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  • American Association for Cancer Research (AACR)  (9)
  • Smalley, Walter E.  (9)
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  • American Association for Cancer Research (AACR)  (9)
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  • 1
    Online Resource
    Online Resource
    Abstract 802: Genetic polymorphism in SLC7A2 interacts with calcium:magnesium intake ratio in risk of colorectal neoplasia in a two-phase study
    American Association for Cancer Research (AACR) ; 2016
    In:  Cancer Research Vol. 76, No. 14_Supplement ( 2016-07-15), p. 802-802
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 14_Supplement ( 2016-07-15), p. 802-802
    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 & lt; 0.05. However, rs2720574 significantly interacted with Ca:Mg intake ratio in association with adenoma risk, particularly multiple/advanced adenoma in both the first and second phases. In the combined analysis, among those with a Ca:Mg intake ratio below 2.78, individuals who carried GC/CC genotypes were at a higher risk of adenoma [odds ratio (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. Among those with the GG genotype, a high Ca:Mg ratio was associated with increased risks 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 Ca:Mg ratio was related to reduced risks of colorectal adenoma (0.64(0.42-0.99))and advanced/multiple adenomas (0.55(0.31-1.00)); p(interactions) = 0.002 and 0.0001 for total and advanced/multiple adenomas, respectively. These findings indicate the Ca:Mg ratio, instead of Mg or Ca alone, interacted with SLC7A2 polymorphism in risk of colorectal neoplasia. 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.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2016-802
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
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    detail.hit.zdb_id: 410466-3
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  • 2
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    Online Resource
    Abstract 909: Calcium intake, CASR polymorphisms and phenotype, and the risk of colorectal adenoma: Results from Tennessee Colorectal Polyp Study
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Research Vol. 70, No. 8_Supplement ( 2010-04-15), p. 909-909
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 909-909
    Abstract: Background: A number of cohort studies and randomized trials suggest that high calcium consumption may confer a reduced risk of colorectal cancer. Results, however, have been inconsistent. It is possible that the calcium effect may differ by polymorphisms in the genes involved in calcium regulation. Calcium-sensing receptor (CASR) tightly regulates systemic calcium levels by sensing minor changes in extracellular calcium concentration. Studies have found that CaSR is expressed in the human colon epithelium and regulates epithelial proliferation and differentiation. It was also shown that luminal calcium inhibited colorectal tumors through CaSR. Four studies have thus far investigated the associations of CASR polymorphisms and haplotypes and their interactions with calcium intakes in relation to risk of colorectal cancer or adenoma. However, these studies have generated inconsistent results. Objectives: In the current study, we first screened whether CASR variants or their interactions with calcium intake were associated with urinary calcium phenotype among 233 normal controls. SNPs which were associated with phenotype were further evaluated for their independent association and interaction with calcium intake on colorectal adenoma risk. Methods: Included in the study were participants of the Tennessee Colorectal Polyp Study (TCPS), an ongoing colonoscopy-based case control study conducted in Nashville, TN. Genotyping was performed using the Affymetrix Human Mapping 500K array set for 666 cases and 751 controls. Twenty two tagging single-nucleotide polymorphisms (SNPs) for CASR were analyzed. Linear regression models (SAS MIXED procedure) were used to estimate association between genotypes and urinary calcium level. Multivariate unconditional logistic regression models were used to estimate the odds ratio (OR) and 95% confidence intervals (CI) for each SNP. Multiplicative interactions for gene-diet interactions were evaluated in logistic regression models by using likelihood ratio tests. Results: Eleven SNPs were significantly associated with urinary calcium levels. Among these 11 SNPs, 4 SNPs significantly interacted with calcium intake in association with risk of adenoma. The association of the genotypes with adenoma risk differed by high or low level of calcium intake. We are conducting additional genotyping assays and will present the updated results in the AACR meeting. Conclusions: These findings suggest that some genetic variations in CASR and/or their interactions with dietary calcium intake have significant functional impact on calcium reabsorption, in turn, affect the risk of colorectal adenoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 909.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM10-909
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 3
