Prostate cancer is not a cookie-cutter disease; it’s different in every man because of distinct genetic, immune, and environmental factors. But it’s even more complicated than we knew, and the solution requires precision medicine. In prostate cancer, there is no “one size fits all” treatment, and the reason is that many factors play a role in the development of the disease, and in its diagnosis and treatment.
At the most basic level, these factors fall into two very broad categories. Briefly, they are:
Genetic/Ancestral Factors
Over the last two decades, scientists have found some key gene mutations that make a man more likely to develop prostate cancer. Some of these are inherited, and some happen over the course of a lifetime, mostly likely influenced by diet and lifestyle. But it may be that scientists have barely scratched the genetic surface: That’s because the genes known to play a role in prostate cancer, the biomarkers used to detect and monitor prostate cancer, and the responses to various forms of treatment – all these discoveries – have been studied mainly in Caucasian men.
Might other genes might be involved in men of different races? Undoubtedly. For example: Research by PCF-funded scientists and others has shown different genetic mutations, biomarkers, and treatment responses in Black men, who are at higher risk compared to other men of developing aggressive prostate cancer.
Most likely, Latino/Hispanic men, Native American men, and Asian American/Pacific Islander men also have unique genetic cancer profiles – but we don’t know what they are, because these populations have been under-represented in most studies. “The genomic studies in prostate cancer that we have are highly Eurocentric,” explains radiation oncologist Brandon Mahal, M.D., a physician-scientist at the University of Miami’s Miller School of Medicine-Sylvester Comprehensive Cancer Center. “Over 90 percent of cancer (mutated gene) sites have been discovered in European populations. When you don’t study broad groups, when you develop genomic risk scores and treatments that are really only designed for one population, that may not be as generally applicable.”
Furthermore: even within racial/ethnic groups, there are subgroups at higher risk, Mahal adds. “Race is a loaded social construct that includes a lot of the social determinants of health – such as income, education, and health literacy – and also ancestral risks.” Among Black men, men with West African ancestry have a higher risk of developing prostate cancer “regardless of where they live, their diet, or their socioeconomic status; and they have a higher risk of dying from prostate cancer.”
There are also epigenomic changes – small genetic alterations that may not cause cancer by themselves, but when added up can make a more favorable environment in which cancer can develop. This brings us to the second very broad category:
Environmental Factors
What can cause epigenomic changes? Stress can do it. So can sleep deprivation and lack of exercise. So can a poor diet. So, in fact, can the typical Western diet – high in fat and carbs, low in fruits and vegetables. “America is an interesting case study with this,” says Mahal. “People come here from all different parts of the world, and their cancer risk changes when they start eating the Western diet” – or, in the case of Native Americans, eat Western foods instead of the traditional diet.
And then there are socioeconomic barriers to health. Mahal is working to address these disparities on a national level, as a member of the White House Health Equity Roundtable. In prostate cancer, says Mahal, “for basically all racial/ethnic minority groups, there tend to be lower rates of treatment when indicated, less guideline-appropriate care, lower rates of screening, increased risks of lower-quality care, and more adverse outcomes.”
Native Americans: “There are lower screening rates for prostate cancer, and for all other cancers in Native American populations. There’s lower access to high-level care – care at tertiary centers where all treatments are available, including clinical trials. Much of the disparity that we see is driven by geographic location, isolation, poverty, and lack of access to centers that would provide screening and care. These are structural barriers; the medical literature has started referring to this as structural racism.”
One structural barrier is the phenomenon of “food deserts,” regions or neighborhoods that might have available fast food or street food, but no or few stores offering fresh produce or lower-calorie, nutrient-rich, prepared food. A poor diet can lead to obesity, which increases the risk of diabetes and heart disease, and also increases inflammation – which, in turn, can raise the risk of prostate cancer.
“It’s genomics 2.0,” says Mahal. “There are risk factors for prostate cancer, risk factors that drive disparities in prostate cancer, and ultimately, risk factors that drive gene/environment interactions. We ought to be studying prostate cancer through the lens of disparities, so we can better understand why populations are at different risks, and understand more about cancer risks in general. We are in the early, early innings.”
Asian Americans and Pacific Islanders (AAPI): The AAPI umbrella group covers a huge mix of populations, including people from China, Japan, Korea, the Pacific Islands, Vietnam, the Philippines, and elsewhere. Their prostate cancer risks are not the same. “Chinese Americans tend to have a lower risk of developing prostate cancer and of dying from it,” says Mahal. “However, individuals from the Pacific Islands, Vietnam and the Philippines tend to have lower screening rates, a higher risk of developing prostate cancer, and more aggressive disease.”
Latinos/Hispanics: Here’s another broad umbrella term covering a great amount of diversity – including people who came from Mexico, the Caribbean, Cuba, Haiti, the Dominican Republic, Puerto Rico and elsewhere. In Miami and south Florida, where Mahal is, “the genetic ancestry is not homogenous at all. There is a wide variation in risk factors, including varying degrees of West African ancestry. That being said, Latinos as a group are at an increased risk of receiving inferior care, are more likely not to receive treatment when indicated, are less likely to undergo screening and diagnostic tests, and more likely to be diagnosed with more advanced disease. In South Florida, Latino men are presenting with higher Gleason grade disease and more metastatic disease. Ultimately, Latino men are found to have overall worse outcomes when diagnosed with prostate cancer, and a lot of that has been attributed to differences in quality of care and access to care.”
So: Are these men presenting with worse disease because they are more genetically predisposed to aggressive disease, or is it that their prostate cancer was not detected at an earlier, more curable stage? Or are there other socioeconomic impacts of structural barriers? Maybe it’s all of the above. Mahal believes the best way to change outcomes is direct engagement to raise awareness, to promote screening and encourage early treatment at the community level. “In South Florida, we’ve been characterizing the burden of prostate cancer across 102 neighborhoods, and what we have seen is that areas where there’s a high risk of developing and dying of prostate cancer also tend to be areas where there are low PSA screening rates. We are actively working to educate the community on a neighborhood level,” using specially equipped vehicles that Mahal describes as “game-changers” to take PSA screening directly to residents. “We’re hoping to track the impact of better PSA screening across multiple risk factors, with basic and clinical research.” It will take time to gauge the results of this outreach, but “we’re committed to saving lives from prostate cancer, so we are in this for the long haul.”
