Abstract
BackgroundObservational studies have indicated that high calcium intake may prevent colorectal cancer, but as for randomized trials the results are inconclusive. Meanwhile, limited data on the link between serum calcium and cancer risk is available. We investigated the relation between serum calcium and risk of different gastrointestinal cancers in a prospective study.MethodsA cohort based on 492,044 subjects with baseline information on calcium (mmol/L) and albumin (g/L) was selected from the Swedish Apolipoprotein MOrtality RISk (AMORIS) study. Multivariable Cox proportional hazard models were used to analyse associations between standardised levels, quartiles and age/sex-specific categories of serum calcium and risk of oesophageal, stomach, colon, rectal cancer and also colorectal cancer combined, while taking into account serum albumin and other comorbidities.ResultsDuring 12 years of follow-up, we identified 323 incident oesophageal cancers, 782 stomach cancers, 2519 colon cancers, and 1495 rectal cancers. A positive association was found between albumin-adjusted serum calcium and risk of oesophageal [HR: 4.82 (95% CI: 2.07 – 11.19) for high compared to normal age-specific calcium levels] and colon cancer [e.g. HR: 1.07 (95% CI: 1.00 – 1.14) for every SD increase of calcium] as well as colorectal cancer [e.g. HR: 1.06 (95% CI: 1.02-1.11) for every SD increase of calcium] in women. In men there were similar but weaker non-statistically significant trends.ConclusionThe positive relation between serum calcium, oesophageal cancer and colorectal cancer calls for further studies including calcium regulators to evaluate whether there is a true link between calcium metabolism and development of gastrointestinal cancer.
Highlights
Observational studies have indicated that high calcium intake may prevent colorectal cancer, but as for randomized trials the results are inconclusive
When using albumin-corrected calcium, we found a higher risk of colon cancer in those in higher albumincorrected calcium quartiles., Additional adjustments for gender, socio-economic status (SES), and Charlson co-morbidity index (CCI) resulted in a stronger association with colon cancer risk [HR for colon cancer: 1.13, 1.10 (0.98 – 1.28), and 1.16 (1.06 – 1.34) for the 2nd, 3rd, and 4th quartiles of calcium, respectively; P-value for trend 0.007] and a statistically significant association with colorectal cancer risk [e.g. HR for colorectal cancer: 1.09, 1.09 (0.99 – 1.20), and 1.13 (1.03 – 1.34) for the 2nd, 3rd, and 4th quartiles of calcium, respectively; P-value for trend 0.02]
The present study showed a lower risk of colon cancer in those in higher serum calcium quartiles but higher risk for rectal cancer in those with high age-specific calcium levels
Summary
Observational studies have indicated that high calcium intake may prevent colorectal cancer, but as for randomized trials the results are inconclusive. Limited data on the link between serum calcium and cancer risk is available. We investigated the relation between serum calcium and risk of different gastrointestinal cancers in a prospective study. A role of dietary calcium in colorectal cancer prevention has been suggested [1], but there is lack of epidemiological evidence linking serum calcium and gastrointestinal cancer risk. High calcium intake has been shown to suppress cell cycle, promote apoptosis and reduce formation of colonic tumour in animal studies [2]. A pooled analysis including 534,536 individuals from ten cohort studies revealed a lower colorectal cancer the risk of gastrointestinal cancer while taking into account serum albumin and other co-morbidities warrants further investigation
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