September is Prostate Cancer Awareness Month. Many of you know breast cancer firsthand, but you may be surprised by some of the connections between breast and prostate cancer. About one in eight men will be diagnosed with it during his lifetime,1 making it one of the most common cancers among men.
Breast and prostate cancer also have some important things in common. Both may be influenced by hormones, both may be treated with radiation, and both can be connected to inherited genetics. For example, men who carry certain inherited gene changes in the BRCA2 gene, which many people associate with breast cancer, also have a higher risk of developing prostate cancer.
This fall, our research team presented four studies at the annual meeting of the American Society for Radiation Oncology (ASTRO), the world’s largest gathering of doctors and scientists who treat cancer with radiation. All four studies explore a question that matters to anyone who has received radiation therapy or is considering having radiation therapy—why do some people experience serious side effects while others have few or none? And can we know ahead of time who is most likely to be affected?
What our genetics can tell us about radiation side effects
Many of you know MiraKind for our work on the KRAS-variant and other unique inherited genetic markers. These are microRNA variants—small genetic differences that can affect how genes are regulated and may influence how our bodies respond to cancer treatment.
Here’s what that means. Every one of us is born with small, natural differences in our DNA. Some of those differences affect microRNAs, tiny molecules that act like “dimmer switches” to turn other genes up or down. When a small change in DNA affects how a microRNA works, we call it a microRNA variant. All four studies we’re presenting at ASTRO are built on the same kind of microRNA variant that the KRAS-variant comes from—the family of inherited markers that MiraKind has studied for years. The prostate cancer test, the laboratory study, and the head and neck cancer study all build on the same idea: these inherited “dimmer switch” differences may help explain why people respond so differently to treatment.
Like the KRAS-variant, these markers can be found with a simple cheek swab. Because you are born with these genetic differences, they don’t change over time, so they can be checked before treatment, when the information is most useful.
Study 1: A test that helps prevent urinary problems
Many men with prostate cancer now receive a short, intensive course of radiation called SBRT. It works very well and is convenient. However, some men develop urinary problems months or years later, such as urgency, frequent trips to the bathroom, discomfort, or bleeding.
We helped develop a test called PROSTOX Ultra to identify men at higher risk for these problems. The test looks at a group of microRNA variants. In this study, we asked two questions: does the test really work, and does knowing the result really help?
In a trial of 208 men, doctors received each man’s test result before treatment. Men who tested as “high-risk” of having side effects from SBRT were offered a somewhat longer radiation schedule for treatment. Among high-risk men who chose the longer schedule, none of the 13 developed significant urinary problems. But among high-risk men who opted to receive SBRT, about three out of four developed side effects. Overall, significant urinary problems in the trial dropped to about 18%, which included the high-risk men who opted to do SBRT, compared with roughly a historical rate of 32% in men not tested for PROSTOX Ultra.
We then combined results from four clinical trials in the United States, Canada, and the United Kingdom, covering 457 men who were followed for about five years. Men who tested high-risk for side effects and received SBRT developed significant urinary problems about 81% of the time, compared with about 15% for men who tested low-risk.
What it means: A simple test before treatment can help men and their doctors choose the radiation approach most likely to protect their quality of life.
Study 2: Adjusting the test for men who have already had surgery
Some men have their prostate removed and later need radiation to treat cancer cells that may still be in the area. We wanted to know whether PROSTOX Ultra could also predict side effects in these men, so we tested it using data from two clinical trials involving about 150 patients.
The same genetic markers used by PROSTOX Ultra were able to distinguish between men at lower and higher risk of side effects. However, the results needed to be interpreted somewhat differently for men who had already had surgery.
What it means: The same group of microRNA variants used in Study 1 may also help predict side effects for men receiving radiation after prostate surgery. The test just needs to be adjusted for this group of patients.
Study 3: Looking inside the cells to understand why
Understanding why a test works can give us greater confidence in what it tells us. So we grew cells in the laboratory from men with high-risk and low-risk PROSTOX results, exposed the cells to radiation, and watched how their genes responded over two days.
The cells from high-risk men behaved differently, both before and after radiation. Those differences involved important processes such as how cells repair damaged DNA and control when they divide.
What it means: People who are more sensitive to radiation may be born with cells that are “wired” to respond differently. This helps us understand why the PROSTOX test can identify people at greater risk of side effects and may eventually point to new ways to reduce that risk. It also shows how a small change in a microRNA “dimmer switch” can ripple out to affect many genes at once, something we have also seen in our KRAS-variant research.
Study 4: Beyond prostate cancer, with a link to BRCA2
Our fourth study looked at 171 patients with head and neck cancer who participated in a national clinical trial. These patients often receive radiation together with chemotherapy, which can cause serious short- and long-term side effects.
Our research found that combining genetic information with standard medical information did a better job of identifying patients at risk for serious side effects than medical information alone. The genetic information was also associated with differences in patient outcomes. Patients identified as high-risk had a median survival of about 2¼ years, compared with nearly 4½ years for those identified as low-risk.
One finding may be familiar to our readers. The genetic marker most strongly associated with late side effects was a microRNA variant found in the BRCA2 gene. This was not one of the BRCA2 mutations associated with hereditary breast and ovarian cancer. In this study, the variant was associated with a lower risk of developing late side effects.
What it means: MicroRNA variant-based inherited genetics may help us better understand how people with different types of cancer respond to treatment. With more research, this information could potentially help identify people at greater risk for serious side effects before treatment begins.
The bigger picture
When MiraKind began studying microRNA variants, the focus was mainly on understanding who might be at higher risk of developing cancer. Today, we’re learning that these same genetic markers can tell us much more. They can:
- predict who will have side effects from treatment
- guide doctors and patients toward safer treatment options
- help predict how well treatment will work.
Every person who has joined a MiraKind study has helped build the foundation for this work.
What you can do this month
- Encourage the men you love to talk with their doctors about prostate cancer screening. Most men should start this conversation around age 50. Black men and men with a family history of prostate, breast, or ovarian cancer should start earlier, often in their 40s.
- Share your family history. If breast cancer or a BRCA mutation runs in your family, the men in your family should know, because it can affect their prostate cancer risk too.
- If you or a loved one is facing radiation, ask about side effects. Talk with your care team about your individual risk of side effects and whether there are ways to better understand that risk before treatment begins.
Our goal has always been simple: to help every patient get the treatment that works best for them. We are grateful to the patients who took part in these trials and to all of you who support this work.
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