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Personalizing CA125 Levels Using Tumor Marker Variants: A Case-Control Analysis of Diagnostic Performance for
Yuto Hozaka1, Anne Macgregor-Das1, Masataka Hayashi1
1Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University, Baltimore, Maryland.
Summary
Genetic variants can personalize Cancer Antigen 125 (CA125) levels, creating tailored reference ranges. However, this approach did not significantly enhance CA125
Area of Science:
- Biochemistry
- Genetics
- Oncology
Background:
- Cancer Antigen 125 (CA125) is a key biomarker for monitoring ovarian and other cancers.
- Previous studies identified genetic variants influencing CA125 levels.
- The utility of stratifying CA125 by these variants was explored.
Purpose of the Study:
- To evaluate the diagnostic performance of CA125 in pancreatic ductal adenocarcinoma (PDAC).
- To assess if stratifying CA125 levels by genetic variants improves diagnostic accuracy.
- To investigate personalized CA125 reference ranges based on genetic profiles.
Main Methods:
- CA125 levels were measured in 807 controls and 450 PDAC patients.
- Genotyping was performed for 10 variants across four genes (GAL3ST2, MSLN, D2HGDH, MUC16).
- CA125 levels were compared across variant groups, and personalized cutoffs were established.
Main Results:
- Six variants were used to categorize controls into four groups, with mean CA125 levels varying up to fourfold.
- African Americans showed a higher prevalence of variants associated with lower CA125 levels.
- Personalized CA125 cutoffs did not significantly improve PDAC diagnostic sensitivity or specificity compared to uniform cutoffs (AUC 0.702 vs. 0.700).
Conclusions:
- Genetic variants can inform personalized CA125 reference ranges.
- This personalization strategy did not enhance diagnostic performance for pancreatic cancer.
- Further evaluation in other cancers, like ovarian cancer, is warranted.
