Calcium intake and ion transporter genetic polymorphisms interact in human colorectal neoplasia risk in a 2-phase study.

Zhu X, Liang J, Shrubsole MJ, Ness RM, Cai Q, Long J, Chen Z, Li G, Wiese D, Zhang B, Smalley WE, Edwards TL, Giovannucci E, Zheng W, Dai Q
J Nutr. 2014 144 (11): 1734-41

PMID: 25165391 · PMCID: PMC4195417 · DOI:10.3945/jn.114.196709

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.

© 2014 American Society for Nutrition.

MeSH Terms (15)

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

Connections (6)

This publication is referenced by other Labnodes entities:

Links