One‐carbon metabolite ratios as functional B‐vitamin markers and in relation to colorectal cancer risk. Issue 5 (7th December 2018) - Gylling, Björn
Abstract : One‐carbon metabolism biomarkers are easily measured in plasma, but analyzing them one at a time in relation to disease does not take into account the interdependence of the many factors involved. The relative dynamics of major one‐carbon metabolism branches can be assessed by relating the functional B‐vitamin marker total homocysteine (tHcy) to transsulfuration (total cysteine) and methylation (creatinine) outputs. We validated the ratios of tHcy to total cysteine (Hcy:Cys), tHcy to creatinine (Hcy:Cre) and tHcy to cysteine to creatinine (Hcy:Cys:Cre) as functional markers of B‐vitamin status. We also calculated the associations of these ratios to colorectal cancer (CRC) risk. Furthermore, the relative contribution of potential confounders to the variance of the ratio‐based B‐vitamin markers was calculated by linear regression in a nested case–control study of 613 CRC cases and 1, 190 matched controls. Total B‐vitamin status was represented by a summary score comprising Z ‐standardized plasma concentrations of folate, cobalamin, betaine, pyridoxal 5′‐phosphate and riboflavin. Associations with CRC risk were estimated using conditional logistic regression. We found that the ratio‐based B‐vitamin markers all outperformed tHcy as markers of total B‐vitamin status, in both CRC cases and controls. In addition, associations with CRC risk were similar for the ratio‐based B‐vitamin markers and total B‐vitamin status (approximately 25% lower risk for high vs . low B‐vitamin status). In conclusion, ratio‐based B‐vitamin markers were good predictors of total B‐vitamin status and displayed similar associations as total B‐vitamin status with CRC risk. Since tHcy and creatinine are routinely clinically analyzed, Hcy:Cre could be easily implemented in clinical practice. Abstract : What's new? While total homocysteine (tHcy) levels are an important biomarker of B‐vitamin status and may be predictive for colorectal cancer (CRC) risk, they are influenced by a variety of factors, such as age, sex, and lifestyle. Here, tHcy was compared to ratio‐based biomarkers of total B‐vitamin status to assess functionality and relation to CRC risk. In CRC patients and controls, the ratio‐based markers outperformed tHcy as indicators of total B‐vitamin status. Their association with CRC risk was similar to that of total B‐vitamin status. Ratio‐based biomarkers could fill a valuable role in assessments of functional B‐vitamin levels and disease risk.