Genes linked to aggressive prostate cancer

RELEVANCE

Most relevant for: People diagnosed with advanced prostate cancer.

It may also be relevant for:

people with a genetic mutation linked to cancer risk
people with a family history of cancer
people with prostate cancer

Relevance: Medium-High

Strength of Science: Medium-High

Research Timeline: Post Approval

Relevance rating details

What is this study about?

Experts have found that inherited mutations in several different genes can increase the risk of cancer. This study looked beyond the currently known prostate cancer genes to see whether additional genes are linked to prostate cancer. The study also looked at which genes were most closely linked to aggressive prostate cancer that is more likely to spread.

Why is this study important?

Guidelines recommend genetic testing for anyone diagnosed with prostate cancer or prostate cancer that has a grade of high-risk or very high risk. Results of genetic testing are used to guide screening and treatment and can also be used to help family members understand their cancer risk.

Currently, a few genes are known to increase the risk of prostate cancer. These genes (, , , and ) are included on prostate cancer gene panels. This study found other genes that increase the risk of prostate cancer. The researchers suggest that these genes should be added to current prostate cancer gene panels.

Prostate cancer tumors can be different from one another. In some cases the tumors are slow growing and in other cases they can be more aggressive requiring more intense treatment. Mutations in BRCA2 and possibly other genes have been linked to more aggressive cancers that are more likely to spread beyond the prostate. Prostate cancers that spread can be life-threatening and require more aggressive treatment. Researchers wanted to learn if other gene mutations are likely to cause more aggressive prostate cancer. This information can be used to help guide treatment decisions.

Study findings

Study Population

The study included over 17,000 men of European ancestry with prostate cancer. Just over half had aggressive prostate cancer, and a little less than half had nonaggressive prostate cancer. About a quarter of individuals with aggressive prostate cancer had metastatic prostate cancer (prostate cancer that spreads beyond the prostate into nearby tissues).

Results by gene mutation and prostate cancer type

Gene	People with mutation	People with a mutation who had non-aggressive prostate cancer	People with a mutation who had aggressive prostate cancer	People with a mutation who had metastatic prostate cancer
BRCA2	277 (1.3%)	55 (0.7%)	222 (2.4%)	72 (3.0%)
ATM	202 (1%)	60 (0.7%)	142 (1.6%)	45 (1.9%)
	42 (0.2%)	13 (0.2%)	29 (0.3%)	13 (0.5%)
	27 (0.1%)	7 (0.1%)	20 (0.2%)	4 (0.2%)
XRCC2	10 (0.1%)	2 (0.0%)	8 (0.1%)	2 (0.1%)
MRE11A	23 (0.1%)	11 (0.1%)	12 (0.1%)	6 (0.3%)

BRCA2

277 (1.3%) had a BRCA2 mutation. Of these, 222 (2.4%) had aggressive prostate cancer; 72 people in this group (3.0%) had metastatic prostate cancer. Overall, 55 (less than 1%) had nonaggressive prostate cancer.

ATM

202 (1%) had an ATM mutation. Of these, 142 (1.5%) had aggressive prostate cancer; 45 people in this group (2.0%) had metastatic prostate cancer. Overall, 60 (less than 1%) had nonaggressive prostate cancer.

NBN

42 (0.2%) had an NBN mutation. Of these, 29 (0.3%) had aggressive prostate cancer; 13 people in this group (0.5%) had metastatic prostate cancer. Overall, 13 (0.1%) had non-aggressive prostate cancer. While a link between NBN and aggressive prostate cancer was not statistically significant in this study, the link between NBN and metastatic prostate cancer was significant.

MSH2 and XRCC2

This study found some evidence that inherited mutations in MSH2 and XRCC2 were linked to aggressive prostate cancer, although this link was not as strong as the links with BRCA2, ATM and NBN.

MRE11

This study also found that inherited mutations in MRE11A were linked to metastatic prostate cancer, although this link was not as strong as the links with BRCA2, ATM and NBN.

, , , GEN1 and SLX4

This study found that inherited mutations in TP53, RAD51D, BARD1, GEN1 and SLX4 may also be linked to aggressive prostate cancer, although more research is needed to confirm this.

Other genes: POLK, POLH and MSH5

Inherited mutations in POLK, POLH and MSH5 are very rare. However, this study found that POLK and POLH were linked to aggressive prostate cancer, while inherited mutations in MSH5 were linked to metastatic prostate cancer. More research is needed to verify that these links exist.

