Calcium/magnesium intake ratio, but not magnesium intake, interacts with genetic polymorphism in relation to colorectal neoplasia in a two-phase study

Xiangzhu Zhu; Martha J. Shrubsole; Reid M. Ness; Elizabeth A. Hibler; Qiuyin Cai; Jirong Long; Zhi Chen; Guoliang Li; Ming Jiang; Lifang Hou; Edmond K. Kabagambe; Bing Zhang; Walter E. Smalley; Todd L. Edwards; Edward L. Giovannucci; Wei Zheng; Qi Dai

doi:10.1002/mc.22387

Calcium/magnesium intake ratio, but not magnesium intake, interacts with genetic polymorphism in relation to colorectal neoplasia in a two-phase study

Xiangzhu Zhu, Martha J. Shrubsole, Reid M. Ness, Elizabeth A. Hibler, Qiuyin Cai, Jirong Long, Zhi Chen, Guoliang Li, Ming Jiang, Lifang Hou, Edmond K. Kabagambe, Bing Zhang, Walter E. Smalley, Todd L. Edwards, Edward L. Giovannucci, Wei Zheng, Qi Dai^*

^*Corresponding author for this work

Preventive Medicine

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

Some studies suggest that the calcium to magnesium ratio intakes modify the associations of calcium or magnesium with risk of colorectal adenoma, adenoma recurrence, and cancer. Parathyroid hormone (PTH) plays a key role in the regulation of homeostasis for both calcium and magnesium. We hypothesized that polymorphisms in PTH and 13 other genes may modify the association between the calcium/magnesium intake ratio and colorectal neoplasia risk. We conducted a two-phase study including 1336 cases and 2891 controls from the Tennessee Colorectal Polyp Study. In Phase I, we identified 19 SNPs that significantly interacted with the calcium/magnesium intake ratio in adenoma risk. In Phase II, rs11022858 in PTH was replicated. In combined analysis of phases I and II, we found high calcium/magnesium intake ratio tended to be associated with a reduced risk of colorectal adenoma (P for trend, 0.040) among those who carried the TT genotype in rs11022858. In stratified analyses, calcium intake (≥ 1000 mg/d) was significantly associated with 64% reduced adenoma risk (OR = 0.36 (95% CI : 0.18–0.74)) among those homozygous for the minor allele (TT genotype) (P for trend, 0.012), but not associated with risk in other genotypes (CC/TC). Conversely, we found that highest magnesium intake was significantly associated with 27% reduced risk (OR = 0.73 (95% CI : 0.54–0.97)) of colorectal adenoma (P for trend, 0.026) among those who possessed the CC/TC genotypes, particularly among those with the TC genotype, whereas magnesium intake was not linked to risk among those with the TT genotype. These findings, if confirmed, will help for the development of personalized prevention strategies for colorectal cancer.

Original language	English (US)
Pages (from-to)	1449-1457
Number of pages	9
Journal	Molecular Carcinogenesis
Volume	55
Issue number	10
DOIs	https://doi.org/10.1002/mc.22387
State	Published - Oct 1 2016

Funding

This study was supported through the US National Center for Complementary and Alternative Medicine grants R01AT004660, Office of Dietary Supplements, National Cancer Institute grants R01CA149633 (to QD) and U01CA182364 (to QD & TLE), as well as parent studies P50CA95103 (to WZ) and R01CA121060 (to WZ) and the American Institute for Cancer Research Grant #08A074 (to QD). The survey and sample processing for the TCPS 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 TLE). We wish to thank Regina Courtney for her excellent laboratory technical support.

Keywords

PTH
calcium
colorectal neoplasia
gene-nutrient interaction
magnesium

ASJC Scopus subject areas

Molecular Biology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/mc.22387

Cite this

Zhu, X., Shrubsole, M. J., Ness, R. M., Hibler, E. A., Cai, Q., Long, J., Chen, Z., Li, G., Jiang, M., Hou, L., Kabagambe, E. K., Zhang, B., Smalley, W. E., Edwards, T. L., Giovannucci, E. L., Zheng, W., & Dai, Q. (2016). Calcium/magnesium intake ratio, but not magnesium intake, interacts with genetic polymorphism in relation to colorectal neoplasia in a two-phase study. Molecular Carcinogenesis, 55(10), 1449-1457. https://doi.org/10.1002/mc.22387

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title = "Calcium/magnesium intake ratio, but not magnesium intake, interacts with genetic polymorphism in relation to colorectal neoplasia in a two-phase study",

abstract = "Some studies suggest that the calcium to magnesium ratio intakes modify the associations of calcium or magnesium with risk of colorectal adenoma, adenoma recurrence, and cancer. Parathyroid hormone (PTH) plays a key role in the regulation of homeostasis for both calcium and magnesium. We hypothesized that polymorphisms in PTH and 13 other genes may modify the association between the calcium/magnesium intake ratio and colorectal neoplasia risk. We conducted a two-phase study including 1336 cases and 2891 controls from the Tennessee Colorectal Polyp Study. In Phase I, we identified 19 SNPs that significantly interacted with the calcium/magnesium intake ratio in adenoma risk. In Phase II, rs11022858 in PTH was replicated. In combined analysis of phases I and II, we found high calcium/magnesium intake ratio tended to be associated with a reduced risk of colorectal adenoma (P for trend, 0.040) among those who carried the TT genotype in rs11022858. In stratified analyses, calcium intake (≥ 1000 mg/d) was significantly associated with 64\% reduced adenoma risk (OR = 0.36 (95\% CI : 0.18–0.74)) among those homozygous for the minor allele (TT genotype) (P for trend, 0.012), but not associated with risk in other genotypes (CC/TC). Conversely, we found that highest magnesium intake was significantly associated with 27\% reduced risk (OR = 0.73 (95\% CI : 0.54–0.97)) of colorectal adenoma (P for trend, 0.026) among those who possessed the CC/TC genotypes, particularly among those with the TC genotype, whereas magnesium intake was not linked to risk among those with the TT genotype. These findings, if confirmed, will help for the development of personalized prevention strategies for colorectal cancer.",

