Abstract A62: Magnesium, calcium, and colorectal adenoma recurrence: Results from a randomized trial

Mean magnesium intake in the US population is similar to that in East Asian populations with traditionally low risks of colorectal cancer and other chronic diseases, while the ratio of calcium to magnesium is much higher in the US population. It was recently reported that intakes of calcium or magnesium were associated with a reduced risk of adenoma or hyperplastic polyps only when dietary ratios of calcium to magnesium intake was low.

To test whether calcium supplementation reduces the risk of colorectal adenoma recurrence only when calcium/magnesium intake ratio is low. Design: The Calcium Polyp Prevention Study was a double-blind, placebo-controlled, randomized trial of 4 years of calcium supplementation (1000 mg) for the prevention of colorectal adenoma recurrence among 930 subjects. Participants underwent two follow-up colonoscopies, 1 year and 4 years after the qualifying exam. A validated semi-quantitative food frequency questionnaire was given at study entry and year 4 to obtain subjects’ usual diet over the previous year. The primary outcome in this analysis was the recurrence of adenomasduring the main risk period (i.e. adenomas detected after the year 1 colonoscopy through the year 4 exam). This end point allowed for a latent period of calcium effect and minimized the number of adenomas overlooked at the qualifying colonoscopy.

We found that dietary ratios of calcium to magnesium intake modified the effect of calcium treatment on adenoma recurrence (p for interaction: 0.075 for all adenoma and 0.046 for tubular adenoma during the main risk period). Calcium supplementation reduced the risk of adenoma recurrence only if the dietary ratio of calcium to magnesium intake was low before treatment and remained low during the treatment period. The RR (95%CI) was 0.68 (0.52-0.90) among those with the baseline ratio below the median in comparison to 0.98 (95%CI=0.75-1.28) for those above. Findings were similar when the intake ratio at year 4 was considered and when we repeated the analyses using adenomas detected during the full study period (e.g. including adenomas identified at year 1) and found very similar results. The sample size, however, became small when advanced adenomas were used as outcome; none of the associations were significant in the stratified analyses by calcium: magnesium ratio and the calcium effect did not differ substantially by ratio stratum (p for interaction, 0.575). We also found that high dietary intake of magnesium was related to a reduced risk of adenoma recurrence among subjects in the calcium treatment arm with a low ratio of calcium to magnesium intake; the RRs (95%CIs) for any adenoma were 0.66 (0.39-1.13) and 0.58 (0.32-1.06) for the intermediate and the highest intake tertiles vs. the lowest intake tertile of magnesium (p for trend, 0.054). There was no association observed in the placebo arm. Conclusions: We found that calcium supplementation reduced the risk of adenomas only among subjects with a low calcium:magnesium intake ratio. These findings, if confirmed, may provide a new avenue for the personalized prevention of colorectal cancer. The abstract is on behalf of the Polyp Prevention Study Group.

Citation Information: Cancer Prev Res 2008;1(7 Suppl):A62.