Abstract
Simple SummaryVitamin D3 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 D3 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 D3 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 D3 and higher homocysteine level. Based on our results, we recommend a modified vitamin D3 supplementation regimen for metastatic CRC, which includes laboratory measurement-based titration.Background: 1α,25-dihydroxycholecalciferol (1,25(OH)2D3) 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)2D3 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 D3 supplementation (ND vs. D). Results: 1,25(OH)2D3 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)2D3 (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)2D3 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 D3 supplementation and better management of comorbidities are recommended for CRC.
Highlights
Colorectal cancer (CRC) is the third most commonly diagnosed cancer type with almost1.9 million new CRC cases being discovered worldwide annually, and CRC is responsible for 916,000 deaths, being the second leading cause of cancer deaths, according to the GLOBOCAN 2020 data [1]
The patients were divided into four cohorts based on the presence of metastases and whether they were on vitamin D3 supplementation during our observation time or not
Twenty-five, ten, and thirty-two patients were assigned to the ‘adjuvant without vitamin D3 supplementation’ (Adj-ND), ‘adjuvant with vitamin D3 supplementation’ (Adj-D), ‘metastatic without vitamin D3 supplementation’ (Met-ND), and to the ‘metastatic with vitamin D3 supplementation’ (Met-D) groups, respectively
Summary
Colorectal cancer (CRC) is the third most commonly diagnosed cancer type with almost. A large number of observational and randomized clinical trials have investigated the effect of vitamin D on CRC and associations have been proposed between the circulating levels of vitamin D metabolites, CRC incidence, and patient survival [5,6,7,8]. Despite the large and increasing number of studies investigating vitamin D3 or homocysteine in CRC, to our knowledge, no study investigated the single-time nor the longitudinal relationships between serum 1,25(OH)2D3 and homocysteine levels in CRC, nor if their changes are affected by any other laboratory or clinicopathological parameters. A retrospective longitudinal observational cohort study was created to investigate the combined effect of vitamin 1,25(OH)2D3 and homocysteine on CRC. The possible associations between the two parameters and the various clinicopathological properties, comorbidities, other laboratory measurements, and the anamnestic data were further objectives of the investigation
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