ASO Author Reflections: Using a CA19-9 Tumor Marker Gene Test to Assess Outcome after Pancreatic Cancer Surgery

Excerpt

Traditionally, carbohydrate antigen 19-9 (CA19-9) levels have been the most widely used marker for assessing tumor burden and therapy response in pancreatic ductal adenocarcinoma (PDAC). However, the interpretability of CA19-9 is complicated by significant differences in an individual’s capacity to synthesize CA19-9, influenced by common variants in the FUT2 and FUT3 genes.¹ Individuals can be classified into four functional FUT groups, each with distinct CA19-9 normal reference ranges that provide a more personalized approach to evaluating CA19-9 levels in patients undergoing pancreatic surveillance.² These four groups are: (i) FUT3-null individuals (homozygous or compound heterozygous for non-functional FUT3 alleles) who comprise ~ 10% of the population; (ii) FUT-low individuals (one FUT3 null allele and at least one functional FUT2 allele, i.e., FUT2 intact) who comprise ~ 1/3 of the population; (iii) FUT intermediate individuals (functional FUT3 variants with intact FUT2) who also comprise ~ 1/3 of the population; or (iv) FUT-high individuals (homozygous null or compound heterozygous for a FUT2 null variant with at least one FUT3 functional allele) who comprise ~ 22% of the population. Mean levels of CA19-9 are significantly different for each group. For example, average levels in controls are almost three times higher in FUT-high compared with FUT-low individuals. The corresponding upper limit of the CA19-9 reference range for the four groups were 3, 35, 42, and 89 U/mL.² Our research investigates whether incorporating these genetic factors into a CA19-9 tumor marker gene test can enhance its prognostic value.³ …