born with for variants that raise the chance of prostate cancer. It looks for inherited risk, not for cancer, and the same variants often matter for his relatives too.

Inherited risk comes in two kinds. For most men it is spread across hundreds of common variants, each raising risk only slightly. For a smaller number it comes from one rare, harmful variant in a particular gene, and that second kind is what genetic testing looks for.^[1]

This is general science about genes and prostate cancer, not a list of what any one test checks.

• BRCA2, and BRCA1. Prostate cancer is seen more often in men who carry a harmful BRCA2 variant than in men overall.^[1] NCI puts numbers on it: about 19% to 61% of men with a harmful BRCA2 variant, and 7% to 26% with a harmful BRCA1 variant, get prostate cancer by age 80, against about 10.6% of all men.^[2]
• The mismatch repair genes. Men with an inherited variant in MLH1, MSH2, MSH6 or PMS2, the genes behind Lynch syndrome, have a higher risk of prostate cancer.^[1]
• ATM, CHEK2 and PALB2. With BRCA1, BRCA2 and the mismatch repair genes, these are among the genes that, as NCI reports, the NCCN prostate cancer guideline says a germline test should include.^[1]
• HOXB13, the first gene found to be linked with hereditary prostate cancer, and one NCI reports on NCCN’s list,^[1] is not one that GeneCancer, our at-home genotyping of selected variants, looks at.

A result with no variant found can’t rule out inherited cancer risk.

• Men with prostate cancer that has spread. Guidelines recommend testing every man diagnosed with metastatic prostate cancer, NCI notes, and the result can guide treatment choices.^[3]
• Men with prostate cancer and related cancers in the family. The guidelines NCI summarises look at relatives on the same side of the family with breast cancer at 50 or younger, ovarian or pancreatic cancer, breast cancer in a man, or prostate cancer that was high-risk or had spread.^[1]
• Families that already meet the criteria for hereditary breast and ovarian cancer or Lynch syndrome, or have a known variant.^[1]
• Men without prostate cancer who have a family history. A father or brother with prostate cancer means about two to three times the risk, and a family with both prostate and breast or ovarian cancer raises it further.^[1] A clinician or genetic counselor can say whether testing fits.

NCI’s summary also recommends genetic counseling before a germline test.^[1] The family patterns behind other inherited cancers are on our hub page.

Checks selected variants across 108 genes, including BRCA1 and BRCA2, by genotyping. The genes linked with prostate cancer are the general science above; which variants it checks in each of the other genes on its list isn’t published yet. It reads chosen positions rather than whole genes, so a harmful variant elsewhere would go unseen, and finding none can’t rule out inherited risk.

Selected variants only, by genotyping. Not a full-gene test.

It doesn’t check HOXB13.

If you or a close relative has had cancer, ask your doctor about full-gene clinical testing.

• A harmful variant found. It raises your chance of prostate cancer, and depending on the gene, of other cancers too. Before acting on a finding from a test of selected variants, have a clinical test confirm it.^[5]
• Your daughters as well as your sons. A BRCA variant passes to each child with a 1 in 2 chance,^[4] so a man’s result can matter for his daughters’ breast and ovarian cancer risk as much as for his sons’.
• Why a family’s cancers cluster. A family history of breast cancer is linked with higher prostate cancer risk, and a family history of prostate cancer with higher breast cancer risk in women.^[1]
• Nothing found, or an uncertain result. A negative covers only what was read. A variant of uncertain significance is one nobody can yet call harmful or harmless, so your clinician weighs it, like a negative, against your family history.^[3]

• Whether you have prostate cancer. A gene result reads inherited risk. Symptoms, or questions about checking for prostate cancer, are for your doctor.
• Most of your inherited risk. For most men that is spread across many common variants, which a result for single genes doesn’t capture.^[1]
• Whether you will get cancer. Even with a harmful BRCA2 variant, many men never develop prostate cancer.^[2]
• What to do about it. Checks, treatment and any other choices belong with your clinician, after confirmation.

If you have prostate cancer, or related cancers run in your family, start with your clinician or cancer care team and a test that reads each gene end to end.

With no personal or family history of cancer, GeneCancer can show which, if any, of its selected variants you carry, by genotyping. Because it reads chosen positions, finding none doesn’t rule out inherited risk, and a variant it finds is one to confirm with your clinician through a clinical test.

Selected variants only, by genotyping. Not a full-gene test.