Interactions between calcium intake and polymorphisms in genes essential for calcium reabsorption and risk of colorectal neoplasia in a two‐phase study

Abstract

BackgroundCalcium homeostasis plays a key role in cell proliferation and apoptosis. We hypothesized that polymorphisms in the SLC8A1 and other four calcium‐regulating genes interact with calcium intake in relation to the risk of colorectal neoplasia.DesignA two‐phase (discovery and replication) study was conducted within the Tennessee Colorectal Polyp Study, including a total of 1275 cases and 2811 controls.ResultsIn this two phase study, the interaction between rs4952490 (SLC8A1) and calcium intake in relation to adenoma risk was identified and replicated. We found an inverse association between calcium intake (1000‐2000 mg/day) and colorectal adenomas, particularly for multiple/advanced adenomas, among the G‐allele carriers but not among homozygous carriers of the common variant (A) in rs4952490. In the joint analysis of SLC8A1, KCNJ1and SLC12A1SNPs, carriers of variant alleles in at least two genes and with calcium intake above the DRI (1000 mg/day) were approximately 40‐60% less likely to have adenomas than those whose calcium intake was below the DRI. The association was stronger for multiple/advanced adenomas. No association was found among those who did not carry any variant alleles in these genes.ConclusionsThese findings, if confirmed, may provide a new avenue for the personalized prevention of colorectal adenoma and cancer.