An international study led by researchers from Mayo Clinic has identified a genetic factor that may explain why some patients with colorectal cancer that has spread to the liver suffer more severe liver damage after chemotherapy. For patients with colorectal liver metastases, surgery offers the best chance of long-term survival. To improve outcomes, many patients receive chemotherapy before surgery. Although this approach can shrink tumors and make them more operable, a potential side effect is liver injury. Researchers analyzed liver health tests to check how chemotherapy affected liver function and genetic markers already linked to liver diseases in other contexts. They found that a specific variant of the PNPLA3 gene, known to affect fat metabolism in the liver, was strongly associated with liver injury after chemotherapy. Patients with two copies of this variant were especially vulnerable, and all of them developed signs of significant liver injury after chemotherapy. According to Dr. Starlinger, the PNPLA3 variant is common worldwide, but its prevalence varies by population. For example, in Japan, the mutation is present in over 41% of the population. These findings suggest that a blood test to check for the PNPLA3 variant, along with monitoring liver health, can help doctors identify patients at highest risk of liver damage from chemotherapy. "These findings give us insight into how we can adjust treatment strategies to better manage care for patients diagnosed with colorectal liver metastases while potentially avoiding a negative side effect of chemotherapy," says Dr. Starlinger. "Chemotherapy can still be a suitable treatment option; with this information, we can personalize treatment for each patient, for example, by adjusting chemotherapy or allowing more time for the liver to recover before surgery."
