TY - JOUR
T1 - Interactions between calcium intake and polymorphisms in genes essential for calcium reabsorption and risk of colorectal neoplasia in a two-phase study
AU - Zhao, Jing
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 - Jiang, Ming
AU - Kabagambe, Edmond K.
AU - Zhang, Bing
AU - Hou, Lifang
AU - Smalley, Walter E.
AU - Edwards, Todd L.
AU - Giovannucci, Edward L.
AU - Zheng, Wei
AU - Dai, Qi
N1 - Funding Information:
This study was supported through the US National Center for Complementary and Alternative Medicine grants (R01AT004660 to Q.D.), Office of Dietary Supplements (to Q.D.), as well as parent studies (P50CA95103 and R01CA121060 to W.Z.), and the American Institute for Cancer Research Grant (#08A074 to Q.D.). 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 T.L.E.). Sample preparation and genotyping assays at Vanderbilt were conducted at the Survey and Biospecimen Shared Resources and Vanderbilt Microarray Shared Resource, which are supported in part by Vanderbilt-Ingram Cancer Center (P30 CA068485). The efforts for Drs. Zhao, Zhu and Dai were partially supported by R01 CA149633 and U01 CA182364. We wish to thank Regina Courtney for her excellent laboratory technical support. J.Z., X.Z., Q.D. designed and drafted the manuscript. J.Z., X.Z. carried out the statistical analysis. M.J.S., T.L.E., Z. C., R.M.N., W.E.S. and W.Z. contributed to acquisition of data and human specimens. Q.C., J.L., T.L.E. contributed to the genotyping. All authors contributed to data interpretation, and the critical review of the final manuscript. All authors read and approved the final version of the manuscript. This study was supported through the US National Center for Complementary and Alternative Medicine grants (R01AT004660 to Q.D.), Office of Dietary Supplements (to Q.D.), as well as parent studies (P50CA95103 and R01CA121060 to W.Z.), and the American Institute for Cancer Research Grant (#08A074 to Q.D.). 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 T.L.E.). Sample preparation and genotyping assays at Vanderbilt were conducted at the Survey and Biospecimen Shared Resources and Vanderbilt Microarray Shared Resource, which are supported in part by Vanderbilt-Ingram Cancer Center (P30 CA068485). The efforts for Drs. Zhao, Zhu and Dai were partially supported by R01 CA149633 and U01 CA182364.
Publisher Copyright:
© 2017 Wiley Periodicals, Inc.
PY - 2017/10
Y1 - 2017/10
N2 - The SLC8A1 (solute carrier family 8, member 1) gene, encoding Na+/Ca2+ exchanger, is essential in regulating calcium reabsorption and homeostasis. Calcium homeostasis plays a key role in cell proliferation and apoptosis. We hypothesized that polymorphisms in five calcium-regulating genes (SLC8A1, ATP2B1, CALB1, CALB2, and CABP1) interact with calcium intake in relation to the risk of colorectal neoplasia. A two-phase (discovery and replication) study was conducted within the Tennessee Colorectal Polyp Study, including a total of 1275 cases and 2811 controls. In Phase I, we identified six out of 135 SNPs that significantly interacted with calcium intake in relation to adenoma risk. In Phase II, the calcium intake by rs4952490 (SLC8A1) interaction was replicated (Pinteraction = 0.048). We found an inverse association between calcium intake (1000-2000 mg/day) and colorectal adenomas, particularly for multiple/advanced adenomas, among the G-allele carriers but not among homozygous carriers of the common variant (A) in rs4952490. In the joint analysis of SLC8A1, KCNJ1, and SLC12A1 SNPs, carriers of variant alleles in at least two genes and with calcium intake above the DRI (1000 mg/day) were approximately 30-57% less likely to have adenomas than those whose calcium intake was below the DRI. The association was stronger for multiple/advanced adenomas. No association was found among those who did not carry any variant alleles in these genes when calcium intake was below 2500 mg/day. These findings, if confirmed, may provide a new avenue for the personalized prevention of colorectal adenoma and cancer.
AB - The SLC8A1 (solute carrier family 8, member 1) gene, encoding Na+/Ca2+ exchanger, is essential in regulating calcium reabsorption and homeostasis. Calcium homeostasis plays a key role in cell proliferation and apoptosis. We hypothesized that polymorphisms in five calcium-regulating genes (SLC8A1, ATP2B1, CALB1, CALB2, and CABP1) interact with calcium intake in relation to the risk of colorectal neoplasia. A two-phase (discovery and replication) study was conducted within the Tennessee Colorectal Polyp Study, including a total of 1275 cases and 2811 controls. In Phase I, we identified six out of 135 SNPs that significantly interacted with calcium intake in relation to adenoma risk. In Phase II, the calcium intake by rs4952490 (SLC8A1) interaction was replicated (Pinteraction = 0.048). We found an inverse association between calcium intake (1000-2000 mg/day) and colorectal adenomas, particularly for multiple/advanced adenomas, among the G-allele carriers but not among homozygous carriers of the common variant (A) in rs4952490. In the joint analysis of SLC8A1, KCNJ1, and SLC12A1 SNPs, carriers of variant alleles in at least two genes and with calcium intake above the DRI (1000 mg/day) were approximately 30-57% less likely to have adenomas than those whose calcium intake was below the DRI. The association was stronger for multiple/advanced adenomas. No association was found among those who did not carry any variant alleles in these genes when calcium intake was below 2500 mg/day. These findings, if confirmed, may provide a new avenue for the personalized prevention of colorectal adenoma and cancer.
KW - KCNJ1
KW - SLC12A1
KW - SLC8A1
KW - colorectal neoplasia
KW - gene-calcium interaction
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UR - http://www.scopus.com/inward/citedby.url?scp=85021201982&partnerID=8YFLogxK
U2 - 10.1002/mc.22678
DO - 10.1002/mc.22678
M3 - Article
C2 - 28544176
AN - SCOPUS:85021201982
VL - 56
SP - 2258
EP - 2266
JO - Molecular Carcinogenesis
JF - Molecular Carcinogenesis
SN - 0899-1987
IS - 10
ER -