The Interplay Between CA19-9 and the Lewis Blood Group System: Implications for the Diagnosis of Gallbladder Cancer

CA19-9 is one of the most widely applied tumor markers in clinical oncology, particularly in the diagnosis and prognostic evaluation of biliary tract and pancreatic cancers. However, its clinical utility is limited by biological variability, most notably the influence of the Lewis blood group system, which may result in false-negative findings. The Lewis system is composed of three major phenotypes, Le(a+b-), Le(a-b+), and Le(a-b-), with the less frequent Le(a+b+) also reported in certain populations. Current evidence indicates that CA19-9 expression occurs predominantly in Le(a+b-) or Le(a-b+) individuals, whereas it is largely absent in Le(a-b-) individuals. Insufficient consideration of this factor in clinical settings reduces diagnostic accuracy and complicates interpretation of CA19-9 results. This review summarizes the current understanding of the relationship between CA19-9 and the Lewis system, critically evaluates recent clinical studies, highlights existing limitations, and discusses the potential role of combined CA19-9 and Lewis typing in improving the diagnostic value of gallbladder cancer.