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    Abstract 2196: Two-phase study of PTH polymorphisms, calcium, magnesium and colorectal adenoma risk
    American Association for Cancer Research (AACR) ; 2014
    In:  Cancer Research Vol. 74, No. 19_Supplement ( 2014-10-01), p. 2196-2196
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 2196-2196
    Abstract: Background: The findings on the associations between intakes of calcium and magnesium with risks of colorectal adenoma and cancer have not been consistent. Previous studies identified substantial inter-person variability in calcium absorption (10-70%). The differences in calcium absorption persist over time and only a small portion of cases can be explained by known factors. Calcium competes with magnesium in many biological activities such as (re)absorption. The polymorphisms in genes related to calcium and magnesium may modify the associations between intakes of calcium and magnesium and risk of colorectal cancer and adenoma. Parathyroid hormone (PTH) is a critical hormone in the regulation of calcium concentration and magnesium in extracellular fluid and plays a key role in (re)absorption of both calcium and magnesium in the gut and kidney. Objectives: We hypothesize that common variants in PTH may modify the associations between calcium and magnesium intake or calcium/magnesium ratio 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 in 728 colorectal adenoma cases and 757 controls and 3 tagging single-nucleotide polymorphisms (SNPs) in the PTH gene were evaluated. SNPs identified as significant in phase I were genotyped in Phase II in an independent set (546 cases and 2062 controls). Dietary nutrient intakes were obtained from a food frequency questionnaire. Multivariate unconditional logistic regression models were used to estimate the odds ratios and 95% confidence intervals for each SNP. Multiplicative interactions were evaluated for gene-diet interactions using likelihood ratio tests. Results: In Phase I of the study, we identified 2 SNPs that significantly interacted with calcium to magnesium (Ca/Mg) intake ratio in association with adenoma risk. In an independent set (Phase II), one of two gene-Ca/Mg ratio interactions was replicated. In the combined analysis, we found that intakes of calcium and magnesium were related to a reduced risk of colorectal adenoma. However, in stratified analysis, magnesium intake was only associated with a reduced risk of adenoma among those with the TC/CC genotype (p for trend, 0.03). Magnesium intake≥320 mg/day was linked to about 40% reduction in risk among those with the TC genotype. On the other hand, calcium intake was only related to a reduced risk for those who carry the TC/TT genotype (p for tend, 0.02). Calcium intake≥1000 mg/day was associated with an over 40% reduction in risk of colorectal adenoma among the TT group. Conclusions: Intakes of calcium and magnesium are linked to reduced risk of adenoma for subsets of populations with different genotypes. Citation Format: Zhu Xiangzhu, Martha J. Shrubsole, Reid M. Ness, Qiuyin Cai, Walter E. Smalley, Todd L. Edwards, Edward Giovannucci, Wei Zheng, Qi Dai. Two-phase study of PTH polymorphisms, calcium, magnesium and colorectal adenoma risk. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2196. doi:10.1158/1538-7445.AM2014-2196
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2014-2196
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2014
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 4
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    Abstract 4478: Erythrocyte magnesium, TRPM7 Thr1482Ile polymorphism, and colorectal adenoma risk
    American Association for Cancer Research (AACR) ; 2012
    In:  Cancer Research Vol. 72, No. 8_Supplement ( 2012-04-15), p. 4478-4478
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 4478-4478
    Abstract: Background: Several epidemiologic studies indicate high intake of magnesium may be related to a reduced risk of colorectal cancer and adenoma. However, results from previous studies have not been consistent. We reported previously the inverse association between dietary magnesium and risk of colorectal adenoma primarily appeared in those who carried at least one Thr1482Ile allele in the transient receptor potential melastatin 7 (TRPM7) gene, which plays an essential role in the homeostasis and sensing of magnesium. Serum magnesium is regulated in a narrow range and previous studies indicate erythrocyte magnesium may be a better biomarker of body magnesium status than serum magnesium. Objective: To examine whether erythrocyte magnesium is associated with adenoma risk and if the association is modified by the Thr1482Ile polymorphism. Design: Included in this nested case-control study were 341adenoma cases and 343 matched polyp-free controls from the Tennessee Colorectal Polyp Study (TCPS), a colonoscopy-based case control study conducted in Nashville, TN. Total erythrocyte magnesium levels were measured using flame atomic absorption spectroscopy. Genotyping assay was performed using the TaqMan OpenArray platform. Multivariate logistic regression models were used to estimate the odds ratio and 95% confidence intervals as a measure of the strength of associations. The association of each genotype with