Genetic testing before chemotherapy can significantly reduce severe side effects in patients with gastrointestinal (GI) cancers, according to new research from the Perelman School of Medicine at the University of Pennsylvania.
The study, published in JCO Precision Oncology, highlights how screening for genetic variants in two specific genes—DPYD and UGT1A1—can help personalize chemotherapy dosing, ultimately improving safety and outcomes for patients with cancers such as colorectal and pancreatic.
Each year, nearly 290,000 Americans are diagnosed with GI cancers, with colorectal cancer ranking as the third most common cancer in the United States. Despite this prevalence, current chemotherapy protocols often rely on standard drug doses, which do not consider individual genetic differences in drug metabolism.
This one-size-fits-all approach can lead to serious, sometimes life-threatening reactions in patients who carry certain gene variants.
The Penn Medicine study examined how variations in the DPYD and UGT1A1 genes affect the body’s ability to process two widely used chemotherapy drugs: fluoropyrimidines and irinotecan. The DPYD gene produces an enzyme vital for breaking down fluoropyrimidines.
An estimated 5 to 8 percent of the population carries DPYD variants that impair this function, leading to dangerous drug accumulation and side effects such as suppressed blood cell production, mouth sores, or hand-foot syndrome.
Similarly, variations in the UGT1A1 gene slow the metabolism of irinotecan, heightening the risk of severe diarrhea and dangerously low white blood cell counts.
By identifying these variants through a simple blood test, clinicians can adjust doses appropriately, minimizing harm without compromising the effectiveness of treatment.
The study enrolled 517 patients across three University of Pennsylvania Health System sites, all of whom were beginning treatment with either fluoropyrimidines or irinotecan. Of these, 288 underwent genetic testing.
Sixteen patients tested positive for one of the variants and received reduced drug doses accordingly. Only 38% of them experienced severe side effects, compared to 65% of 17 biobank patients with the same variants who received standard doses without prior testing.
The benefits extended beyond side effect reduction. Among those who underwent testing, fewer required changes to treatment dosage and frequency (38% vs. 76%) or discontinued treatment altogether (31% vs. 47%).
These findings reinforce the promise of precision medicine—where genetic insight helps guide safer, more effective treatment strategies. The study was supported by the Penn Center for Precision Medicine and the National Institutes of Health’s National Center for Advancing Translational Sciences.
READ MORE
Western Diet and Sedentary Habits Fueling Rise in GI Cancers Among Young Adults
FDA Approves New Eye Drops to Help Adults See Up Close Better
mRNA Vaccine Technology: A Health Breakthrough Facing New Challenges
