Association between magnesium intake and risk of colorectal cancer among postmenopausal women.

PURPOSE: Data relating to magnesium intake and colorectal cancer (CRC) risk in postmenopausal women are incomplete. We investigated the association between total magnesium intake and the risk of CRC in an ethnically diverse cohort of postmenopausal women enrolled in the Women's Health Initiative. METHODS: Self-reported dietary and supplemental magnesium were combined to form total magnesium intake. Invasive incident CRC was the primary outcome. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). RESULTS: During an average follow-up of 13 years (1,832,319 person-years), of the 140,601 women included for analysis, 2,381 women were diagnosed with CRC (1,982 colon cancer and 438 rectal cancer). After adjustment for potential confounding variables, an inverse association was observed in the highest quintile of total magnesium intake compared to the lowest quintile for risk of CRC (HR 0.79, 95% CI 0.67, 0.94, p trend < 0.0001) and colon cancer (HR 0.80, 95% CI 0.66, 0.97, p trend < 0.0001). A borderline significant inverse association was detected in the highest versus the lowest quintile of total magnesium intake for rectal cancer (HR 0.76, 95% CI 0.51, 1.13, p trend < 0.001). CONCLUSIONS: Findings from this study support the hypothesis that magnesium intake around 400 mg/day from both dietary and supplemental sources is associated with a lower incidence of CRC in postmenopausal women.

Methylation of arsenic by recombinant human wild-type arsenic (+3 oxidation state) methyltransferase and its methionine 287 threonine (M287T) polymorph: Role of glutathione.

Arsenic (+3 oxidation state) methyltransferase (AS3MT) is the key enzyme in the pathway for methylation of arsenicals. A common polymorphism in the AS3MT gene that replaces a threonyl residue in position 287 with a methionyl residue (AS3MT/M287T) occurs at a frequency of about 10% among populations worldwide. Here, we compared catalytic properties of recombinant human wild-type (wt) AS3MT and AS3MT/M287T in reaction mixtures containing S-adenosylmethionine, arsenite (iAs(III)) or methylarsonous acid (MAs(III)) as substrates and endogenous or synthetic reductants, including glutathione (GSH), a thioredoxin reductase (TR)/thioredoxin (Trx)/NADPH reducing system, or tris (2-carboxyethyl) phosphine hydrochloride (TCEP). With either TR/Trx/NADPH or TCEP, wtAS3MT or AS3MT/M287T catalyzed conversion of iAs(III) to MAs(III), methylarsonic acid (MAs(V)), dimethylarsinous acid (DMAs(III)), and dimethylarsinic acid (DMAs(V)); MAs(III) was converted to DMAs(III) and DMAs(V). Although neither enzyme required GSH to support methylation of iAs(III) or MAs(III), addition of 1mM GSH decreased K(m) and increased V(max) estimates for either substrate in reaction mixtures containing TR/Trx/NADPH. Without GSH, V(max) and K(m) values were significantly lower for AS3MT/M287T than for wtAS3MT. In the presence of 1mM GSH, significantly more DMAs(III) was produced from iAs(III) in reactions catalyzed by the M287T variant than in wtAS3MT-catalyzed reactions. Thus, 1mM GSH modulates AS3MT activity, increasing both methylation rates and yield of DMAs(III). AS3MT genotype exemplified by differences in regulation of wtAS3MT and AS3MT/M287T-catalyzed reactions by GSH may contribute to differences in the phenotype for arsenic methylation and, ultimately, to differences in the disease susceptibility in individuals chronically exposed to inorganic arsenic.