TY - JOUR
T1 - Genetic variation in SLC7A2 interacts with calcium and magnesium intakes in modulating the risk of colorectal polyps
AU - Sun, Pin
AU - Zhu, Xiangzhu
AU - Shrubsole, Martha J.
AU - Ness, Reid M.
AU - Hibler, Elizabeth A.
AU - Cai, Qiuyin
AU - Long, Jirong
AU - Chen, Zhi
AU - Li, Guoliang
AU - Hou, Lifang
AU - Smalley, Walter E.
AU - Edwards, Todd L.
AU - Giovannucci, Edward
AU - Zheng, Wei
AU - Dai, Qi
N1 - Funding Information:
Funding: This study was supported through the National Center for Complementary and Alternative Medicine grant R01AT004660 and Office of Dietary Supplements, National Cancer Institute grants R01 CA149633 (to Q.D.) and U01 CA182364 (to Q.D. and T.L.E.) as well as parent studies P50CA95103 (to W.Z.) and R01CA121060 (to W.Z.) and the American Institute for Cancer Research grant #08A074 (to Q.D.). The survey and sample processing for the Tennessee Colorectal Polyps Study were conducted by the Survey and Biospecimen Shared Resource supported in part by the Vanderbilt-Ingram Cancer Center (P30 CA68485). Additional support was provided by the Vanderbilt Clinical and Translational Research Scholar award (5KL2RR024975) to T.L.E.
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - Solute carrier family 7, member 2 (SLC7A2) gene encodes a protein called cationic amino acid transporter 2, which mediates the transport of arginine, lysine and ornithine. L-Arginine is necessary for cancer development and progression, including an important role in colorectal cancer pathogenesis. Furthermore, previous studies found that both calcium and magnesium inhibit the transport of arginine. Thus, calcium, magnesium or calcium:magnesium intake ratio may interact with polymorphisms in the SLC7A2 gene in association with colorectal cancer. We conducted a two-phase case–control study within the Tennessee Colorectal Polyps Study. In the first phase, 23 tagging single-nucleotide polymorphisms in the SLC7A2 gene were included for 725 colorectal adenoma cases and 755 controls. In the second phase conducted in an independent set of 607 cases and 2113 controls, we replicated the significant findings in the first phase. We observed that rs2720574 significantly interacted with calcium:magnesium intake ratio in association with odds of adenoma, particularly multiple/advanced adenoma. In the combined analysis, among those with a calcium:magnesium intake ratio below 2.78, individuals who carried GC/CC genotypes demonstrated higher odds of adenoma [OR (95% CI):1.36 (1.11–1.68)] and multiple/advanced adenoma [OR (95% CI): 1.68 (1.28, 2.20)] than those who carried the GG genotype. The P values for interactions between calcium:magnesium intake ratio and rs2720574 were.002 for all adenomas and <.001 for multiple/advanced adenoma. Among those with the GG genotype, a high calcium:magnesium ratio was associated with increased odds of colorectal adenoma [OR (95% CI): 1.73 (1.27–2.36)] and advanced/multiple adenomas [1.62 (1.05–2.50)], whereas among those with the GC/CC genotypes, high calcium:magnesium ratio was related to reduced odds of colorectal adenoma [0.64 (0.42–0.99)] and advanced/multiple adenomas [0.55 (0.31–1.00)].
AB - Solute carrier family 7, member 2 (SLC7A2) gene encodes a protein called cationic amino acid transporter 2, which mediates the transport of arginine, lysine and ornithine. L-Arginine is necessary for cancer development and progression, including an important role in colorectal cancer pathogenesis. Furthermore, previous studies found that both calcium and magnesium inhibit the transport of arginine. Thus, calcium, magnesium or calcium:magnesium intake ratio may interact with polymorphisms in the SLC7A2 gene in association with colorectal cancer. We conducted a two-phase case–control study within the Tennessee Colorectal Polyps Study. In the first phase, 23 tagging single-nucleotide polymorphisms in the SLC7A2 gene were included for 725 colorectal adenoma cases and 755 controls. In the second phase conducted in an independent set of 607 cases and 2113 controls, we replicated the significant findings in the first phase. We observed that rs2720574 significantly interacted with calcium:magnesium intake ratio in association with odds of adenoma, particularly multiple/advanced adenoma. In the combined analysis, among those with a calcium:magnesium intake ratio below 2.78, individuals who carried GC/CC genotypes demonstrated higher odds of adenoma [OR (95% CI):1.36 (1.11–1.68)] and multiple/advanced adenoma [OR (95% CI): 1.68 (1.28, 2.20)] than those who carried the GG genotype. The P values for interactions between calcium:magnesium intake ratio and rs2720574 were.002 for all adenomas and <.001 for multiple/advanced adenoma. Among those with the GG genotype, a high calcium:magnesium ratio was associated with increased odds of colorectal adenoma [OR (95% CI): 1.73 (1.27–2.36)] and advanced/multiple adenomas [1.62 (1.05–2.50)], whereas among those with the GC/CC genotypes, high calcium:magnesium ratio was related to reduced odds of colorectal adenoma [0.64 (0.42–0.99)] and advanced/multiple adenomas [0.55 (0.31–1.00)].
KW - Calcium
KW - Colorectal polyps
KW - Gene–nutrient interaction
KW - Magnesium
KW - SLC7A2
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U2 - 10.1016/j.jnutbio.2017.04.016
DO - 10.1016/j.jnutbio.2017.04.016
M3 - Article
C2 - 28501704
AN - SCOPUS:85019060075
SN - 0955-2863
VL - 47
SP - 35
EP - 40
JO - Journal of Nutritional Biochemistry
JF - Journal of Nutritional Biochemistry
ER -
