The beauty of genome-wide association studies, points out epidemiologist Lindsay Morton, PhD, of the National Cancer Institute, is that “they give us the opportunity to look agnostically across the entire genome.” Rather than searching only candidate genes that are suspected to be involved, GWAS can turn up links to genes in unexpected pathways. These results must then be interpreted with caution, of course. “We don’t actually know from these studies alone which specific gene is really responsible for the effect we’re observing,” says Dr Morton. The polymorphisms serve as markers, but those genes may not necessarily have a functional role in the onset of cancer.

Dr Morton conducted a similar search for genetic variants associated with radiation-induced breast cancer risk among childhood cancer survivors.3 The variants uncovered by the 2 studies didn’t overlap, she said, because they used different genotyping arrays. Now, the groups are teaming up. “One of the most important things in this research area is international collaboration,” added Dr Morton. “We need larger numbers of patients in order to make reliable discoveries and generate reliable risk estimates that would be needed to translate the findings into the clinic.”

Exactly how clinicians would use this type of genetic testing remains to be seen, however. “The study’s really important, because it’s known that people getting chest radiation are at higher risk for breast cancer,” said Thomas Slavin, MD, medical geneticist at City of Hope, Duarte, California. He says the PRS could help ensure each patient gets the appropriate follow-up screening, as some need more than others. However, “it probably wouldn’t be used to pick people who are good radiation candidates — that’s probably a moot point,” he said. “If people are getting chest wall radiation, they’re getting it to save their life.”

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Jean Wright, MD, director of the Breast Radiation Oncology at Johns Hopkins University, Baltimore, Maryland, pointed out that treatments for HL have improved considerably through the years. “Going back decades, patients were treated with radiation alone,” she said. “Now, in the modern era, there’s a spectrum, and we have a lot of chemotherapy drugs.” For patients that still do require radiation, she says, “we make much more significant effort to avoid the breast tissue,” both because doctors are more aware of the risks and because the technology allows more focused treatment than it used to. These improvements, she says, are hopefully already lowering patients’ risks of later breast cancer.

“This wouldn’t by itself make a major change in clinical management,” said Dr Wright. “If I got this report and I saw that [a patient] had a low-risk profile, I still don’t think I’m going to [tell that patient they] don’t need heightened surveillance.”

Disclosure: Some of the study authors disclosed financial relationships with various companies and health systems. For a full list of disclosures, see the original study.

References

  1. Opstal-van Winden AWJ, de Haan HG, Hauptmann M, et al. Genetic susceptibility to radiation-induced breast cancer after Hodgkin lymphoma. Blood. 2019;133(10):1130-1139.
  2. Allan JM. Genetic susceptibility to breast cancer in lymphoma survivors. Blood. 2019;133(10):1004-1006.
  3. Morton LM, Sampson JN, Armstrong GT, et al. Genome-wide association study to identify susceptibility loci that modify radiation-related risk for breast cancer after childhood cancer. J Natl Cancer Inst. 2017;109(11):djx058.