High Genetic Risk for RA Not Linked to Radiation Toxicity

TOPLINE:

A recent analysis found that patients with a high genetic risk for rheumatoid arthritis (RA) do not face an increased risk for acute or late radiation-induced toxicities, suggesting no need to alter treatment plans based on RA genetic risk. 

METHODOLOGY:

• Having RA may increase patients’ risk for radiosensitivity, which could increase their risk for toxicities following radiotherapy. One explanation for this possible connection is that the genes linked to RA may overlap with those associated with radiosensitivity.
• Researchers analyzed patients with prostate cancer (n = 1494), lung cancer (n = 483), and breast cancer (n = 1840) from the REQUITE study cohort to assess whether those at a high genetic risk for RA also have an increased risk for radiotherapy toxicity. In other words, researchers investigated a potential link between a person’s underlying polygenic risk score for RA and risk for radiotherapy toxicities.
• The researchers monitored normal tissue toxicity prospectively for 2 years after radiotherapy. Acute toxicity was defined as the maximum reported toxicity within 3 months of radiotherapy; late toxicity was defined as the maximum reported toxicity from 3 months to 2 years after radiotherapy.
• Standardized total average toxicity scores were calculated, and 101 RA risk variants were evaluated to determine polygenic risk scores for patients treated with radiotherapy for prostate, breast, or lung cancer. 

TAKEAWAY:

• Higher RA polygenic risk scores were not associated with an overall increased risks for acute or late toxicities in any cohort.
• Looking at specific toxicities, individual acute or late toxicity endpoints were not significantly associated with polygenic risk scores in patients with breast cancer.
• In lung cancer, acute toxicities were not associated with polygenic risk scores. The risk for late esophagitis, however, was significantly higher for those in the top 10th percentile of polygenic risk score (though this finding was not validated in an independent cohort).
• For patients with prostate cancer, researchers did find an association between being in the top 10th percentile of weighted polygenic risk score for RA and the risk for acute rectal bleeding and late hematuria, but neither finding was validated in an independent cohort.

IN PRACTICE:

“Patients with a high genetic risk of [RA] do not appear to have an increased risk of normal tissue toxicity after receiving radiotherapy. These results suggest that radiotherapy planning and delivery does not need to be modified for these patients,” the authors concluded.

SOURCE:

The study, led by Alan McWilliam, PhD, Division of Cancer Sciences, University of Manchester, United Kingdom, was published online in the Journal of the National Cancer Institute.

LIMITATIONS:

Toxicity data were only available up to 2 years after radiotherapy; however, some radiation-induced toxicity can develop later. Additional variables beyond the preselected adjustment variables might have improved model performance. Furthermore, future studies should better account for dosimetric drivers of toxicity.

DISCLOSURES:

REQUITE received funding from the European Union’s Seventh Framework Programme. The authors reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.