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

Study Overview
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Brief Summary
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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.

Official Title
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Methylomic Biomarkers for Magnesium Deficiency and Colon Neoplasia Prevention

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Dietary Supplement: Magnesium glycinate
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: GG genotype and magnesium treatment<br>Participants who have the GG genotype will be assigned to magnesium glycinate | Dietary Supplement: Magnesium glycinate<br>* Oral administration of magnesium glycinate daily for 12 weeks<br>|
| Placebo Comparator: GG genotype and placebo<br>Participants who have the GG genotype will be assigned to placebo group | Dietary Supplement: Placebo<br>* Oral administration of identical-appearing placebo daily for 12 weeks<br>|
| Active Comparator: GA/AA genotype and magnesium treatment<br>Participants who have the GA/AA genotype will be assigned to magnesium glycinate | Dietary Supplement: Magnesium glycinate<br>* Oral administration of magnesium glycinate daily for 12 weeks<br>|
| Placebo Comparator: GA/AA genotype and Placebo<br>Participants who have the GA/AA genotype will be assigned to placebo group | Dietary Supplement: Placebo<br>* Oral administration of identical-appearing placebo daily for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 5-mC and 5-hmC assays | DNA was extract from WBC samples and measured by using TAB-Seq & TAB-Array protocol | 12 Weeks | 
| Serum magnesium |  | 12 Weeks | 
| Plasma methionine cycle metabolites | Plasma SAM, SAH, homocysteine and methionine measured by stable-isotope dilution liquid chromatography-electrospray tandem mass spectrometry (LC-ESI-MS/MS) | 12 Weeks |