Genes of Relevance to Prostate Cancer
The following genes have varying degree of association to inherited prostate cancer risk. Some of these genes have been associated with aggressive prostate cancer, and are found in higher rates among men with metastatic prostate cancer. Prostate cancer treatment, management, or screening recommendations are available for some of these genes but not all. Additional cancer risks may also be identified based upon the genes tested. Clinical trials may also be available for men with prostate cancer who test positive for genetic mutations in specific genes.
BRCA1-BRCA2
Cancer Risks
For Men: Prostate cancer (aggressive prostate cancer for BRCA2), pancreatic cancer, male breast cancer, and melanoma;
For Women: Hereditary breast and ovarian cancers, pancreatic cancer, peritoneal cancer and melanoma.
Screening and Management
Prostate Cancer: Specific treatment / Clinical Trial options are emerging or exist for men with advanced or metastatic prostate cancer who carry BRCA mutations. BRCA status may also be included in discussions of active surveillance for early-stage prostate cancer. Prostate cancer screening is recommended to begin at age 40.
Men with metastatic, castration-resistant prostate cancer who carry mutations in specific DNA repair genes may be considered for treatment with PARP inhibitors. These genes include: BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PP2R2A, RAD51B/C/D, RAD54L. Men with metastatic, castration-resistant prostate cancer may discuss with their doctor if a PARP inhibitor may be considered for their care.
Pancreatic Cancer: Consultation with a gastroenterologist may be recommended to discuss pancreas imaging, especially if there is a family history of pancreatic cancer.
Melanoma: Consult with a dermatologist for skin exams and wearing sun protection.
Male breast cancer: Clinical breast exams starting at age 35, usually by a breast surgeon.
Breast cancer for women: Several recommendations exist for women with BRCA mutations, including earlier breast cancer screening, addition of MRI to mammogram, chemoprevention, and risk-reducing surgery options.
Ovarian cancer: Options to reduce risk, such as risk-reducing surgery, exist. Women who carry BRCA mutations are encouraged to speak to a gynecologic surgeon about this option.
Reproductive: If two individuals with a BRCA mutation have a child, there is a chance that the child may develop Fanconi anemia. Carriers of a BRCA mutation are encouraged to seek genetic counseling prior to conceiving.
Additional recommendations are based upon a patient’s mutation, personal and family history.
Images reflect cancers relevant to men only
HOXB13
Cancer Risks
Prostate Cancer: Associated with hereditary prostate cancer, increased lifetime risk, and younger onset of prostate cancer.
Screening and Management
Prostate Cancer: No current guidelines exist for prostate cancer screening based on HOXB13 status. Expert opinion supports considering prostate cancer screening at a younger age (such as age 40-45).
Additional recommendations are based upon a patient’s mutation, personal and family history.
Men with metastatic, castration-resistant prostate cancer who carry mutations in specific DNA repair genes may be considered for treatment with PARP inhibitors. These genes include: BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PP2R2A, RAD51B/C/D, RAD54L. Men with metastatic, castration-resistant prostate cancer may discuss with their doctor if a PARP inhibitor may be considered for their care.
Images reflect cancers relevant to men only
MLH1-MSH2-MSH6-PMS2-EPCAM
Cancer Risks
Associated with Lynch Syndrome
Colorectal Cancer, Endometrial Cancer (women only), Ovarian Cancer (women only), Pancreatic Cancer, Gastric Cancer, Upper intestinal cancer, Prostate Cancer (men only), Upper urinary tract (urothelial) cancers, brain tumors
Screening and Management
Prostate Cancer: Screening recommendations for prostate cancer do not currently exist but depending on mutation status and family history, screening may be recommended to start at the age of 40-45. Specific treatment / Clinical Trial options are emerging for men with advanced or metastatic prostate cancer based upon mutations in these genes.
Men with metastatic, castration-resistant prostate cancer who carry mutations in specific DNA repair genes may be considered for treatment with PARP inhibitors. These genes include: BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PP2R2A, RAD51B/C/D, RAD54L. Men with metastatic, castration-resistant prostate cancer may discuss with their doctor if a PARP inhibitor may be considered for their care.
Colon Cancer: Screening is recommended at a young age, starting at 20-25 for mutation carriers with repeat colonoscopy every 1-2 years.
Endometrial and Ovarian Cancer: Risk-reducing medical and surgical options are available. Women are encouraged to talk to their doctor about these options.
Gastric, Upper Intestinal, and Pancreatic Cancers: Options for endoscopy and imaging can be discussed with a gastroenterologist.
Urinary tract cancer: Consider urinalysis starting at age 25-30. Imaging may also be discussed with a urologist.
Brain tumors: Annual neurologic exam starting at 25-30.
Reproductive: If two individuals with a mutation in one of these genes have a child, there is a chance that the child may develop a condition called constitutive mismatch repair deficiency. Carriers of mutations in these genes are encouraged to seek genetic counseling prior to conceiving.
Additional recommendations are based upon a patient’s mutation, personal and family history.
