Methylomic Biomarkers for Magnesium Deficiency in the Personalized Prevention of Colorectal Cancer Trial

Methylomic Biomarkers for Magnesium Deficiency in the Personalized Prevention of Colorectal Cancer Trial

Based on the magnesium (Mg) tolerance test, the "gold standard" test of Mg status, more than 50% US participants had Mg deficiency. Observations suggest that the associations between high Mg intake and disease risks may completely differ by the underlying Mg status. Due to major limitations, the Mg tolerance test is not used in conventional clinical practice and rarely used in research. Instead, serum Mg is used for clinical diagnosis. However, serum Mg performs very poorly at identifying those with Mg deficiency. There is a great need to develop implementable, sensitive, and specific biomarkers which can be easily used for identifying people with Mg deficiency. It is known that DNA methylation changes are inducible by environmental exposures, including nutrients, and reversible when the exposure disappears. We propose to identify 5-hmC/5-mC biomarkers for Mg deficiency by a 4- phase EWAS study in the "Personalized Prevention of Colorectal Cancer Trial [PPCCT, R01CA149633; PI, Dai & Yu]" with a total of 240 participants. Mg tolerance test will be used as the gold standard. Finally, using newly identified biomarkers, we will evaluate if 12-week Mg treatment reduces TRPM7 expression, essential in Mg homeostasis and colorectal carcinogenesis, in rectal tissues only among those with Mg deficiency.

Plasma SAM, SAH, homocysteine and methionine measured by stable-isotope dilution liquid chromatography-electrospray tandem mass spectrometry (LC-ESI-MS/MS)

Inclusion Criteria: Participants from our parent study (Personalized Prevention of Colorectal Cancer Trial, NCT#01105169, IRB#100106); Participants consent to store/share biospecimens for future research. Exclusion Criteria: 1. Participants cannot provide their blood samples in the parent study.