colorectal adenoma risk was evaluated under dominant, recessive and additive models, respectively. Results: Overall erythrocyte magnesium level was not associated with risk of colorectal adenoma. However, erythrocyte magnesium tended to be associated with a reduced risk among those who carried at least one Thr1482Ile allele in the TRPM7 gene (rs8042919), particularly after adjusting for potential confounding factors, such as age, assay batch, family history, and dietary intakes of magnesium and fiber with the ORs (95% CI) of 0.19 (0.05, 0.76) and 0.34 (0.08, 1.49) respectively for the medium and highest tertile of erythrocyte magnesium levels versus the lowest tertile. In addition, among people with erythrocyte magnesium below the median, we found people who carried at least one 1482Ile allele tended to be at an elevated risk of adenoma with an OR (95% CI) of 1.7(0.85, 3.43), compared to those who did not carry the polymorphism; while the corresponding OR (95% CI) was 0.94 (0.49, 1.81) for those who carried at least one Thr1482Ile allele if erythrocyte magnesium was above the median. Conclusions: Our findings indicate the TRPM7 Thr1482Ile polymorphism may interact with erythrocyte magnesium levels in relation to colorectal adenoma risk even after controlling for dietary intake of magnesium. 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 4478. doi:1538-7445.AM2012-4478
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2012-4478
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
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  • 5
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    Abstract 2859: Genetic polymorphisms in the PTH and PTHR1 genes and colorectal adenoma risk
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Research Vol. 70, No. 8_Supplement ( 2010-04-15), p. 2859-2859
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 2859-2859
    Abstract: Background: A number of cohort studies and randomized trials suggest that high calcium consumption may confer a reduced risk of colorectal cancer. Results, however, have been inconsistent. It is possible that the calcium effect may differ by polymorphisms in the genes involved in calcium regulation. Parathyroid hormone (PTH) is a critical hormone in the regulation of calcium concentration in extracellular fluid. The PTH and its receptors (PTHR) play an essential role in calcium homeostasis. Thus far, no study has been conducted to investigate the association of genetic variations in the PTH pathway and risk of colorectal adenoma or cancer. In the present study, we examined single nucleotide polymorphisms (SNPs) in the PTH and PTHR genes and their interaction with calcium intake in relation to risk of colorectal adenoma using data from the Tennessee Colorectal Polyp Study. Methods: Included in the study were participants of the Tennessee Colorectal Polyp study, an ongoing colonoscopy-based case control study conducted in Nashville, TN. Genotyping was performed at Vanderbilt Microarray Shared resource using the Affymetrix Human Mapping 500K array set. Three SNPs in the PTH gene and two SNPs in the PTHR1 were genotyped for 738 colorectal adenoma cases and 776 controls. Hardy-Weinberg equilibrium was assessed for each SNP among controls. The associations of each genotype with colorectal adenoma risk were evaluated under dominant, recessive and additive models, respectively. Multivariate unconditional logistic regression models were used to estimate the odds ratio and 95% confidence intervals for each SNP. Multiplicative interactions were evaluated for gene-diet interactions using likelihood ratio tests. Results: There were no significant differences in selected demographic characteristics and potential confounding factors between the colorectal adenoma case and control groups. All the genotype frequencies for PTH and PTHR1 were in Hardy-Weinberg equilibrium. There were no associations between the PTH genotypes and the risk for colorectal adenoma under dominant, recessive or additive models. One SNP (rs 7652849) in the PTHR1 gene was significantly associated with the risk of colorectal adenoma in both unadjusted model (OR: 1.32; 95%CI: 1.02, 1.71; p = 0.034) and adjusted model (OR: 1.32; 95%CI: 1.00, 1.73; p = 0.047). Furthermore, we found the SNP (rs 936173) in the PTHR1 gene significantly interacted with calcium intake in relation to risk of colorectal cancer (p = 0.046). No significant interactions with calcium intake were observed for the PTH gene. Conclusions: Our results suggest polymorphisms in PTHR1 may contribute to or interact with calcium intake in relation to risk of colorectal adenoma. Although further investigations of the PTHR1 gene polymorphisms on colorectal adenoma risk are required, our findings might provide some new insights into the mechanisms through which calcium reduces colorectal cancer risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2859.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM10-2859
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 6
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    Abstract 4832: High calcium reduces multiple or advanced colorectal adenoma risk by nearly 90% among those with variant alleles in two critical genes in calcium reabsorption.
