Genetic variation in SLC7A2 interacts with calcium and magnesium intakes in modulating the risk of colorectal polyps.
Genetic variation in SLC7A2 interacts with calcium and magnesium intakes in modulating the risk of colorectal polyps.
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SLC7A2 的遗传变异与钙和镁的摄入量相互作用，调节结直肠息肉的风险。
DOI：
10.1016/j.jnutbio.2017.04.016
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Dai,Qi
中科院分区：
文献类型：
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作者：
Sun,Pin;Zhu,Xiangzhu;Shrubsole,MarthaJ;Ness,ReidM;Hibler,ElizabethA;Cai,Qiuyin;Long,Jirong;Chen,Zhi;Li,Guoliang;Hou,Lifang;Smalley,WalterE;Edwards,ToddL;Giovannucci,Edward;Zheng,Wei;Dai,Qi
溶质载体家族7，成员2(SLC7A2)基因编码一种名为阳离子氨基酸转运蛋白2的蛋白质，它介导精氨酸、赖氨酸和鸟氨酸的转运。l-精氨酸是肿瘤发生发展所必需的，包括在结直肠癌发病机制中的重要作用。此外，以前的研究发现，钙和镁都抑制精氨酸的运输。因此，钙、镁或钙镁摄入量比可能与SLC7A2基因的多态相互作用，从而与结直肠癌相关。我们在田纳西州大肠息肉研究中进行了一项两阶段病例对照研究。在第一阶段中，对725例结直肠腺瘤患者和755例对照组进行了SLC7A2基因23个标记单核苷酸多态性研究。在对607例患者和2113名对照进行的第二阶段研究中，我们重复了第一阶段的重要发现。我们观察到rs2720574与钙镁摄入量比率显著交互作用，与腺瘤，特别是多发性/晚期腺瘤的发病几率相关。在联合分析中，在钙镁摄入量比低于2.78的人群中，携带GC/CC基因的个体比携带GG基因的个体患腺瘤[OR(95%CI)：1.36(1.11-1.68)]和多发/晚期腺瘤[OR(95%CI)：1.68(1.28，2.20)]的几率更高。钙镁摄入量比与rs2720574相互作用的P值对于所有腺瘤为0.002，对于多发性/进展期腺瘤为0.001。在GG基因型者中，高钙镁比与结直肠腺瘤[OR(95%CI)：1.73(1.27-2.36)]和进展性/多发性腺瘤[1.62(1.05-2.50)]相关；而在GC/CC基因型者中，高钙/镁比与结直肠腺瘤[0.64(0.42-0.99)]和进展性/多发性腺瘤[0.55(0.31-1.00)]相关。
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 theSLC7A2gene 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 theSLC7A2gene 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. ThePvalues 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)].