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

Abstract

The SLC8A1 (solute carrier family 8, member 1) gene, encoding Na+/Ca2+ exchanger, is essential in regulating calcium reabsorption and homeostasis. Calcium homeostasis plays a key role in cell proliferation and apoptosis. We hypothesized that polymorphisms in five calcium-regulating genes (SLC8A1, ATP2B1, CALB1, CALB2, and CABP1) interact with calcium intake in relation to the risk of colorectal neoplasia. A two-phase (discovery and replication) study was conducted within the Tennessee Colorectal Polyp Study, including a total of 1275 cases and 2811 controls. In Phase I, we identified six out of 135 SNPs that significantly interacted with calcium intake in relation to adenoma risk. In Phase II, the calcium intake by rs4952490 (SLC8A1) interaction was replicated (P interaction=0.048). 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, KCNJ1 and SLC12A1 SNPs, carriers of variant alleles in at least two genes and with calcium intake above the DRI (1000 mg/day) were approximately 30–57% 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 when calcium intake was below 2500 mg per day. These findings, if confirmed, may provide a new avenue for the personalized prevention of colorectal adenoma and cancer.

MicroRNAs associated with lung squamous cell carcinoma: New prognostic biomarkers and therapeutic targets

“…miR‐515, miR‐577, and miR‐383 all silenced these six pivotal genes separately when they were highly expressed. DLGAP5 is associated with the development of a variety of tumors, such as ovarian cancer, breast cancer, and NSCLC, due to its ability to inhibit mitosis and block cell cycle progression . Calcium is one of the key factors in stabilizing the cell cycle, and CALB1 can interfere with the resorption and homeostatic processes of calcium, ultimately regulating cell apoptosis .…”

“…DLGAP5 is associated with the development of a variety of tumors, such as ovarian cancer, breast cancer, and NSCLC, due to its ability to inhibit mitosis and block cell cycle progression. 57,58 Calcium is one of the key factors in stabilizing the cell cycle, and CALB1 can interfere with the resorption and homeostatic processes of calcium, ultimately regulating cell apoptosis. 59 In addition, studies have shown that CALB1 can play a role in early tumor diagnosis and recurrence prediction.…”

Identification of key candidate genes and pathways in glioblastoma by integrated bioinformatical analysis

“…However, CABP1 has rarely been studied in the field of oncology. Certain studies have demonstrated that aberrant CABP1 expression was associated with adenoma risk, particularly for multiple/advanced adenomas (44,48,49). In addition, Zhang et al (50) previously reported that CABP1 is upregulated in glioblastoma tissues compared with normal brain tissues.…”

The SLC transporter in nutrient and metabolic sensing, regulation, and drug development

“…GWAS analysis demonstrated that variants of SLC8A1 were closely related to the risk of colorectal neoplasia and calcium intake and inversely correlated with colorectal adenomas (Zhao et al, 2017a). SLC8A1 functions as a Na + /Ca 2+ exchanger and mediates the extrusion of Ca 2+ ion across the cell membrane (Khananshvili, 2013).…”