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Research Vol. 73, No. 8_Supplement ( 2013-04-15), p. 4832-4832
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 4832-4832
    Abstract: Despite the rapidly increasing use of colonoscopy, colorectal cancer still remains the 2nd most common cause of cancer death in the United States. Most of these colorectal cancers arise from adenomas. High calcium consumption has been linked to reduced risks of colorectal adenoma and cancer. However, results from a large clinical trial conducted in the general population were not consistent from those conducted among colorectal adenoma patients. Adenoma patients have a lower intake of calcium than general population. Furthermore, previous studies indicate there is substantial inter-individual variation in the ability to (re)absorb calcium, which is mostly attributed to genetic variation. Thus, we hypothesized that some of the inconsistency in previous studies was due to interactions between calcium and genetic polymorphisms involved in calcium homeostasis. In an NIH R01 project, we conducted a two- phase study to evaluate whether polymorphisms in KCNJ1 and 13 other genes modified the associations between calcium intake and risk of colorectal adenoma. Included in the study were 1818 cases and 3992 controls identified from the Tennessee Colorectal Polyp Study (TCPS), a colonoscopy-based case control study conducted in Nashville, TN. We identified in Phase 1 and replicated in Phase 2 that two polymorphisms in two genes (i.e. one SNP in each gene) significantly modified the associations between calcium intake and colorectal adenoma risk. One gene is potassium inwardly-rectifying channel, subfamily J, member 1 (KCNJ1), which etiologically leads to hereditary familial diseases with impairments in reabsorption for calcium. The p for interaction with the SNP in the KCNJ1 gene remained statistically significant after Bonferroni correction for multiple comparisons (all SNPs in 14 genes). In the combined analysis of these two genes, we found 52% of the study population carry at least one variant allele in one of two genes while 13% of the population carry variant alleles in both genes. We found among those with zero variant alleles in two genes, the highest tertile of calcium intake was not associated with adenoma risk with an OR (95% CI) of 1.06(0.65-1.72). Highest calcium intake tertile was significantly associated with a 39% reduced adenoma risk among those who carry variant allele in one gene (p for trend, 0.046), and with a 69% reduced risk among those with alleles in both genes (p for trend, 0.039). The corresponding reduction in risk with advanced or multiple adenomas increased to 89% (95%CI: 41%-98%) among those with variant alleles in both genes (p for interaction, 5.5×10−5). In summary, high intake of calcium may only protect against colorectal carcinogenesis among those who carry variant alleles in two genes, particularly for those who carry variant alleles in both genes. Citation Format: Xiangzhu Zhu, Martha J. Shrubsole, Reid M. Ness, Qiuyin Cai, Jirong Long, Zhi Chen, Ji Liang, Guoliang Li, Walter E. Smalley, Todd L. Edwards, Edward Giovannucci, Wei Zheng, Qi Dai. High calcium reduces multiple or advanced colorectal adenoma risk by nearly 90% among those with variant alleles in two critical genes in calcium reabsorption. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4832. doi:10.1158/1538-7445.AM2013-4832
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2013-4832
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
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    detail.hit.zdb_id: 1432-1
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  • 7
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    Abstract 1674: Two phase study of KCNJ1 polymorphisms, calcium, magnesium and colorectal adenoma risk, results from the Tennessee Colorectal Polyp Study
    American Association for Cancer Research (AACR) ; 2012
    In:  Cancer Research Vol. 72, No. 8_Supplement ( 2012-04-15), p. 1674-1674
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 1674-1674
    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
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2012-1674
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 8
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    Abstract 3763: Calcium intake, CABP1 polymorphisms, and the risk of colorectal adenoma: Results from Tennessee Colorectal Polyp Study
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. 3763-3763
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 3763-3763
    Abstract: Background: High calcium consumption may confer a reduced risk of colorectal adenoma and cancer. This effect could differ by polymorphisms in the genes involved in calcium regulation. The calcium binding protein 1(CABP1) gene encodes a calbindin-D9k protein, an important component of calcium mediated cellular signal transduction. CABP1 express primarily in intestine, and increased levels of Calbindin-D9k in intestine were found to be correlated with calcium hyperabsorption. A recent study found that deletion of CABP1 and another gene had a significant effect on calcium processing under calcium-deficient conditions. These findings suggest the variations in CABP1 expression in intestine may explain some of the variability in calcium absorption. However, so far no study has evaluated genetic variations in CABP1 with the risk of colorectal adenoma. Objectives: