Longitudinal Analysis of 1α,25-dihidroxyvitamin D(3) and Homocysteine Changes in Colorectal Cancer

SIMPLE SUMMARY: Vitamin D(3) and homocysteine level abnormalities are both strongly related to colorectal cancer (CRC) etiology. The aim of this retrospective study was to investigate the longitudinal change in these two parameters and the relationships between the two, in addition with other clinicopathological and laboratory parameters. A swoosh-shaped trend was observed for the change in serum homocysteine levels of all of the CRC patients. The circulating vitamin D(3) level was constant or increased in those patients without metastasis. After an initial increase, the disease-worsening effect of metastases cancelled out all of the positive effects of vitamin D(3) in metastatic patients, even despite its continuous supplementation. Right-sided tumors, male sex, and the pathological values of serum lipids, albumin, total protein, and inflammatory markers were associated with lower vitamin D(3) and higher homocysteine level. Based on our results, we recommend a modified vitamin D(3) supplementation regimen for metastatic CRC, which includes laboratory measurement-based titration. ABSTRACT: Background: 1α,25-dihydroxycholecalciferol (1,25(OH)(2)D(3)) and homocysteine are known to play a role in the pathophysiology of colorectal cancer (CRC). In health, the two changes are inversely proportional to each other, but little is known about their combined effect in CRC. Methods: The serum 1,25(OH)(2)D(3) and the homocysteine levels of eighty-six CRC patients were measured, who were enrolled into four cohorts based on the presence of metastases (Adj vs. Met) and vitamin D(3) supplementation (ND vs. D). Results: 1,25(OH)(2)D(3) was constant (Adj-ND), increased significantly (Adj-D, p = 0.0261), decreased (Met-ND), or returned close to the baseline after an initial increase (Met-D). The longitudinal increase in 1,25(OH)(2)D(3) (HR: 0.9130, p = 0.0111) positively affected the overall survival in non-metastatic CRC, however, this effect was cancelled out in those with metastasis (p = 0.0107). The increase in homocysteine negatively affected both the overall (HR: 1.0940, p = 0.0067) and the progression-free survival (HR: 1.0845, p = 0.0073). Lower 1,25(OH)(2)D(3) and/or higher homocysteine level was characteristic for patients with higher serum lipids, albumin, total protein, white blood cell and platelet count, male sex, and right-sided tumors. No statistically justifiable connection was found between the target variables. Conclusions: A measurement-based titration of vitamin D(3) supplementation and better management of comorbidities are recommended for CRC.