Is I am at risk of getting Prostate cancer or other cancer if my parent have cancer? Who can be screened for possibility or presence of Hereditary Prostate Cancer?

 Is I am at risk of getting cancer if....................? Mostly children (sometime parents) ask this question. Today again. So, i tried to explain them that Usually NOT.  About 10% of cases can be hereditary. Generally, if a person having some special pathology and risk factors then he is suspected for familial cancer. 

Risk factors for possibility of presence of genetic mutation are-

A. If your brother or father has been detected for high risk, advanced or metastatic prostate cancer at age below 60 year, 

B. Biopsy is having intraductal or cribriform pattern, 

C. If first degree relative died of Prostate Cancer. 

Investigation for testing of presence of Genetic mutation-

If above, then send family member for counseling with "Genetic counselor". Based on case history and available facts, he may decide need of "Germline" or "Somatic" testing for presence of pathogenic mutation that are responsible for developing cancer. These genetic mutations are Lynch syndrome causing mutations or HRRm (Homologous Recombination Repair Gene Mutation). HRRm are BRCA1, BRCA2, ATM, BARD, BRIP, CPK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, RAD54C.  Presence of MLH1, MSH2, MSH6, PMS2 confirms Lynch syndrome. 

Mostly, these are associated with various cancers (e.g. Breast cancer, Bile duct cancer, Endometrial carcinoma, Ovarian cancer, Colon, Urothelial, Kidney, Melanoma,, Pancreatic cancer, Prostate cancer) having Ductal, intraductal or cribriform histopathology.  They are helpful in planning of treatment if recommended routine treatment options failed. For example, Olaparib- in presence of HRRm, Rucaparib- in BRCAm and pembrolizumab- in MSI-H, dMMR. 

Sometime, rare genes are also tested like HOXB13, PPP2P2A. It may helpful in treatment planning. Olaparib is not recommended in presence of PPP2R2A mutation. However, HOXB13 is associated with early age prostate cancer.   

Testing of Germline mutation is done in blood or saliva. Test is called NGS (Next Generation Sequencing).  Hundreds of pathogenic mutation are explored till today. They are either associated with development of different type of cancer or resistant to medicine or may cause progression. Thousands of mutation are detected but their role is unknown. Some of mutations are Drugable that means treatable. If these mutation happened in DNA then they may be carried by children. When these mutation get triggered by unknown factors they may produce cancer. 

Genetic testing is recommended for patients with prostate cancer if they have-

1. Ashkenazi Jewish

2. Positive family history (means if father or brother or many family members are diagnosed to have high risk prostate cancer at young age (below 60 year of age) or diet of prostate cancer. Or, more than 3 types of cancers (Breast, Bile duct, Pancreatic, Gastric, Small intestine, Colon, Rectal, Kidney, Urothelial, Advanced Prostate, Endometrial, Ovarian, Melanoma) present in same side of family members (blood relation) who suffered before age of 50 years.   

3. High risk or above (regional or metastatic) prostate cancer

4. Cribriform or Ductal / intraductal histology

Somatic testing-

In absence of valid recommendation for genetic testing, testing for "Somatic mutation" is done. These mutations are tested in tumour tissue and can be done by Immunohistochemistry (IHC) or NGS. It have potential to uncover genetic mutations but over-interpretation of possibility of genetic mutation should not be done. If anyone suspecting genetic mutation then it is better to do genetic mutation testing as no test is designed to do over-interpretation. Somatic testing may need to be repeated if cancer progress.  

Somatic testing for HRRm can be considered if prostate cancer spread to regional node or metastatic; however MSI-H (Microsatellite instability - high) or dMMR (absence of Mismatch repair gene) are tested in metastatic CRPC (Castration resistant - Prostate cancer). 

You can't prevent possibility of developing hereditary cancer but 

You can enroll yourself for screening of prostate cancer or other cancer. Screening helps in early detection. 10 points to know about screening of prostate cancer and its treatment. 

1. First step for screening is DRE (digital rectal examination)- in this doctor will insert finger inside rectum and try to feel prostate for it size, presence of firm swelling inside prostate. 
2. Second step for screening of prostate cancer is doing Blood test to know level of Serum PSA (both free and total)- it is started at age 45 year (at age 40 year if suspecting familial cancer).
3. If DRE is abnormal and PSA level is above the normal value for particular age (cut off value vary in different countries and different age) then mpMRI (Multiparametric MRI) and biopsy is recommended.
4. Biopsy is procedure where interventional radiologist insert a niddle of biopsy Gun into prostate through rectum (trasrectal) or region between scrotum - anal opening (transperineal) route under guidance of transrectal Ultrasound or MRI. He require to take multiple tissue from different quadrants of prostate (minimum 12 quadrant) .
5. If DRE is normal and PSA value is below 1 ng/ml then once may continue screening every 2-4 yearly, if PSA value is <3 ng/ml then 1-2 yearly. 
6. There are some data suggesting "a cut off value of 6 ng/ml" in Indian people. 
7. Biopsy showing presence of Intraductal carcinoma, Atypical intraductal proliferation (AIP), Atypia, High grade- Prostatic Intraepithelial Neoplasia (PIN) warrants repeat biopsy at 6 months. 
8. In case of negative biopsy or inconclusive biopsy report, there are some test available that detect presence of biomarker. They predict higher possibility of cancer. Thus warrants repeat biopsy. These are PCA3 in urine, Prostate health index (PHI), 4Kscore, ConfirmMDx, ExoDx Prostate (intelliscore), SelectMDx, MiPs (Mi prostate Score).
9. All detected prostate cancer NOT require treatment. Some of early stage prostate cancer (Very low risk, low risk or favorable risk prostate cancer can be kept under active surveillance or definitive treatment (discuss with your oncologist or urologist). 
10. There are some commercial genetic test (Prolaris, Oncotype DX prostate, Decipher, Promark) are also available that may help in prognostication and decision of observation vs treatment in case of post biopsy very low risk and low risk prostate cancer. Prolaris (Quantitative RT PCR for 31 prostate cancer specific genes) and Oncotype DX prostate (12 prostate cancer specific genes) can be used in "post biopsy- favorable risk prostate cancer (PCa-FR)". However, Decipher test (whole trascriptome 1.4M RNA expression) can be used in Post radical prostatectomy (RP) case with pT2 margin positive, any pT3 and rising PSA (above nadir)