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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, OBJECTIVE, METHODS, RESULTS. Meshes: Adenoma, Adult, Aged, Calcium, Case-Control Studies, Colorectal Neoplasms, Gene Expression Regulation, Neoplastic, Genotype, Humans, Middle Aged, Odds Ratio, Polymorphism, Genetic, Potassium Channels, Inwardly Rectifying, Risk Factors, Solute Carrier Family 12, Member 1.
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Do calcium intake and ion transporter genetic polymorphisms interact in human colorectal neoplasia risk in a 2-phase study? Context: The kidney-specific sodium-potassium-chloride cotransporter (NKCC2) protein encoded by solute carrier family 12 member 1 (SLC12A1) is the direct downstream effector of the inward-rectifier potassium channel (ROMK) encoded by potassium inwardly-rectifying channel, subfamily J, member 1 (KCNJ1), both of which are critical for calcium reabsorption in the kidney. We hypothesized that polymorphisms in KCNJ1, SLC12A1, and 7 other genes may modify the association between calcium intake and colorectal neoplasia risk. We conducted a 2-phase study in 1336 cases and 2891 controls from the Tennessee Colorectal Polyp Study. In phase I, we identified 5 single-nucleotide polymorphisms (SNPs) that significantly interacted with calcium intake in adenoma risk. In phase II, rs2855798 in KCNJ1 was replicated. In combined analysis of phases I and II, the P values for interactions between calcium intake and rs2855798 were 1 × 10(-4) for all adenoma and 5 × 10(-3) for multiple/advanced adenoma. The highest calcium intake was not associated with risk among those with no variant allele but was significantly associated with a 41% reduced adenoma risk among those who carried at least 1 variant allele in KCNJ1. The corresponding reduction in risk of multiple or advanced adenomas was 52% among those with at least 1 variant allele. The P values for interactions between calcium intake and combined SNPs from the KCNJ1 and SLC12A1 genes were 7.5 × 10(-5) for adenoma and 9.9 × 10(-5) for multiple/advanced adenoma. The highest calcium intake was not associated with risk among those with nonvariant alleles in 2 genes but was significantly associated with a 34% reduced adenoma risk among those who carried a variant allele in 1 of the genes. The corresponding reduction in risk of multiple or advanced adenomas was 64% among those with variant alleles in both genes.
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These findings, if confirmed, will be critical for the development of personalized prevention strategies for colorectal cancer. Final Decision: yes