Genetic variation in SLC7A2 interacts with calcium and magnesium intakes in modulating the risk of colorectal polyps

Pin Sun, Xiangzhu Zhu, Martha J. Shrubsole, Reid M. Ness, Elizabeth A. Hibler, Qiuyin Cai, Jirong Long, Zhi Chen, Guoliang Li, Lifang Hou, Walter E. Smalley, Todd L. Edwards, Edward Giovannucci, Wei Zheng, Qi Dai*

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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)].

Original languageEnglish (US)
Pages (from-to)35-40
Number of pages6
JournalJournal of Nutritional Biochemistry
Volume47
DOIs
StatePublished - Sep 1 2017

Fingerprint

Polyps
Adenoma
Magnesium
Calcium
Arginine
Genes
Genotype
Polymorphism
Cationic Amino Acid Transporter 2
Colorectal Neoplasms
Ornithine
Lysine
Nucleotides
Single Nucleotide Polymorphism

Keywords

  • Calcium
  • Colorectal polyps
  • Gene–nutrient interaction
  • Magnesium
  • SLC7A2

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

Cite this

Sun, Pin ; Zhu, Xiangzhu ; Shrubsole, Martha J. ; Ness, Reid M. ; Hibler, Elizabeth A. ; Cai, Qiuyin ; Long, Jirong ; Chen, Zhi ; Li, Guoliang ; Hou, Lifang ; Smalley, Walter E. ; Edwards, Todd L. ; Giovannucci, Edward ; Zheng, Wei ; Dai, Qi. / Genetic variation in SLC7A2 interacts with calcium and magnesium intakes in modulating the risk of colorectal polyps. In: Journal of Nutritional Biochemistry. 2017 ; Vol. 47. pp. 35-40.
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abstract = "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)].",
keywords = "Calcium, Colorectal polyps, Gene–nutrient interaction, Magnesium, SLC7A2",
author = "Pin Sun and Xiangzhu Zhu and Shrubsole, {Martha J.} and Ness, {Reid M.} and Hibler, {Elizabeth A.} and Qiuyin Cai and Jirong Long and Zhi Chen and Guoliang Li and Lifang Hou and Smalley, {Walter E.} and Edwards, {Todd L.} and Edward Giovannucci and Wei Zheng and Qi Dai",
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Sun, P, Zhu, X, Shrubsole, MJ, Ness, RM, Hibler, EA, Cai, Q, Long, J, Chen, Z, Li, G, Hou, L, Smalley, WE, Edwards, TL, Giovannucci, E, Zheng, W & Dai, Q 2017, 'Genetic variation in SLC7A2 interacts with calcium and magnesium intakes in modulating the risk of colorectal polyps', Journal of Nutritional Biochemistry, vol. 47, pp. 35-40. https://doi.org/10.1016/j.jnutbio.2017.04.016

Genetic variation in SLC7A2 interacts with calcium and magnesium intakes in modulating the risk of colorectal polyps. / Sun, Pin; Zhu, Xiangzhu; Shrubsole, Martha J.; Ness, Reid M.; Hibler, Elizabeth A.; Cai, Qiuyin; Long, Jirong; Chen, Zhi; Li, Guoliang; Hou, Lifang; Smalley, Walter E.; Edwards, Todd L.; Giovannucci, Edward; Zheng, Wei; Dai, Qi.

In: Journal of Nutritional Biochemistry, Vol. 47, 01.09.2017, p. 35-40.

Research output: Contribution to journalArticle

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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

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)].

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