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Yuan Yuan - One of the best experts on this subject based on the ideXlab platform.

  • abstract 5304 a serological biopsy using five stomach specific circulating biomarkers for gastric cancer risk assessment a multi Phase Study
    Cancer Research, 2017
    Co-Authors: Huakang Tu, Yuehua Gong, Xifeng Wu, Jingjing Jing, Roberd M Bostick, Qian Xu, Xiao Dong, Yuan Yuan
    Abstract:

    Objective: We aimed to assess a serological biopsy using five stomach-specific circulating biomarkers—pepsinogen I (PGI), PGII, PGI/II ratio, anti-Helicobacter pylori (H. pylori) antibody, and gastrin-17 (G-17)—for identifying high-risk individuals and predicting risk of developing gastric cancer (GC). Methods: Among 12112 participants with prospective follow-up from an ongoing population-based screening program using both serology and gastroscopy in China, we conducted a multi-Phase Study involving a cross-sectional analysis, a follow-up analysis, and an integrative risk prediction modeling analysis. Results: In the cross-sectional analysis, the five biomarkers (especially PGII, the PGI/II ratio, and H. pylori sero-positivity) were associated with the presence of precancerous gastric lesions or GC at enrollment. In the follow-up analysis, low PGI levels and PGI/II ratios were associated with higher risk of developing GC, and both low ( 4.7 pmol/L) G-17 levels were associated with higher risk of developing GC, suggesting a J-shaped association. In the risk prediction modeling analysis, the five biomarkers combined yielded a C statistic of 0.801 (95% CI=0.787-0.815) and improved prediction beyond traditional risk factors (C statistic from 0.580 to 0.811, P Conclusions: A serological biopsy composed of the five stomach-specific circulating biomarkers could be used to identify high-risk individuals for further diagnostic gastroscopy, and to stratify individuals’ risk of developing GC and thus to guide targeted screening/precision prevention. Citation Format: Huakang Tu, Liping Sun, Xiao Dong, Yuehua Gong, Qian Xu, Jingjing Jing, Roberd M. Bostick, Xifeng Wu, Yuan Yuan. A serological biopsy using five stomach-specific circulating biomarkers for gastric cancer risk assessment: a multi-Phase Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5304. doi:10.1158/1538-7445.AM2017-5304

  • a serological biopsy using five stomach specific circulating biomarkers for gastric cancer risk assessment a multi Phase Study
    The American Journal of Gastroenterology, 2017
    Co-Authors: Huakang Tu, Yuehua Gong, Xifeng Wu, Jingjing Jing, Roberd M Bostick, Qian Xu, Xiao Dong, Yuan Yuan
    Abstract:

    A Serological Biopsy Using Five Stomach-Specific Circulating Biomarkers for Gastric Cancer Risk Assessment: A Multi-Phase Study

Kevin D. Mullen - One of the best experts on this subject based on the ideXlab platform.

  • role of fresh frozen plasma infusion in correction of coagulopathy of chronic liver disease a dual Phase Study
    The American Journal of Gastroenterology, 2003
    Co-Authors: Wael Youssef, Timothy Beddow, Srinivasan Dasarathy, Fernando Salazar, Kevin D. Mullen
    Abstract:

    OBJECTIVE: Fresh frozen plasma infusions are commonly used to correct the prolonged prothrombin time in patients with advanced chronic liver disease. The aim of this Study was to establish how frequently this treatment is effective in correcting this coagulopathy. METHODS: A split retrospective-prospective Study design was employed. In the retrospective series, 80 patients were identified with prolongation of the prothrombin time who received fresh frozen plasma infusions. In the prospective arm, 20 patients were included. All patients had confirmed chronic liver disease and showed no response to vitamin K injections. None of the patients had evidence of disseminated intravascular coagulation. The indications for infusion of fresh frozen plasma, number of units administered, complications, and percentage of patients who corrected their prothrombin time to less than 3 s longer than control time were recorded. RESULTS: The majority of patients (75%) received 2-4 units of fresh frozen plasma. The mean prothrombin time was numerically improved by the infusion of 2-6 units of fresh frozen plasma. However, using correction to less than 3 s longer than control time as an endpoint, only 12.5% of the retrospective and 10% of the prospective Study groups respectively had correction of their coagulopathy. Only one complication of infusion of plasma was noted during the course of the Study. CONCLUSIONS: Our results reiterate previous observations made more than 45 yr ago, that fresh frozen plasma infusions using the number of units commonly employed in clinical practice infrequently correct the coagulopathy of patients with chronic liver disease. Higher volumes (6 or more units) may be more effective but are rarely employed.

