Department of Intensive Care Unite, The Third Affiliated Hospital to Nantong University, 585 Xing Yuan North Road, 214041 Wuxi, People's Republic of China.
Breast Cancer Res Treat. 2011 Jul;128(2):527-34. doi: 10.1007/s10549-011-1365-x. Epub 2011 Feb 4.
Activated Leukocyte Cell Adhesion Molecules (ALCAM, also called CD166, MEMD) are cell surface immunoglobulins that are considered to be prognostic markers for breast cancer. CD166/ALCAM has gained increasing attention because of its significant association with tumor progression and the metastatic spread of breast cancer. Two polymorphisms have been identified in the CD166/ALCAM gene: 5'UTR C/T (rs6437585) and 3'UTR A/G (rs11559013). We analyzed the genotypes of 1033 individuals with breast cancer, and 1116 controls; odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression. The effects and functions of polymorphisms were examined using luciferase gene expression assays and real-time PCR analyses. Our data demonstrated that individuals with the rs6437585 CT + TT genotype had an OR of 1.38 (95% CI, 1.11-1.72) for developing breast cancer, compared to those with the CC genotype. The T allele increased the risk of breast cancer in a dose-dependent manner (P (trend) < 0.001). However, there were no significant differences found between cases and controls at the rs11559013 A/G site. Additional experiments that we performed, which focused on reporter gene expression driven by CD166/ALCAM promoters, demonstrated that the presence of an rs6437585 T allele led to greater transcriptional activity than the rs6437585 C allele. This was consistent with the increased cancer risk that we observed in our case-control analysis.
活化白细胞细胞黏附分子（ALCAM，也称为 CD166、MEMD）是细胞表面免疫球蛋白，被认为是乳腺癌的预后标志物。由于 CD166/ALCAM 与肿瘤进展和乳腺癌的转移扩散有显著关联，因此受到越来越多的关注。在 CD166/ALCAM 基因中已经鉴定出两种多态性：5'UTR C/T（rs6437585）和 3'UTR A/G（rs11559013）。我们分析了 1033 名乳腺癌患者和 1116 名对照者的基因型，使用逻辑回归估计比值比（OR）和 95%置信区间（CI）。使用荧光素酶基因表达测定和实时 PCR 分析检查多态性的影响和功能。我们的数据表明，与 CC 基因型相比，rs6437585 CT+TT 基因型的个体发生乳腺癌的 OR 为 1.38（95%CI，1.11-1.72）。T 等位基因以剂量依赖的方式增加乳腺癌的风险（P（趋势）<0.001）。然而，在 rs11559013 A/G 位点，病例与对照之间没有发现显著差异。我们进行的其他实验集中在由 CD166/ALCAM 启动子驱动的报告基因表达上，结果表明，存在 rs6437585 T 等位基因导致转录活性大于 rs6437585 C 等位基因。这与我们在病例对照分析中观察到的增加的癌症风险一致。
