Department of Neurosurgery, Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Exp Biol Med (Maywood). 2013 Sep;238(9):1075-81. doi: 10.1177/1535370213498977. Epub 2013 Aug 23.
Dysregulation of the amino acid transporter SLC7A7 is involved in multiple types of cancer including gliobastoma (GBM), the most malignant form of glioma. We hypothesized that SLC7A7 genetic variants may influence glioma risk. To test this hypothesis, we conducted a case-control study in 736 incident glioma cases and 793 cancer-free controls in a Chinese population by genotyping 22 common single nucleotide polymorphisms in SLC7A7. In single-locus analysis, we found an increased risk was associated with the variant genotypes of rs12888930 (adjusted odds ratio [OR] = 1.25, 95% confidence interval [CI] 1.02-1.54, P = 0.034), rs12433985 (adjusted OR = 1.38, 95%CI = 1.13-1.70), rs2065134 (adjusted OR = 1.43, 95% CI 1.05-1.95) in a dominant genetic model and rs12436190 (adjusted OR = 1.37, 95%CI 1.06-1.77) in a recessive model. Multivariate analysis confirmed that rs12433985 and rs2065134 were significant and independent risk factor for glioma as well as GBM subtype (for rs12433985, OR = 1.21, 95%CI 1.04-1.42, P = 0.016 for all types of gliomas and P = 0.013, OR = 1.30, 95%CI 1.06-1.60 for GBM. For rs2065134, OR = 1.39, 95%CI 1.02-1.89, P = 0.039 for all types of gliomas and OR = 1.66, 95%CI 1.12-2.24, P = 0.011). These results, for the first time, provide suggestive evidence of polymorphisms in SLC7A7 is involved in the aetiology of glioma.
SLC7A7 氨基酸转运蛋白的失调与多种癌症有关，包括胶质母细胞瘤（GBM），这是最恶性的胶质瘤形式。我们假设 SLC7A7 遗传变异可能影响胶质母细胞瘤的风险。为了验证这一假设，我们在中国人群中进行了一项病例对照研究，共纳入 736 例新诊断的胶质母细胞瘤病例和 793 例无癌症对照，通过对 SLC7A7 中 22 个常见的单核苷酸多态性进行基因分型。在单基因座分析中，我们发现 rs12888930（调整后的优势比 [OR] = 1.25，95%置信区间 [CI] 1.02-1.54，P = 0.034）、rs12433985（调整后的 OR = 1.38，95%CI = 1.13-1.70）、rs2065134（调整后的 OR = 1.43，95%CI = 1.05-1.95）在显性遗传模型和 rs12436190（调整后的 OR = 1.37，95%CI = 1.06-1.77）在隐性遗传模型中，变异基因型与风险增加相关。多变量分析证实 rs12433985 和 rs2065134 是胶质母细胞瘤以及胶质母细胞瘤亚型的显著且独立的危险因素（对于 rs12433985，所有类型的胶质母细胞瘤 OR = 1.21，95%CI 1.04-1.42，P = 0.016；GBM 亚型 OR = 1.30，95%CI 1.06-1.60，P = 0.013。对于 rs2065134，所有类型的胶质母细胞瘤 OR = 1.39，95%CI 1.02-1.89，P = 0.039；GBM 亚型 OR = 1.66，95%CI 1.12-2.24，P = 0.011）。这些结果首次提供了 SLC7A7 多态性与胶质母细胞瘤病因相关的提示性证据。
