By simply looking at a short portion of a man's genome you can estimate the probability that he will die prostate cancer, even before getting sick, thanks to a massive genetic study conducted by RIKEN researchers. This ability will help detect cancer early in men who are at high risk of dying from it.
The results of research were published in the journal Nature Communications.
Prostate cancer: what are the chances of death?
Prostate cancer is the second most common cancer in men globally. It also has the highest heritability of all common non-skin cancers, indicating that a man's genetics play an important role in determining whether he will get cancer. This makes it an excellent candidate for genetic studies.
In many studies it is difficult to distinguish cause and effect. “The standard approach involves comparing samples from patients and healthy people,” says Chikashi Terao of the RIKEN Center for Integrative Medical Sciences. “But because the samples are obtained from patients after they have developed the disease, any differences between proteins or genes could be due to the presence of the disease.”
This is where genetic studies of inherited genetic variants come into play. “If we discovered differences in variants between people with prostate cancer and healthy people, these should be the causes and not the consequences, because those inherited variants should be different between the two groups even before developing the disease,” explains Terao.
Now, Terao and colleagues have applied the power of genetic studies to prostate cancer in a study involving data from 300,000 people.
The team focused on sites that bind the male hormone androgen because preliminary analysis revealed that variants of these sites play a dominant role in prostate cancer. They also assessed the risk of dying from prostate cancer rather than the risk of contracting the disease.
The results obtained indicated that the polygenic risk score developed in the study can be used to predict future risk of death from prostate cancer.
Furthermore, they showed that the androgen receptor-binding regions of normal prostate cells are particularly good at predicting this. “We found that about 40% of prostate cancer heritability can be traced to the 1% of the genome that encodes the androgen receptor binding site of the normal prostate,” says Terao.
Unlike many previous studies that focused on people of European descent, the study used data from Japanese people. “This enrichment was observed in both Japanese and Europeans, suggesting that the current findings can be generalized,” notes Terao.
The study's findings will help identify people at high risk early in life, who can then undergo testing more frequently throughout their lives.
A family history of cancer and genetic variants that may be inherited appear to be important risk factors for black men diagnosed with early-onset prostate cancer, a study involving Duke Health researchers has found.
Genetic studies usually recruit non-Hispanic white men, despite data showing that black men are disproportionately affected by prostate cancer and are more than twice as likely to die from the disease as their white counterparts.
Researchers have sought to address this health disparity by identifying genetic variants in black patients diagnosed with early-onset prostate cancer.
They sequenced the germline DNA of 743 black men diagnosed with prostate cancer at age 62 or younger. This is DNA found in male sperm, meaning it would contain genetic changes that could be passed on to a child.
The focus was on genes that repair DNA damage and on HOXB13, a gene that Cooney's research team found to be associated with hereditary prostate cancer in white men. The researchers identified 26 variants in 14 genes that could cause the disease among 30 men, about 4% of the patients studied.
We have completed the sequencing at Duke and our results reveal that men who had certain genetic variants were more likely to have a close relative diagnosed with cancer, had higher prostate specific antigen at the time of diagnosis, and had more severe cases,” he said. said Cooney.
“We need to take a closer look at genetic associations to learn more about black men's susceptibility to developing prostate cancer,” Cooney added. “This could potentially reduce health disparities.”
The reason for poor outcomes among black men diagnosed with prostate cancer includes both biological and social causes, such as access to health care. Data from a previous study reveals that genetic makeup may account for up to 40% of all prostate cancer cases.
“November is Men's Health Awareness Month, and our hope is that these findings will help Black men become more aware of their susceptibility to early-onset prostate cancer,” Cooney said. “If men know they have a family history of cancer, it's important to talk to a doctor and consider genetic testing. If they end up having a mutation, they are encouraged to undergo cancer screening earlier and more frequently.”
Other authors of the study include Matthew Trendowski, Christopher Sample, Tara Baird, Azita Sadeghpour, David Moon, Julie Ruterbusch, and Jennifer Beebe-Dimmer.
Researchers at the University of East Anglia have made an important discovery about how prostate cancer can start to develop. A new study published in Molecular Oncology reveals that the prostate as a whole, including cells that appear normal, is different in men with prostate cancer. This suggests that tissue cells throughout the prostate are primed and ready to develop prostate cancer.
This means that it may be better to treat the entire prostate rather than just the areas of the prostate affected by cancer. The team hopes their work can help scientists better understand the causes of prostate cancer and even prevent it altogether.
Lead researcher Professor Daniel Brewer, from UEA's Norwich Medical School, said: “Prostate cancer is the most common cancer in men, killing one man every 45 minutes in the UK.
“Often, when men are diagnosed with prostate cancer, clusters of cancer cells can be found in more than one location within the prostate. We wanted to know if this is due to changes in “nor
mal” prostate cells throughout the prostate.”
Cancer is caused by changes in DNA, the genetic code of life, that appear in every cell. The team studied the DNA code in 121 tissue samples from 37 men with and without prostate cancer.
Professor Brewer said: “The samples we studied included tissue from the cancer and tissue from other parts of the prostate, which look normal under the microscope.
“This produces a huge amount of data and, by applying a large amount of computer power, we can determine the differences that have occurred in the DNA, giving us an idea of how the cancer grows. We found that “normal” prostate cells in men who had prostate cancer had more mutations (changes in DNA) than “normal” prostate cells from men without prostate cancer.
“Based on the genetics of the analyzed samples, we created maps to understand where the different mutations occurred. And we showed that in most humans, mutations in normal cells are different from mutations in tumor cells.
“‘Normal’ prostate cells in men who have prostate cancer appear to provide a beneficial environment for prostate cancer cells to develop and grow. In other words, the entire prostate is primed and ready to develop prostate cancer driven by an as yet unknown, biological process.
“This work has improved our knowledge of how prostate cancer begins to develop and may one day give us clues about how to prevent or treat it. And it shows that it may be better to treat the entire prostate rather than just the areas of the prostate the prostate that has cancer,” she added.
Dr Hayley Luxton, Senior Research Impact Manager at Prostate Cancer UK, said: “This exciting new research shows for the first time how normal prostate cells can facilitate the growth and spread of prostate cancer.
“Researchers have found that normal prostate cells in men with prostate cancer have specific genetic changes that make them act like rich compost, providing the perfect environment for prostate cancer cells to grow and develop. These findings provide us with important new information about the early development of prostate cancer, which may one day give us clues about how to prevent it.”
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