Department of Occupational Health and Toxicology, School of Public Health, Fudan University, Shanghai, China 200032.
Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37203; Geriatric, Research, Education and Clinical Center (GRECC), Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37212.
J Nutr Biochem. 2017 Sep;47:35-40. doi: 10.1016/j.jnutbio.2017.04.016. Epub 2017 May 5.
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 the SLC7A2 gene 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 the SLC7A2 gene 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. The P values 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)].
溶质载体家族 7 成员 2（SLC7A2）基因编码一种称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-精氨酸对于癌症的发展和进展是必要的，包括在结直肠癌发病机制中起着重要作用。此外，先前的研究发现钙和镁都能抑制精氨酸的转运。因此，钙、镁或钙：镁摄入量的比值可能与 SLC7A2 基因中的多态性相互作用，与结直肠癌有关。我们在田纳西州结直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，纳入了 SLC7A2 基因中的 23 个标记单核苷酸多态性，用于 725 例结直肠腺瘤病例和 755 例对照。在第二阶段，在一组 607 例病例和 2113 例对照中进行了独立研究，我们复制了第一阶段的显著发现。我们观察到 rs2720574 与钙：镁摄入量比值显著相互作用，与腺瘤的几率相关，特别是多发性/高级别腺瘤。在联合分析中，在钙：镁摄入量比值低于 2.78 的人群中，携带 GC/CC 基因型的个体显示出更高的腺瘤发病几率[比值比（95%可信区间）：1.36（1.11-1.68）]和多发性/高级别腺瘤[比值比（95%可信区间）：1.68（1.28, 2.20）]，而携带 GG 基因型的个体则较低。钙：镁摄入量比值与 rs2720574 之间的交互作用 P 值均<.001。在携带 GG 基因型的个体中，高钙：镁比值与结直肠腺瘤的发病几率增加相关[比值比（95%可信区间）：1.73（1.27-2.36）]和高级/多发性腺瘤[1.62（1.05-2.50）]，而在携带 GC/CC 基因型的个体中，高钙：镁比值与结直肠腺瘤的发病几率降低相关[0.64（0.42-0.99）]和高级/多发性腺瘤[0.55（0.31-1.00）]。