  • role of fresh frozen plasma infusion in correction of coagulopathy of chronic liver disease a dual Phase Study
    The American Journal of Gastroenterology, 2003
    Co-Authors: Wael Youssef, Timothy Beddow, Srinivasan Dasarathy, Fernando Salazar, Kevin D. Mullen
    Abstract:

    Role of Fresh Frozen Plasma Infusion in Correction of Coagulopathy of Chronic Liver Disease: A Dual Phase Study

Martha J Shrubsole - One of the best experts on this subject based on the ideXlab platform.

  • interactions between calcium intake and polymorphisms in genes essential for calcium reabsorption and risk of colorectal neoplasia in a two Phase Study
    Molecular Carcinogenesis, 2017
    Co-Authors: Martha J Shrubsole, Reid M Ness, Xiangzhu Zhu, Elizabeth A. Hibler, Qiuyin Cai, Jing Zhao, Jirong Long
    Abstract:

    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 (P interaction = 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 per day. These findings, if confirmed, may provide a new avenue for the personalized prevention of colorectal adenoma and cancer. This article is protected by copyright. All rights reserved

  • calcium magnesium intake ratio but not magnesium intake interacts with genetic polymorphism in relation to colorectal neoplasia in a two Phase Study
    Molecular Carcinogenesis, 2016
    Co-Authors: Xiangzhu Zhu, Martha J Shrubsole, Reid M Ness, Jirong Long, Zhi Chen, Elizabeth A. Hibler, Qiuyin Cai, Ming Jiang, Lifang Hou, Edmond K Kabagambe
    Abstract:

    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. © 2015 Wiley Periodicals, Inc.

  • abstract 802 genetic polymorphism inslc7a2interacts with calcium magnesium intake ratio in risk of colorectal neoplasia in a two Phase Study
    Cancer Research, 2016
    Co-Authors: Xiangzhu Zhu, Martha J Shrubsole, Reid M Ness, Jirong Long, Zhi Chen, Elizabeth A. Hibler, Qiuyin Cai, Lifang Hou, Pin Sun, Walter E Smalley
    Abstract:

    Colorectal cancer (CRC) remains the third most common cancer in men and the second in women worldwide; thus, preventive strategies for CRC are critically needed. 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 CRC pathogenesis. Furthermore, previous studies found both calcium (Ca) and magnesium (Mg) inhibit the transport of arginine. Thus, Ca, Mg or Ca:Mg intake ratio may interact with polymorphisms in the SLC7A2 gene in risk of CRC. To test this hypothesis, we conducted a two-Phase case-control Study within the Tennessee Colorectal Polyps Study (TCPS) among participants who completed a semi-quantitative 108-item food frequency questionnaire. In the first Phase, 23 tagging single-nucleotide polymorphisms (SNPs) in the SLC7A2 gene were analyzed for 725 colorectal adenoma cases and 755 controls. In the second Phase conducted in an independent set of 607 cases and 2113 controls, we evaluated for replicationthe significant findings from the first Phase. We observed that no SNPs in SLC7A2 were significantly associated with the risk of colorectal adenoma at P Citation Format: Xiangzhu Zhu, Pin Sun, 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. Genetic polymorphism in SLC7A2 interacts with calcium:magnesium intake ratio in risk of colorectal neoplasia in a two-Phase Study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 802.