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author = "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 Ming Jiang and Lifang Hou and Kabagambe, \{Edmond K.\} and Bing Zhang and Smalley, \{Walter E.\} and Edwards, \{Todd L.\} and Giovannucci, \{Edward L.\} and Wei Zheng and Qi Dai",

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Zhu, X, Shrubsole, MJ, Ness, RM, Hibler, EA, Cai, Q, Long, J, Chen, Z, Li, G, Jiang, M, Hou, L, Kabagambe, EK, Zhang, B, Smalley, WE, Edwards, TL, Giovannucci, EL, Zheng, W & Dai, Q 2016, 'Calcium/magnesium intake ratio, but not magnesium intake, interacts with genetic polymorphism in relation to colorectal neoplasia in a two-phase study', Molecular Carcinogenesis, vol. 55, no. 10, pp. 1449-1457. https://doi.org/10.1002/mc.22387

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T1 - Calcium/magnesium intake ratio, but not magnesium intake, interacts with genetic polymorphism in relation to colorectal neoplasia in a two-phase study

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 - Jiang, Ming

AU - Hou, Lifang

AU - Kabagambe, Edmond K.

AU - Zhang, Bing

AU - Smalley, Walter E.

AU - Edwards, Todd L.

AU - Giovannucci, Edward L.

AU - Zheng, Wei

AU - Dai, Qi

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Some studies suggest that the calcium to magnesium ratio intakes modify the associations of calcium or magnesium with risk of colorectal adenoma, adenoma recurrence, and cancer. Parathyroid hormone (PTH) plays a key role in the regulation of homeostasis for both calcium and magnesium. We hypothesized that polymorphisms in PTH and 13 other genes may modify the association between the calcium/magnesium intake ratio and colorectal neoplasia risk. We conducted a two-phase study including 1336 cases and 2891 controls from the Tennessee Colorectal Polyp Study. In Phase I, we identified 19 SNPs that significantly interacted with the calcium/magnesium intake ratio in adenoma risk. In Phase II, rs11022858 in PTH was replicated. In combined analysis of phases I and II, we found high calcium/magnesium intake ratio tended to be associated with a reduced risk of colorectal adenoma (P for trend, 0.040) among those who carried the TT genotype in rs11022858. In stratified analyses, calcium intake (≥ 1000 mg/d) was significantly associated with 64% reduced adenoma risk (OR = 0.36 (95% CI : 0.18–0.74)) among those homozygous for the minor allele (TT genotype) (P for trend, 0.012), but not associated with risk in other genotypes (CC/TC). Conversely, we found that highest magnesium intake was significantly associated with 27% reduced risk (OR = 0.73 (95% CI : 0.54–0.97)) of colorectal adenoma (P for trend, 0.026) among those who possessed the CC/TC genotypes, particularly among those with the TC genotype, whereas magnesium intake was not linked to risk among those with the TT genotype. These findings, if confirmed, will help for the development of personalized prevention strategies for colorectal cancer.

AB - Some studies suggest that the calcium to magnesium ratio intakes modify the associations of calcium or magnesium with risk of colorectal adenoma, adenoma recurrence, and cancer. Parathyroid hormone (PTH) plays a key role in the regulation of homeostasis for both calcium and magnesium. We hypothesized that polymorphisms in PTH and 13 other genes may modify the association between the calcium/magnesium intake ratio and colorectal neoplasia risk. We conducted a two-phase study including 1336 cases and 2891 controls from the Tennessee Colorectal Polyp Study. In Phase I, we identified 19 SNPs that significantly interacted with the calcium/magnesium intake ratio in adenoma risk. In Phase II, rs11022858 in PTH was replicated. In combined analysis of phases I and II, we found high calcium/magnesium intake ratio tended to be associated with a reduced risk of colorectal adenoma (P for trend, 0.040) among those who carried the TT genotype in rs11022858. In stratified analyses, calcium intake (≥ 1000 mg/d) was significantly associated with 64% reduced adenoma risk (OR = 0.36 (95% CI : 0.18–0.74)) among those homozygous for the minor allele (TT genotype) (P for trend, 0.012), but not associated with risk in other genotypes (CC/TC). Conversely, we found that highest magnesium intake was significantly associated with 27% reduced risk (OR = 0.73 (95% CI : 0.54–0.97)) of colorectal adenoma (P for trend, 0.026) among those who possessed the CC/TC genotypes, particularly among those with the TC genotype, whereas magnesium intake was not linked to risk among those with the TT genotype. These findings, if confirmed, will help for the development of personalized prevention strategies for colorectal cancer.

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Calcium/magnesium intake ratio, but not magnesium intake, interacts with genetic polymorphism in relation to colorectal neoplasia in a two-phase study

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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