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Prostate Cancer and Genetic Testing

Genetics has for some time been known to play a key role in inheritance of prostate and breast cancer.  However, after sequencing of the human genome, it has become more evident that genetics also play a role in the risk of developing prostate cancer, cancer agressiveness, and the treatment responsiveness. 


This year nearly 248,530 men in the United States will be diagnosed with prostate cancer. More than 34,130 will die from the disease. The risk of prostate cancer is 76 percent higher in Blacks than in Caucasian and the death rate even 114 percent higher. This disparity is even further demonstrated advanced forms of prostate cancer.


Men in general have a 1 in 9 chance of being diagnostic with prostate cancer. In contrast, the incidence increases to a 1 in 6 chance for Black men. About 5 to 10 percent of all prostate cancers found are hereditary, which suggests that there is a greater chance of the prostate cancer occurring in the family. This is supported by the fact that men with a family history (e.g. father, brother, uncle) of the disease have a 1 in 5 chance of getting prostate cancer. Furthermore, if family members have breast cancer or ovarian cancer, a man’s risk may increase also.


In addition to an increase in incidence, prostate cancers with inherited genetic mutations are found more aggressive than those cancers found in men without inherited mutations. It is now known that genetic mutations can influence prostate cancer in the following ways:



•     Increase risk of developing cancer


•     Can cause cancer to behave more aggressively


•     Can affect how patients respond to specific treatments


On occasion, the genetic mutations are not passed on from a relative, but rather arises in the prostate cancer and stays within the tissue. These types of mutations are called somatic mutations, which can hel)p guide treatment options. Doctors may decide whether to suggest genetic testing based on the aggressiveness on the individual’s cancer.


The National Comprehensive Cancer Network (NCCN), a not-for-profit group representing many leading cancer centers, suggests an individual should undergo a germline (familial) test if he has a Gleason score of seven or higher and at least one of the following: 


•     African American


•     High-risk, very-high-risk, regional, or metastatic prostate cancer 


•     Ashkenazi Jewish ancestry

•     Family history of high-risk germline mutations (e.g. BRCA1/2, Lynch mutation)


•     A positive family history of cancer:


•     A strong family history of prostate cancer consists of brother or father or multiple family members who were diagnosed with prostate cancer at less than 60 years of age or who died from prostate cancer


•     Or three or more cancers on same side of family, especially diagnoses less than 50 years of age: bile duct, breast, colorectal, endometrial, gastric, kidney, melanoma, ovarian, pancreatic, prostate, small bowel, or urothelial cancer. 
 


Somatic Tumor Testing is recommended when there is a need to look for tumor genetic changes in genes such as BRCA1, BRCA2, or ATM, PALB2, FANCA, RAD51D, CHEK2, and CDK12, in patients with metastatic prostate cancer. This testing can be considered in men with regional prostate cancer.


The information collected from genetic testing allows doctors to better design an individual’s therapeutic plan, which may involve a new class of drug called PARP inhibitors. Clinical trials have shown that PARP inhibitors may be useful in treating inherited prostate cancer. In addition to this new class of drugs, certain chemotherapeutic and immunotherapeutic treatments are found more effective in individuals with genetic mutations.

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