Abstract
To investigate the association between serum calcium and risk of breast cancer using a large cohort and a systematic review with meta-analysis. From the Swedish Apolipoprotein Mortality Risk (AMORIS) Study we included 229,674 women who had baseline measurements of serum total calcium and albumin. Multivariable Cox regression was used to assess the association between total and albumin-corrected calcium and breast cancer risk. For the systematic review, an electronic search of MEDLINE and EMBASE databases was performed to identify other prospective cohorts assessing the relationship between serum calcium and breast cancer risk. We pooled the results of our AMORIS cohort with other eligible studies in a meta-analysis using a random effects model. I2 test was used to assess heterogeneity. In the AMORIS study, 10,863 women were diagnosed with breast cancer (mean follow-up: 19 years). We found an inverse association between total serum calcium and breast cancer when comparing the fourth quartile to the first quartile (HR: 0.94, 95% CI: 0.88–0.99, p value for trend 0.04) and similar results using albumin-corrected calcium. In the systematic review, we identified another two prospective cohorts evaluating pre-diagnostic serum total calcium and breast cancer. Combining these studies and our findings in AMORIS in a meta-analysis showed a protective effect of serum calcium against breast cancer, with a summary RR of 0.80 (95% CI: 0.66–0.97). No substantial heterogeneity was observed. Our findings in AMORIS and the meta-analysis support an inverse association between serum calcium and breast cancer risk, which warrants mechanistic investigations.
Highlights
There is ongoing debate surrounding the role of calcium in cancer prevention
In order to elucidate the role of circulating calcium levels in breast cancer development, we investigated the association between prediagnostic serum calcium and breast cancer risk in a large prospective cohort study including more than 220,000 women
When assessing total serum calcium in relation to breast cancer risk, we found that higher calcium corresponded to a lower risk of breast cancer, with a hazard ratio (HR) for breast cancer of 0.78% and 95% confidence intervals (CI) of 0.63 to 0.97
Summary
There is ongoing debate surrounding the role of calcium in cancer prevention. In the context of breast cancer, current findings are mostly focused on dietary calcium with limited evidence on biomarker levels, denoting an unclear role of the calcium metabolism. An inverse association with dietary calcium intake was shown in a meta-analysis including fifteen observational studies [1], with an approximate 19% reduction in breast cancer risk observed among those in highest quantile of calcium intake compared to the lowest quantile. This protective effect is thought to be majorly underlain by chemopreventative actions of 1,25-dihydroxyvitamin D (1,25(OH)2D), the active form of vitamin D, a well-known regulator of calcium. Evidence on the role of circulating calcium levels in breast cancer is limited [6,7]
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