A genetic profile may help doctors evaluate a patient’s susceptibility to radiation-induced breast cancer, according to results from a study published in Blood.1 The study identified 9 genetic variants associated with subsequent breast cancer following radiation therapy for Hodgkin lymphoma (HL), and the authors used these 9 loci to calculate a polygenic risk score that could help improve clinical decision making for patients with HL.

Survivors of HL have about 6-fold risk of developing breast cancer compared with the general population. Because HL often strikes in early adulthood, and survival rates are high, these patients may have a long life ahead of them in which to develop a second primary cancer. In addition, HL is often treated with chest radiation. This can have a more severe impact on younger patients, whose breasts are still developing.

Led by Flora van Leeuwen, PhD, of the Netherlands Cancer Institute, the team wanted to home in on genes that specifically increase susceptibility to radiation-induced breast cancer. To do this, they carefully designed the study to avoid turning up genetic variants that predisposed an individual to breast cancer in general.

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“In terms of epidemiologic study design, it’s really well done,” said James Allan, MD, professor of Cancer Genetics at the Northern Institute for Cancer Research in Newcastle Upon Tyne, U.K. He explained further: “Very few [studies] have gone to these lengths in terms of their control selection.”

The gene search incorporated 2 phases. First, they compared breast cancer patients previously treated for HL with patients whose breast cancer was their first primary cancer. They matched the cases by age, country, and year of diagnosis. This step helped separate breast cancer susceptibility genes from genes specific to radiation susceptibility.

In the second phase, they compared 2 groups of HL survivors: those who developed breast cancer and those who did not. They matched these individuals by time elapsed after HL treatment, so a case whose breast cancer came on 8 years after their lymphoma would be matched with a control who survived 8 years without getting breast cancer. In this way, the contribution of variants associated with HL risk should be minimized.