Association of Vitamin B12 Deficiency with Tumor Marker Variability and Metabolic Parameters in Non-Malignant Conditions

Background/Objectives: Vitamin B12 (cobalamin) plays an essential role in DNA synthesis, erythropoiesis, and cellular metabolism. Its deficiency is common in the general population and may influence various biochemical markers. Tumor markers such as CA 125, CA 15-3, CA 19-9, CEA, and AFP are widely used in oncology, yet their levels can also be affected by non-malignant conditions. This study aimed to investigate the relationship between serum vitamin B12 levels and tumor marker concentrations in non-cancerous patients. Methods: This retrospective study included 250 adult participants (141 with low serum vitamin B12 < 200 ng/L and 109 with normal B12 ≥ 200 ng/L) who presented to Etlik City Hospital between June 2022 and June 2025. All participants were non-smokers and had no history of chronic kidney disease or malignancy. Hematologic, biochemical, thyroid, and iron parameters were analyzed alongside tumor markers (CA 15-3, CA 125, CA 19-9, CEA, and AFP) using standard immunoassay techniques. Statistical analyses included group comparisons, correlation testing, and logistic regression to identify factors independently associated with low vitamin B12 levels. Results: Patients with low vitamin B12 levels exhibited significantly lower hemoglobin, hematocrit, white blood cell, and neutrophil counts (p < 0.01 for all). Free T4 and serum iron were independently associated with low B12 levels in multivariable analysis (p < 0.001). Among tumor markers, CA 125 and CEA were significantly reduced in patients with vitamin B12 deficiency (p < 0.0001), while CA 15-3 showed a moderate inverse correlation with B12 concentration (r = –0.36, p < 0.0001). Conclusions: Vitamin B12 deficiency is associated with alterations in hematologic, thyroid, and iron parameters and may be associated with serum tumor marker levels even in non-cancerous individuals. Recognizing the potential association between B12 status and tumor marker variability may contribute to more cautious interpretation of tumor marker results in clinical practice.