When it comes to lethal prostate cancer, men of African descent are born with a genetic Achilles heel – or more likely, several points of weakness that make them vulnerable. It’s not all genetic; the deck is stacked against these men for many reasons, including the high-fat, low-vegetable Western diet, obesity, smoking, Vitamin D levels, and access to good medical care and early screening. But those are just the proverbial tip of the iceberg. The real threat is hidden deep in the genes.
Scientists like Kosj Yamoah, M.D., Ph.D., at the Moffitt Cancer Center, are at the forefront of navigating this treacherous iceberg, and discovering promising new ways to protect these men from it. With funding from the Prostate Cancer Foundation and the Department of Defense, Yamoah is looking at specific genes in African-American men that make prostate cancer aggressive, difficult to treat, and more likely to come back after treatment. Some of his pioneering work is being done with urologist Edward Schaeffer, M.D., Ph.D., Chairman of Urology at Northwestern.
“I’m focusing on the molecular issues that govern the disparity of outcomes between African-American men and other men,” says Yamoah, “trying to understand why these men by and large have a greater incidence of prostate cancer and are twice as likely to die from it. In this era of personalized medicine, we need to understand the biology of the disease – the genomic information that will help us predict which men will have more aggressive disease and worse outcomes.”
This work in a very specific population is going to have widespread effects – for all men with prostate cancer, and maybe even for men and women with other types of cancer, as well. “When you look at the mechanisms of the very worst forms of a disease, you can learn more about how that disease works in everybody,” says oncologist Jonathan Simons, M.D., CEO of the Prostate Cancer Foundation.
There are many genetic roads that lead to prostate cancer; many genes that can malfunction and throw off the body’s normal safety mechanisms that either keep cancer from starting at all or, once it starts, from getting worse and spreading. Some of these genes, such as BRCA1 and BRCA2, you may have heard of. Mutations in these genes make women more susceptible to breast or ovarian cancer, and men more vulnerable to prostate cancer. Others are not so famous, and are confusing for most of us to keep track of, because they all have alphabet-soup names.
Some genes are regulated by male hormones such as testosterone; others work like Miracle Gro – they make cancer cells thrive. The very worst work like lighter fluid, with cancer as the match; some of them knock out more helpful genes that function as fire retardant. Some genes, not particularly bad on their own, fuse together to make a genetic marriage from hell, and allow prostate cancer to spread.
What scientists didn’t realize was that the genes that do all this damage are not the same in everybody. Some genes only target black men.
In a landmark paper published in September 2015 in the Journal of Clinical Oncology, Schaeffer, Yamoah and colleagues identified a lethal half-dozen genes that seem to discriminate against men of African descent. The worst of them is called NKX3-1, and the exciting promise of these findings is that it will almost certainly be possible to develop a quick test to find out whether men have this bad gene – during regular prostate cancer screening, or even years before they develop prostate cancer.
What Yamoah, Schaeffer and colleagues have proven indisputably is that the molecular landscape of prostate cancer in men of African Ancestry is different. This also means that the molecular biomarkers that have shown promise in Caucasian men may not be that helpful in black men, because their molecular subtypes – basically, their particular set of genetic risks – are different.
“We have also identified subpopulations of African-American men who actually have an even higher risk of aggressive cancer.” This finding is very important: the scientists have discovered that having ancestors who came from Africa is one thing; where they came from in Africa is another. There are significant variations in prostate cancer in black men. “It turns out that the most aggressive prostate cancers come from West Africa, Jamaica, and the Bahamas.”
Many studies looking at the genetics of prostate cancer have never looked at the genetics of African ancestry. This means that in prostate cancer, genetics matter, race matters – but where your ancestors came from, and how much of that genetic material you have, really matters.
Note: Some men who consider themselves white have African ancestry somewhere in their past, too – which means they are at risk of having these same genes that make them more susceptible to prostate cancer, and to having an aggressive form of the disease. This is why it is important to know your family history.