Novel Epigenetic Biomarkers that indicate more severe kinds of Prostate Cancer

About the Research:

Researchers at the Garvan Institute of Medical Research have uncovered new epigenetic biomarkers that predict more severe types of prostate cancer. The use of the biomarkers in conjunction with standard clinical techniques may help physicians develop a more efficient treatment plan and predict if a patient will later develop a more serious and metastatic form of the illness. Men with prostate cancer require more individualized treatments that are based on the characteristics of their tumors, and they cannot get these treatments without new biomarkers that can more accurately predict the likelihood of developing the fatal form of the disease, according to Professor Susan Clark, Head of the Epigenetic Research lab at Garvan and study’s principal investigator.

Risk factors for Prostate Cancer:

Anything that increases the chance of contracting an illness like cancer is considered a risk factor. Risk factors for various malignancies vary. Smoking is one risk factor that may be altered. Others, such as an individual’s age or family history, cannot be changed. However, even if a person has one or more risk factors, it does not mean they will develop the disorder. Others who develop cancer may have had few or no known risk factors, while many people with one or more risk factors never develop the disease. Numerous variables that may influence a man’s chance of developing prostate cancer have been discovered by researchers.

• Age – Men under the age of 40 are less likely to get prostate cancer than older men, although the risk increases significantly after age 50. Men older than 65 are affected by prostate cancer in about 6 out of 10 instances.
• Race/Ethnicity – African American and Caribbean men of African heritage are more likely than men of other races to acquire prostate cancer. These males tend to be younger when it does develop in them. Asian American and Hispanic/Latino men are less likely to develop prostate cancer than non-Hispanic white men. The reasons for these racial and ethnic differences are not universally understood.
• Geography – The regions with the highest rates of prostate cancer include North America, western Europe, Australia, and Caribbean islands. Less frequently seen in South America, Central America, Asia, and Africa. There is no apparent explanation for this. At least some of this discrepancy is presumably explained by more thorough prostate cancer screening in certain industrialized nations, but other elements, such as dietary and lifestyle variations, are also probably significant. For instance, Asian Americans are less likely to get prostate cancer than White Americans, but they are more likely to do so than Asian males of a comparable racial origin.
• Family background – It appears that prostate cancer runs in certain families, which implies that there may occasionally be a hereditary or genetic aspect at play. However, men with no history are most likely to develop prostate cancer. A man’s chance of developing prostate cancer is more than doubled if his father or brother has it (Males who have a sibling with the disease are more at risk than men who have a parent with the condition.) Men who have many relatives who have the disease are at notably increased risk, particularly if those relatives were young at the time the disease was identified.
• Gene alterations – Although several inherited gene alterations (mutations) appear to increase the chance of developing prostate cancer, they probably only account for a tiny portion of cases overall.
• Men’s chance of developing prostate cancer can be enhanced by inherited mutations of the BRCA1 or BRCA2 genes, which are associated with an elevated risk of breast and ovarian cancers in a few families (especially mutations in BRCA2).
• Prostate cancer risk is generally higher in men who have Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), a disorder that is brought on by inherited gene alterations.
• The risk of prostate cancer in men can also be increased by other hereditary gene alterations.

About Prostate Cancer:

• Prostate cancer is one of the most common forms of cancer. Many prostate cancers are slow-growing and confined in the prostate gland, where they may not cause much harm.
• Although some prostate cancers spread slowly and may require little to no therapy, others are aggressive and can spread very fast. Early-stage prostate cancer that is still contained to the prostate gland provides the greatest prognosis for recovery.
• The second most prevalent cancer among males to be diagnosed is prostate cancer. About half of all men with cancer will eventually get metastatic cancer after their initial diagnosis.
• However, a tiny number of men experience a deadly, metastatic form of the disease much sooner after diagnosis.
• Metastasis typically takes 15 or more years to develop. Clinicians might start more aggressive therapies sooner by identifying people who might go on to acquire this kind of prostate cancer in the early stages. The most recent research was released in the journal Clinical and Translational Medicine.

One of the longest and most thorough molecular studies on the development of prostate cancer is this one. The biology of the illness is difficult to study because of how slowly it develops.

The researchers were able to analyse the samples from 185 men who had their prostates removed after being diagnosed with prostate cancer in the 1990s and 2000s because of the bank of biopsies that has been kept at Garvan and St. Vincent’s Hospital for the past 20 years. The researchers then monitored the number of individuals who recovered and the number who died from the condition, some more than 15 years later. The researchers looked at their genomes and discovered 1420 locations that were unique to prostate cancer and where epigenetic changes, or DNA methylation marks, may be seen. The methylation process can alter a gene’s function without altering the gene’s DNA sequence, as a mutation does.

The CACNA2D4 gene, which is involved in calcium channel modulation, was found to be a significant biomarker in 18 of those sites. Researchers urgently need to comprehend how the methylation process may decrease the gene’s function because there is very little information available about this gene and it is not frequently profiled, according to Dr. Ruth Pidsley, the study’s first author. The group has made the detailed epigenome sequencing data accessible for the use, by other researchers in their work on prostate cancer. The results of the epigenome study revealed variations between individuals with the fatal and non-lethal types of prostate cancer, and the biomarkers also increased the prognostic accuracy of currently used clinical tools.

The new discoveries provide promise for a technique to treat cancer in a more individualized manner. According to Professor Lisa Horvath, an oncologist and researcher at Garvan who served as the clinical lead on the study, what we really want to know on the day a patient is diagnosed is who has the potential for lethal prostate cancer and who does not because it will change the way the cancer is treated.

Researchers may be able to determine who has deadly prostate cancer and who does not use these epigenetic biomarkers. The next step is to expand the research and find out if the biomarkers may initially be found in blood samples.

Reference:

• https://onlinelibrary.wiley.com/doi/10.1002/ctm2.1030
• https://www.mayoclinic.org/diseases-conditions/prostate-cancer/symptoms-causes/syc-20353087
• https://www.cancer.org/cancer/prostate-cancer/about/what-is-prostate-cancer.html