Images reflect cancers relevant to men only
ATM
Screening and Management
Prostate Cancer: There are no screening guidelines for men with ATM mutation and screening recommendations are based upon family history at this time. Mutations may inform options for treatment or clinical trials.
Men with metastatic, castration-resistant prostate cancer who carry mutations in specific DNA repair genes may be considered for treatment with PARP inhibitors. These genes include: BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PP2R2A, RAD51B/C/D, RAD54L. Men with metastatic, castration-resistant prostate cancer may discuss with their doctor if a PARP inhibitor may be considered for their care.
Breast Cancer: For men, currently guidelines do not exist but self-breast exams may be considered. Men may also consider clinical breast exams starting in their mid-to-late thirties with their doctor. Women are recommended to have a mammogram and breast MRI based on mutation status and family history.
Pancreatic Cancer: Men and women with ATM mutations have an increased risk for pancreatic cancer. The exact risk is not known but it is probably higher in families where there is a past history of one or more people who have had pancreatic cancer. Individuals with ATM mutations may consider consultation with a gastroenterologist to discuss imaging options, especially if there is a family history of pancreatic cancer.
Reproductive: If two individuals with an ATM mutation have a child, there is chance that the child may develop ataxia-telangiectasia. Carriers of an ATM mutation are encouraged to seek genetic counseling prior to conceiving.
Additional recommendations are based upon a patient’s mutation, personal and family history.
Images reflect cancers relevant to men only
PALB2
Cancer Risks
For Men and Women: Pancreatic Cancer
For Women: Breast cancer
For Men: Limited data regarding association to prostate cancer risk at this time. However, mutations may be found in men with metastatic prostate cancer and may help inform treatment options.
Screening and Management
Prostate Cancer: Specific treatment / Clinical Trial options are emerging or exist for men with advanced or metastatic prostate cancer who carry PALB2 mutations.
Men with metastatic, castration-resistant prostate cancer who carry mutations in specific DNA repair genes may be considered for treatment with PARP inhibitors. These genes include: BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PP2R2A, RAD51B/C/D, RAD54L. Men with metastatic, castration-resistant prostate cancer may discuss with their doctor if a PARP inhibitor may be considered for their care.
Female Breast Cancer: Mammograms and annual breast MRI are recommended starting at age 30.
Pancreatic Cancer: There are currently no guidelines for screening for pancreatic cancer, though imaging of the pancreas is available. Discussion with a high-risk gastroenterologist may be considered.
Reproductive: If two individuals with a PALB2 mutation have a child, there is chance that the child may develop Fanconi anemia. Carriers of a PALB2 mutation are encouraged to seek genetic counseling prior to conceiving.
Additional recommendations are based upon a patient’s mutation, personal and family history.
Images reflect cancers relevant to men only
CHEK2
Cancer Risks
Men and Women: Thyroid Cancer, Colon Cancer
For Women: Breast Cancer
For Men: Prostate Cancer (emerging data)
Screening and Management
Prostate Cancer: No guidelines for screening based on CHEK2 mutations are available at this time. Screening recommendations are typically based on personal and family history. Mutations may be found in men with metastatic prostate cancer and may help inform treatment options.
Men with metastatic, castration-resistant prostate cancer who carry mutations in specific DNA repair genes may be considered for treatment with PARP inhibitors. These genes include: BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PP2R2A, RAD51B/C/D, RAD54L. Men with metastatic, castration-resistant prostate cancer may discuss with their doctor if a PARP inhibitor may be considered for their care.
Colon Cancer: Colonoscopies are recommended based on mutation status and family history.
Thyroid Cancer: Physical exam and thyroid ultrasound may be considered for patients with CHEK2 mutations.
Additional recommendations are based upon a patient’s mutation, personal and family history.
Images reflect cancers relevant to men only
NBN
Cancer Risks
For Men: Prostate Cancer (emerging data)
For Women: Female Breast Cancer
Screening and Management
Prostate Cancer: Currently not a part of prostate cancer screening guidelines. Base screening on family history.
Female Breast Cancer: Women are recommended to have mammograms and breast MRI based on mutation status and family history.
Men with metastatic, castration-resistant prostate cancer who carry mutations in specific DNA repair genes may be considered for treatment with PARP inhibitors. These genes include: BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PP2R2A, RAD51B/C/D, RAD54L. Men with metastatic, castration-resistant prostate cancer may discuss with their doctor if a PARP inhibitor may be considered for their care.
Reproductive: If two individuals with an NBN mutation have a child, there is a chance that the child may develop a condition called Nijmegen breakage syndrome. Carriers of an NBN mutation are encouraged to seek genetic counseling prior to conceiving.
Additional recommendations are based upon a patient’s mutation, personal and family history.
Images reflect cancers relevant to men only
Treatment with PARP inhibitors
Men with metastatic, castration-resistant prostate cancer who carry mutations in specific DNA repair genes may be considered for treatment with PARP inhibitors. These genes include: BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PP2R2A, RAD51B/C/D, RAD54L. Men with metastatic, castration-resistant prostate cancer may discuss with their doctor if a PARP inhibitor may be considered for their care.