Retrospective Analysis Highlights Disparities in Germline Testing in Prostate Cancer


Carrie Horton, MS, CGC, discusses how the findings from a retrospective analysis of germline testing rates among racially diverse groups of men with prostate cancer will guide future research and influence the steps community oncologists can take to increase testing rates.

Widening disparities in genetically informed cancer care prompted investigators to conduct a study of germline testing (GT) rates among racially diverse groups of men with prostate cancer, which highlighted the importance of GT in prostate cancer treatment.

A retrospective analysis of patients used the 14-gene prostate cancer panel to evaluate 427 men: African American (n = 237; 56%) and White (n = 190; 44%). The overall pathogenic/likely pathogenic (P/LP) variant rate was 8.2%.

Lower P/PL variant rates were reported among African American men (5.91%) vs White men (11.05%; P = .05). Further, rates of variants of uncertain significance (VUS) were 25.32% vs 16.32%, respectively (P = .02). Multiple VUSs were reported among 5.1% and 0.53% individuals, respectively (P =.008).1

“The idea is to not shy away from identifying the disparities. I think in the past there has been a stigma, but we can't solve the problem by not looking at it” said Carrie Horton, MS, CGC. “It’s been exciting to see Ambry [Genetics] rally behind a lot of health disparity research and I hope it can motivate other groups to do the same thing.”

In an interview with OncologyLive®, Horton, a senior clinical research specialist who designs and conducts studies at Ambry Genetics, discussed how the findings of the retrospective analysis of genetic testing in prostate cancer care will guide future research and influence the steps community oncologists can take to increase testing rates.

What was the catalyst for this investigation?

This specific study came about when the lead principal investigator Veda Giri, MD, a medical oncologist at Thomas Jefferson University Hospital, approached [Ambry Genetics]. She had seen a paper that we had done previously looking at the genetic testing results in individuals with prostate cancer, but it wasn’t selected for any one race or ethnicity. Since African Americans are more likely to develop and die of prostate cancer, there’s a real area of opportunity for targeted therapeutics in that group. Therefore the need for accurate genetic testing is even more important.

[Giri] came to us and wanted to see if we could use our existing data set and design a protocol with the intent to evaluate disparities between African American males with prostate cancer and White males. In doing that, we enriched our cohort for African Americans so that our sample was about equal. In most of the past studies looking at genetic testing in prostate cancer, identifying these disparities was a byproduct and not the whole focus of the study; there were a lot of inconsistencies [such as] the genes tested, not every [individual] had prostate cancer, or only 10% of the population was African American and 90% were other ethnicities. This study was specifically to evaluate the differences we’re seeing in genetic testing results in African Americans compared with White males.

We were excited to be able to help Giri with this because we have such a huge data set which is one of the benefits of working with Ambry [Genetics]; we can leverage that volume to find meaningful results.

What methods were used throughout the study?

We had our existing data set results of genetic testing in White males with prostate cancer from 2016 to 2017 and [all individuals] had the same multigene panel test—a 14-gene panel targeted for hereditary prostate cancer. We had the population needed for White individuals but wanted to make sure that we enriched for African Americans as well, so we expanded our timeline and our recruitment for African Americans through 2020.

We also looked at personal history and reviewed the clinic notes that were provided, [such as] pathology [reports] to see if there were any differences in when [individuals] were being sent for testing. [For example,] we wanted to see if African Americans were being sent only when they were extremely high risk but didn’t find a huge difference in who was being sent for testing in terms of the severity of the presentation. However, we saw a stark difference in the positive and VUS rates, where White individuals were almost twice as likely to have a positive result compared with African Americans. The VUS rate was half in White individuals compared with African Americans.

Was there anything particularly surprising in the findings?

There’s been precedent that we see a higher VUS rate in underrepresented populations across most genetic testing indications. However, one thing that was fairly novel [in this study] was that we found approximately half the positive findings in genes exclusive to White individuals. We need to improve our interpretation of the existing variants, and the fact that half the genes were exclusive to White individuals signals to me that perhaps there’s some room to improve our gene discovery.

We may not have found all the predisposition risk genes for prostate cancer in African Americans yet; there’s 2 genes where the positive rate is driven by a single mutation in White individuals. So, maybe there is a gene that has a mutation in an underrepresented group, and we just haven’t been able to find it because that’s not who has historically been presented for testing.

What effect can these data have for the testing moving forward? What action steps would you like to relay to your colleagues to take to help address these disparities?

There’s a shift now into focusing on identifying disparities and when we set out to shine a spotlight on the inequities, it allows us to figure out what’s really going on and provides an opportunity to improve and mitigate those disparities. I’m hoping this helps motivate [individuals] to revisit the idea of gene discovery in diverse populations and to come up with new ways for varying interpretation that are agnostic of race and ethnicity, that don’t rely on volume in order to accurately interpret variants. The more accurate we can get a test, especially in the hereditary prostate cancer space, the more opportunities there are for targeted medicine for PARP inhibitors such as olaparib [Lynparza].

It’s a multi-level [issue]. At the base level, we must] try to come up with better ways to engage underrepresented communities in genetic testing. We’ve seen studies that showed that underrepresented groups are preferred for genetic testing and adopt genetic testing at lower rates. [Solutions may include] looking more at genetic testing recruitment through nontraditional settings, such as health fairs or community gatherings. We first need to get [individuals] in the door to even get their result.

A more diverse population improves the accuracy that we can interpret the results with both in reference population databases, but also in the clinical and research cohorts. For laboratorians, I would encourage them to look at health disparities and what to do to circumvent existing gaps in evidence. For example, there are newer ways to derive functional evidence that does not rely on the accumulation of observing a variant multiple times.


Giri VN, Hartman R, Pritzlaff M, Horton C, Keith SW. Germline variant spectrum among African American men undergoing prostate cancer germline testing: need for equity in genetic testing. JCO JCO Precis Oncol. 2022;6(1):e2200234. doi:10.1200/PO.22.00234

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