  • calcium intake and ion transporter genetic polymorphisms interact in human colorectal neoplasia risk in a 2 Phase Study
    Journal of Nutrition, 2014
    Co-Authors: Ji Liang, Dawn M Wiese, Martha J Shrubsole, Reid M Ness, Waltersmalley E Smalley, Jirong Long, Bing Zhang, Zhi Chen, Todd L Edwards
    Abstract:

    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 3 10 24 for all adenoma and 5 3 10 23 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 Pvalues for interactions between calcium intake and combined SNPs from the KCNJ1 and SLC12A1 genes were 7.5 3 10 25 for adenoma and 9.9 3 10 25 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. J. Nutr. doi: 10.3945/jn.114.196709.

  • abstract 1674 two Phase Study of kcnj1 polymorphisms calcium magnesium and colorectal adenoma risk results from the tennessee colorectal polyp Study
    Cancer Research, 2012
    Co-Authors: Martha J Shrubsole, Reid M Ness, Todd L Edwards, Xinqing Deng, Waltersmalley E Smalley, Jirong Long, Zhi Chen, Wei Zheng
    Abstract:

    Background: Previous studies generated inconsistent results on the associations between intakes of calcium and magnesium with risk of colorectal adenoma and cancer. It is possible that some of the inconsistency is due to a modifying effect by genetic polymorphisms involved in calcium and magnesium homeostasis. The KCNJ1 gene encodes the Inward-rectifier potassium channel (ROMK). ROMK plays an essential role in the homeostasis of potassium, which is critical for the reabsorption of calcium and magnesium. Objectives: We hypothesize that common variants in KCNJ1 may modify the associations between intakes of calcium and/or magnesium and risk of colorectal adenoma risk. Methods: Included were participants of the Tennessee Colorectal Polyp Study (TCPS), a colonoscopy-based case control Study conducted in Nashville, TN. In the Phase I Study, genotyping was performed using the Affymetrix Human Mapping 500K array set in 958 colorectal adenoma cases and 909 controls and 13 tagging single-nucleotide polymorphisms (SNPs) in the KCNJ1 gene were evaluated. SNPs identified as significant in Phase I were genotyped in Phase II in an independent set (860 cases and 3083 controls). Results: In Phase I, 1 tagging SNP was significantly associated with adenoma risk and 8 SNPs were interacted significantly with calcium or magnesium intake in risk of colorectal adenoma. In Phase II, only 1 of the 9 SNPs significantly interacted with calcium and magnesium intakes in relation to colorectal adenoma although the genotype per se was not directly associated with the risk. In combined analysis, the p value for the interaction between the SNP and calcium intake was 0.00015 and it remained statistically significant after Bonferroni correction for multiple comparisons. In stratified analyses by levels of calcium and magnesium (above or below RDA levels), we found adenoma risk significantly increased for those who with at least 1 variant allele and whose intake levels of calcium and magnesium were below the RDA levels, with ORs (95% CI) of 1.35 (1.10, 1.67) and 1.43 (1.08, 1.89) respectively, compared to those who did not possess the variant allele. The corresponding ORs (95% CI) increased to 1.84 (1.33, 2.53) and 2.30 (1.53, 3.46), respectively, multiple adenomas versus controls. Conclusions: In this two-stage analysis, we found no overall association of adenoma with KCNJ1 genotype. However, common KCNJ1 variants significantly interacted with intakes of calcium and magnesium in risk of colorectal adenoma, particular for multiple adenomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1674. doi:1538-7445.AM2012-1674

Xiangzhu Zhu - One of the best experts on this subject based on the ideXlab platform.

  • interactions between calcium intake and polymorphisms in genes essential for calcium reabsorption and risk of colorectal neoplasia in a two Phase Study
    Molecular Carcinogenesis, 2017
    Co-Authors: Martha J Shrubsole, Reid M Ness, Xiangzhu Zhu, Elizabeth A. Hibler, Qiuyin Cai, Jing Zhao, Jirong Long
    Abstract:

    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 (P interaction = 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 per day. These findings, if confirmed, may provide a new avenue for the personalized prevention of colorectal adenoma and cancer. This article is protected by copyright. All rights reserved

  • calcium magnesium intake ratio but not magnesium intake interacts with genetic polymorphism in relation to colorectal neoplasia in a two Phase Study
    Molecular Carcinogenesis, 2016
    Co-Authors: Xiangzhu Zhu, Martha J Shrubsole, Reid M Ness, Jirong Long, Zhi Chen, Elizabeth A. Hibler, Qiuyin Cai, Ming Jiang, Lifang Hou, Edmond K Kabagambe
    Abstract:

    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. © 2015 Wiley Periodicals, Inc.