In the current study, we first screened whether CABP1 variants or their interactions with calcium intake were associated with urinary calcium among 256 normal controls. Further, single-nucleotide polymorphisms (SNPs) were evaluated for their independent association and interactions with calcium intake in relation to colorectal adenoma risk. Methods: Included in the study were 958 adenoma cases and 909 controls from the Tennessee Colorectal Polyp Study (TCPS), an ongoing colonoscopy-based case-control study conducted in Nashville, TN. Genotyping was performed using the Affymetrix Human Mapping 500K array set. Seven tagging SNPs in CABP1 were analyzed. Linear regression models were used to estimate the association between genotypes and urinary calcium level. Multivariate unconditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI). Multiplicative interactions for gene-diet interactions were evaluated in logistic regression models by using likelihood ratio tests. Results: Although no SNPs were observed to be associated with urinary calcium levels, one SNP (rs7956304) was found to be significantly associated with risk of adenoma. In comparison to participants with the GG genotype, participants with GA had higher risk of colorectal adenoma (OR=1.29, 95% CI 1.03-1.61, P=0.027), while participants with the AA genotype had no appreciable difference in risk (OR=0.82, 95% CI 0.50-1.35, P=0.428). This SNP was not observed to interact with calcium intake. Conclusions: These findings suggest that genetic variations in CABP1 may affect the risk of colorectal adenoma. To the best of our knowledge, this study is the first to evaluate CABP1 polymorphisms in relation to the risk of adenoma. Our finding of a significant association is promising; however, the finding should be confirmed in future studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3763. doi:10.1158/1538-7445.AM2011-3763
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2011-3763
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 9
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    Abstract LB-452: Genetic polymorphisms in the TRPM7 gene and colorectal adenoma risk
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. LB-452-LB-452
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. LB-452-LB-452
    Abstract: Background: Several epidemiologic studies suggest that high magnesium intake is associated with reduced risk of colorectal cancer or colorectal adenoma. Results, however, have been inconsistent. Ionized magnesium (Mg2+) counters the action of ionized calcium (Ca2+) in many physiologic activities. We previously reported that the associations between intakes of magnesium, calcium or calcium/magnesium ratio with risk of colorectal polyp were modified by the common Thr1482Ile polymorphism in the gene for the transient receptor potential melastatin 7 (TRPM7), which is a ubiquitously expressed constitutive ion channel with a higher affinity for Mg2+ than for Ca2+ and plays a central role in magnesium homeostasis and magnesium (re)absorption pathways. Except for our earlier study, no other study has investigated these possible gene-nutrient interactions in the etiology of colorectal adenoma or cancer. In the present study, we examined single nucleotide polymorphisms (SNPs) in the TRPM7 gene and their interaction with calcium and magnesium intake or calcium/magnesium ratio in relation to risk of colorectal adenoma using data from the Tennessee Colorectal Polyp Study. Methods: Included in the study were participants of the Tennessee Colorectal Polyp study, an ongoing colonoscopy-based case control study conducted in Nashville, TN. Genotyping was performed at Vanderbilt Microarray Shared Resource using the Affymetrix Genome-Wide Human SNP Array 5.0. Sixteen SNPs in the TRPM7 gene were genotyped for 958 colorectal adenoma cases and 909 controls. Hardy-Weinberg equilibrium was assessed for each SNP among controls. The associations of each genotype with colorectal adenoma risk were evaluated under dominant, recessive and additive models, respectively. Multivariate unconditional logistic regression models were used to estimate the odds ratio and 95% confidence intervals for each SNP. Multiplicative interactions were evaluated for gene-diet interactions using likelihood ratio tests. Results: All the genotype frequencies for the TRPM7 were in Hardy-Weinberg equilibrium. Of the sixteen SNPs, Four SNPs were significantly associated with risk of colorectal adenoma whereas six SNPs significantly interacted with dietary calcium intake or the ratio of dietary calcium to magnesium intake (five SNPs with calcium and six with the ratio) in relation to risk of colorectal adenoma. The two sets of SNPs were not in strong linkage disequilibrium (LD). However, either three of the four associated SNPs or all of the six interacting SNPs were in strong LD with one another respectively. No significant interactions with magnesium intake were observed. Conclusions: Our results suggest that genetic polymorphisms in the TRPM7 gene, particularly their interactions with calcium or calcium/magnesium ratio, contribute to risk of colorectal adenoma. Further replications in large-scale studies are ongoing. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-452. doi:10.1158/1538-7445.AM2011-LB-452
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2011-LB-452
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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