Genes not linked to aggressive prostate cancer

HOXB13, CHEK2, and BRCA1 have been linked to increased risk of prostate cancer. However, in this study, these genes were not linked to aggressive prostate cancer. For example, 318 participants (1.8%) had a HOXB13 mutation. Of these, 173 (1.0%) had nonaggressive prostate cancer, compared to 145 (0.8%) who had aggressive prostate cancer.

What does this mean for me?

If you have been diagnosed with prostate cancer, genetic testing for an can help you make treatment decisions. Knowing if you have an inherited mutation can help you and your healthcare team make treatment decisions. It can also help your relatives understand about their risks for cancer.

Current prostate cancer gene panels include BRCA2, BRCA1, ATM, CHEK2 and HOXB13. This study suggests that additional genes should also be included. Adding these genes can benefit those diagnosed with aggressive disease. It may also benefit those diagnosed with prostate cancer at any , as people with an inherited mutation are at risk of developing advanced disease.

Reference

Darst B, Saunders, E, Dadaev, T, et al., sequencing analysis to inform clinical gene panel testing for aggressive prostate cancer. JAMA Oncology; 2023; Published online September 21, 2023.

Wyatt, A. Rare genetic drivers of lethal prostate cancer. JAMA Oncology; 2023; Published online September 21, 2023.

Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.

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posted 2/1/24

Questions To Ask Your Doctor

Should I have genetic testing with a prostate cancer gene panel?
If testing is recommended, what genes are included with the test?
Should I be tested for any other prostate cancer genes that are not included on the recommended prostate cancer gene panel?
How will genetic test results impact my care and treatment?

Guidelines

The National Comprehensive Cancer Network guidelines recommend genetic counseling and testing for the following people with prostate cancer who have:

a tumor test result that suggests an inherited mutation
- for example, a tumor with a BRCA1, BRCA2 or ATM mutation may indicate an inherited mutation in one of those genes
a blood relative who tested positive for an inherited mutation in a gene linked to prostate cancer
metastatic prostate cancer diagnosed at any age
prostate cancer that has spread to the
localized prostate cancer (hasn’t spread beyond the prostate) that is considered very high-risk or high-risk
intermediate-risk prostate cancer with intraductal or cribriform features listed on the
a diagnosis of male breast cancer
Eastern European (Ashkenazi) Jewish ancestry
one or more relatives with:
- breast, colorectal or endometrial cancer diagnosed at age 50 or younger
- male breast cancer, triple negative breast cancer, ovarian cancer or pancreatic cancer at any age
- metastatic, regional, very-high-risk, or high-risk prostate cancer at any age
one or more close relatives with prostate cancer diagnosed at age 60 or younger
three or more relatives on the same side of the family with biliary tract, breast, colorectal, endometrial, glioblastoma, prostate or other cancers

Speak with a genetic counselor if you have questions about whether you meet guidelines for genetic testing.

Updated: 02/01/2024

Peer Support

The following organizations offer peer support services for people with or at high risk for prostate cancer:

FORCE peer support
- Visit our message boards.
  - Once you register, you can post on the Diagnosed With Cancer board to connect with other people who have been diagnosed.
- Sign up for our Peer Navigation Program.
  - Users are matched with a volunteer who shares their mutation and situation.
- Join our private Facebook group.
- Find a virtual or in-person support meeting.
- Join a Zoom community group meeting.

ZERO-The End of Prostate Cancer is a nonprofit organization that provides information and support resources for men with prostate cancer.

Updated: 03/08/2023

Study: Genes linked to aggressive prostate cancer

RELEVANCE

Relevance: Medium-High

Strength of Science: Medium-High

Research Timeline: Post Approval

What is this study about?

Why is this study important?

Study findings

What does this mean for me?

Reference

Questions To Ask Your Doctor

Guidelines

Peer Support

Knowledge Can Save Lives

Study: Genes linked to aggressive prostate cancer

RELEVANCE

Relevance: Medium-High

Strength of Science: Medium-High

Research Timeline: Post Approval

What is this study about?

Why is this study important?

Study findings

What does this mean for me?

Reference

Questions To Ask Your Doctor

Guidelines

Related Resources

Peer Support

Knowledge Can Save Lives