  • abstract 802 genetic polymorphism inslc7a2interacts with calcium magnesium intake ratio in risk of colorectal neoplasia in a two Phase Study
    Cancer Research, 2016
    Co-Authors: Xiangzhu Zhu, Martha J Shrubsole, Reid M Ness, Jirong Long, Zhi Chen, Elizabeth A. Hibler, Qiuyin Cai, Lifang Hou, Pin Sun, Walter E Smalley
    Abstract:

    Colorectal cancer (CRC) remains the third most common cancer in men and the second in women worldwide; thus, preventive strategies for CRC are critically needed. 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 CRC pathogenesis. Furthermore, previous studies found both calcium (Ca) and magnesium (Mg) inhibit the transport of arginine. Thus, Ca, Mg or Ca:Mg intake ratio may interact with polymorphisms in the SLC7A2 gene in risk of CRC. To test this hypothesis, we conducted a two-Phase case-control Study within the Tennessee Colorectal Polyps Study (TCPS) among participants who completed a semi-quantitative 108-item food frequency questionnaire. In the first Phase, 23 tagging single-nucleotide polymorphisms (SNPs) in the SLC7A2 gene were analyzed for 725 colorectal adenoma cases and 755 controls. In the second Phase conducted in an independent set of 607 cases and 2113 controls, we evaluated for replicationthe significant findings from the first Phase. We observed that no SNPs in SLC7A2 were significantly associated with the risk of colorectal adenoma at P Citation Format: Xiangzhu Zhu, Pin Sun, 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. Genetic polymorphism in SLC7A2 interacts with calcium:magnesium intake ratio in risk of colorectal neoplasia in a two-Phase Study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 802.

Jirong Long - One of the best experts on this subject based on the ideXlab platform.

  • interactions between calcium intake and polymorphisms in genes essential for calcium reabsorption and risk of colorectal neoplasia in a two Phase Study
    Molecular Carcinogenesis, 2017
    Co-Authors: Martha J Shrubsole, Reid M Ness, Xiangzhu Zhu, Elizabeth A. Hibler, Qiuyin Cai, Jing Zhao, Jirong Long
    Abstract:

    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 (P interaction = 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 per day. These findings, if confirmed, may provide a new avenue for the personalized prevention of colorectal adenoma and cancer. This article is protected by copyright. All rights reserved

  • calcium magnesium intake ratio but not magnesium intake interacts with genetic polymorphism in relation to colorectal neoplasia in a two Phase Study
    Molecular Carcinogenesis, 2016
    Co-Authors: Xiangzhu Zhu, Martha J Shrubsole, Reid M Ness, Jirong Long, Zhi Chen, Elizabeth A. Hibler, Qiuyin Cai, Ming Jiang, Lifang Hou, Edmond K Kabagambe
    Abstract:

    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. © 2015 Wiley Periodicals, Inc.

  • abstract 802 genetic polymorphism inslc7a2interacts with calcium magnesium intake ratio in risk of colorectal neoplasia in a two Phase Study
    Cancer Research, 2016
    Co-Authors: Xiangzhu Zhu, Martha J Shrubsole, Reid M Ness, Jirong Long, Zhi Chen, Elizabeth A. Hibler, Qiuyin Cai, Lifang Hou, Pin Sun, Walter E Smalley
    Abstract:

