Calcium Intake and Ion Transporter Genetic Polymorphisms Interact in Human Colorectal Neoplasia Risk in a 2-Phase Study. Issue 11 (27th August 2014)

• Record Type: Journal Article
• Authors: Zhu, Xiangzhu; Liang, Ji; Shrubsole, Martha J.; Ness, Reid M.; Cai, Qiuyin; Long, Jirong; Chen, Zhi; Li, Guoliang; Wiese, Dawn; Zhang, Bing; Smalley, Walter E.; Edwards, Todd L.; Giovannucci, Edward; Zheng, Wei; Dai, Qi
• Is Part Of: Journal of nutrition. Volume 144:Issue 11(2014)
• Page Start: 1734
• Page End: 1741
• Publication Date: 2014-08-27
• Subjects: Nutrition -- Periodicals; Diet -- Periodicals; 613.205
• DOI: 10.3945/jn.114.196709
• Languages: English
• ISSNs: 0022-3166

Abstract

Abstract: Background: 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. Objective: We hypothesized that polymorphisms in KCNJ1, SLC12A1, and 7 other genes may modify the association between calcium intake and colorectal neoplasia risk. Methods: We conducted a 2-phase study in 1336 cases and 2891 controls from the Tennessee Colorectal Polyp Study. Results: 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. Conclusion: These findings, if confirmed, will be critical for the development of personalized prevention strategies for colorectal cancer.