Abstract CT534: Magnesium treatment on the demethylation of chemokine (C-X-C motif) ligand 9 (CXCL9) gene, results from the personalized prevention of colorectal cancer trial

Abstract

Abstract Background: Chemokine ligand 9 (CXCL9), a T-cell chemoattractant, plays a critical role in regulating antitumor immunity in cancer immunotherapy, i.e., clinical responses to anti-PD(L)-1 treatment. Very recently, CXCL9 was identified as the strongest contributor to the “inflammatory clock of aging”, linked to age-related chronic inflammation. Due to the critical role of magnesium (Mg) in regulating inflammatory responses, this study aims to investigate the effect of Mg treatment on DNA methylation changes in CXCL9. Methods: The Personalized Prevention of Colorectal Cancer Trial conducted at Vanderbilt University Medical Center was a double-blind 2 × 2 factorial randomized controlled trial of 240 participants who completed the study. Participants aged from 40 to 85 years, had a daily calcium intake 700-2000 mg and calcium:magnesium intake ratio ≥2.6 based on the average of the two baseline 24-hour dietary recalls. Results: Among three CpG sites, a 12-week personalized dose of Mg supplementation marginally increased the 5-hydroxymethylcytosine methylation, a measure of active demethylation, at CpG site 04038163 (3'UTR of CXCL9 gene) by 7.0% compared to the placebo group (p=0.07). Although the overall effect was not significant or of borderline significance, Mg treatment significantly reduced the levels of 5-hydroxymethylcytosine by 3.7% at the CpG site 12793812 (body of CXCL9 gene) among those with aged 60 years or above (p=0.03). Conclusions: These findings indicate that Mg treatment modified the demethylation process in the CXCL9 gene, a critical regulator of immune responses and inflammation. Future studies are needed to examine if Mg treatment also changes the circulating levels of CXCL9. Citation Format: Xiangzhu Zhu, Xiang Huang, Yinan Zheng, Wei Zhang, Lihua Shu, Reid Ness, Harvey J Murff, Chang Yu, Martha J Shrubsole, Lifang Hou, Qi Dai. Magnesium treatment on the demethylation of chemokine (C-X-C motif) ligand 9 (CXCL9) gene, results from the personalized prevention of colorectal cancer trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT534.