    Colorectal cancer (CRC) remains the third most common cancer in men and the second in women worldwide; thus, preventive strategies for CRC are critically needed. 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 CRC pathogenesis. Furthermore, previous studies found both calcium (Ca) and magnesium (Mg) inhibit the transport of arginine. Thus, Ca, Mg or Ca:Mg intake ratio may interact with polymorphisms in the SLC7A2 gene in risk of CRC. To test this hypothesis, we conducted a two-Phase case-control Study within the Tennessee Colorectal Polyps Study (TCPS) among participants who completed a semi-quantitative 108-item food frequency questionnaire. In the first Phase, 23 tagging single-nucleotide polymorphisms (SNPs) in the SLC7A2 gene were analyzed for 725 colorectal adenoma cases and 755 controls. In the second Phase conducted in an independent set of 607 cases and 2113 controls, we evaluated for replicationthe significant findings from the first Phase. We observed that no SNPs in SLC7A2 were significantly associated with the risk of colorectal adenoma at P Citation Format: Xiangzhu Zhu, Pin Sun, 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. Genetic polymorphism in SLC7A2 interacts with calcium:magnesium intake ratio in risk of colorectal neoplasia in a two-Phase Study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 802.

  • calcium intake and ion transporter genetic polymorphisms interact in human colorectal neoplasia risk in a 2 Phase Study
    Journal of Nutrition, 2014
    Co-Authors: Ji Liang, Dawn M Wiese, Martha J Shrubsole, Reid M Ness, Waltersmalley E Smalley, Jirong Long, Bing Zhang, Zhi Chen, Todd L Edwards
    Abstract:

    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 3 10 24 for all adenoma and 5 3 10 23 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 Pvalues for interactions between calcium intake and combined SNPs from the KCNJ1 and SLC12A1 genes were 7.5 3 10 25 for adenoma and 9.9 3 10 25 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. J. Nutr. doi: 10.3945/jn.114.196709.

  • abstract 1674 two Phase Study of kcnj1 polymorphisms calcium magnesium and colorectal adenoma risk results from the tennessee colorectal polyp Study
    Cancer Research, 2012
    Co-Authors: Martha J Shrubsole, Reid M Ness, Todd L Edwards, Xinqing Deng, Waltersmalley E Smalley, Jirong Long, Zhi Chen, Wei Zheng
    Abstract:

    Background: Previous studies generated inconsistent results on the associations between intakes of calcium and magnesium with risk of colorectal adenoma and cancer. It is possible that some of the inconsistency is due to a modifying effect by genetic polymorphisms involved in calcium and magnesium homeostasis. The KCNJ1 gene encodes the Inward-rectifier potassium channel (ROMK). ROMK plays an essential role in the homeostasis of potassium, which is critical for the reabsorption of calcium and magnesium. Objectives: We hypothesize that common variants in KCNJ1 may modify the associations between intakes of calcium and/or magnesium and risk of colorectal adenoma risk. Methods: Included were participants of the Tennessee Colorectal Polyp Study (TCPS), a colonoscopy-based case control Study conducted in Nashville, TN. In the Phase I Study, genotyping was performed using the Affymetrix Human Mapping 500K array set in 958 colorectal adenoma cases and 909 controls and 13 tagging single-nucleotide polymorphisms (SNPs) in the KCNJ1 gene were evaluated. SNPs identified as significant in Phase I were genotyped in Phase II in an independent set (860 cases and 3083 controls). Results: In Phase I, 1 tagging SNP was significantly associated with adenoma risk and 8 SNPs were interacted significantly with calcium or magnesium intake in risk of colorectal adenoma. In Phase II, only 1 of the 9 SNPs significantly interacted with calcium and magnesium intakes in relation to colorectal adenoma although the genotype per se was not directly associated with the risk. In combined analysis, the p value for the interaction between the SNP and calcium intake was 0.00015 and it remained statistically significant after Bonferroni correction for multiple comparisons. In stratified analyses by levels of calcium and magnesium (above or below RDA levels), we found adenoma risk significantly increased for those who with at least 1 variant allele and whose intake levels of calcium and magnesium were below the RDA levels, with ORs (95% CI) of 1.35 (1.10, 1.67) and 1.43 (1.08, 1.89) respectively, compared to those who did not possess the variant allele. The corresponding ORs (95% CI) increased to 1.84 (1.33, 2.53) and 2.30 (1.53, 3.46), respectively, multiple adenomas versus controls. Conclusions: In this two-stage analysis, we found no overall association of adenoma with KCNJ1 genotype. However, common KCNJ1 variants significantly interacted with intakes of calcium and magnesium in risk of colorectal adenoma, particular for multiple adenomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1674. doi:1538-7445.AM2012-1674