Abstract
Current knowledge on the role of retinol in the prognosis of patients with colorectal cancer (CRC) is very limited. We investigated the association of serum retinol levels with survival outcomes in a large cohort of 2908 CRC patients from Germany. Retinol concentrations were determined in serum collected shortly after diagnosis by mass spectrometry. Associations between serum retinol levels and survival outcomes were assessed using multivariable Cox regression and dose-response analyses. The joint association of serum retinol and serum 25-hydroxyvitamin D3 (25(OH)D3) with survival outcomes was also examined. During a median follow-up of 4.8 years, 787 deaths occurred, 573 of which were due to CRC. Dose-response curves showed an inverse relationship between serum retinol levels and survival endpoints in the range of <2.4 µmol/L, but no associations at higher levels. Low (<1.2 µmol/L) versus high (≥2.4 µmol/L) serum retinol levels were associated with poorer overall survival (Hazard ratio (HR) = 1.46, 95% confidence interval (CI) = 1.19–1.78, P-trend = 0.0003) and CRC-specific survival (HR = 1.69, 95% CI = 1.33–2.15, P-trend < 0.0001). Joint presence of low serum retinol (<1.2 µmol/L) and low 25(OH)D3 (<30 nmol/L) was associated with a particularly strong decrease in overall and CRC-specific survival. Low serum retinol levels were identified as a predictor of poor survival in CRC patients, in particular when co-occurring with low serum concentrations of 25(OH)D3. The clinical implications of these findings require further investigation.
Highlights
Colorectal cancer (CRC) is the fourth most common cause of cancer mortality worldwide [1].in patients with established disease, the ascertainment of factors that may ameliorate their prognosis is highly needed.Nutrients 2018, 10, 510; doi:10.3390/nu10040510 www.mdpi.com/journal/nutrientsVitamin A is a nutrient obtained from the diet as either preformed vitamin A derived from animal products or provitamin A carotenoids (α-carotene, β-carotene, and β-cryptoxanthin) in colored vegetables [2]
This is the largest prospective study investigating the association between circulating retinol and survival outcomes in CRC patients, and the first to evaluate the shape of this association
We found that lower serum retinol levels were associated with decreased overall and CRC-specific survival even after comprehensive adjustment for serum 25(OH)D3 and other covariates
Summary
Colorectal cancer (CRC) is the fourth most common cause of cancer mortality worldwide [1].in patients with established disease, the ascertainment of factors that may ameliorate their prognosis is highly needed.Nutrients 2018, 10, 510; doi:10.3390/nu10040510 www.mdpi.com/journal/nutrientsVitamin A (retinol) is a nutrient obtained from the diet as either preformed vitamin A (retinol, retinyl esters) derived from animal products or provitamin A carotenoids (α-carotene, β-carotene, and β-cryptoxanthin) in colored vegetables [2]. Colorectal cancer (CRC) is the fourth most common cause of cancer mortality worldwide [1]. In patients with established disease, the ascertainment of factors that may ameliorate their prognosis is highly needed. Vitamin A (retinol) is a nutrient obtained from the diet as either preformed vitamin A (retinol, retinyl esters) derived from animal products or provitamin A carotenoids (α-carotene, β-carotene, and β-cryptoxanthin) in colored vegetables [2]. Retinol is enzymatically oxidized to all-trans retinal and to retinoic acid (RA) that exists in the form of two isomers called all-trans. RA and 9-cis RA which are further transported to the nucleus to exert their physiological actions [3]. Retinol is supposed to have a role in inhibiting CRC progression. Suggested mechanisms include decreasing signaling via the major pathways that promote cell invasion and proliferation such as the β-catenin pathway [4], increasing tumor cell differentiation, and promoting tumor cell apoptosis [4,5,6,7,8]
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