Zhang Mei, Guo Ling-Ling, Cheng Zhongqin, Liu Reng-Yun, Lu Yufeng, Qian Qian, Lei Zhe, Zhang Hong-Tao
Department of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou 215004.
Oncol Lett. 2011 Jul;2(4):653-658. doi: 10.3892/ol.2011.312. Epub 2011 May 13.
Little is known about the correlation between TGFBR2 G-875A and breast cancer risk. Moreover, the associations of the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) in breast cancer tissues with the TGFB1 C-509T, T+29C and TGFBR2 G-875A polymorphisms remain to be determined. In this study, we genotyped for TGFB1 C-509T, T+29C and TGFBR2 G-875A in fresh surgically resected tissues (n=82) and archived paraffin-embedded specimens (n=88) from 170 patients with breast cancer, as well as peripheral blood samples from 178 cancer-free female individuals. Evaluation of ER, PR and HER2 expression was performed using immunohistochemical staining. Logistic regression analysis was carried out to determine the risk of breast cancer by calculating the odds ratios (ORs) and their 95% confidence intervals (CIs). As a result, no difference was observed in the TGFB1 C-509T, T+29C genotype and allele frequencies between patients and controls. However, the frequency of the TGFBR2 -875A allele was marginally higher in cancer-free female individuals than that of women with breast cancer (24.2 vs. 17.9%, P=0.05). Notably, when stratification was performed by ER, PR and HER2 expression, the TGFBR2 -875A allele was found to correlate significantly to a decreased risk of breast cancer with ER(+) (OR=0.57, 95% CI 0.35-0.92), PR(+) (OR=0.54, 95% CI 0.34-0.88), ER(+)PR(+) (OR=0.55, 95% CI 0.33-0.92) and HER2(-) (OR=0.55, 95% CI 0.34-0.88) under a dominant genetic model. In conclusion, this is the first study to suggest that the TGFBR2 -875A allele modifies predisposition to breast cancer with an expression of ER(+), PR(+), ER(+)PR(+) and HER2(-).
关于转化生长因子β受体2（TGFBR2）基因G-875A与乳腺癌风险之间的相关性，目前所知甚少。此外，乳腺癌组织中雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体2（HER2）的表达与转化生长因子β1（TGFB1）基因C-509T、T+29C以及TGFBR2基因G-875A多态性之间的关联仍有待确定。在本研究中，我们对170例乳腺癌患者手术切除的新鲜组织（n=82）和存档石蜡包埋标本（n=88）以及178名无癌女性个体的外周血样本进行了TGFB1基因C-509T、T+29C和TGFBR2基因G-875A的基因分型。采用免疫组织化学染色法评估ER、PR和HER2的表达。通过计算比值比（OR）及其95%置信区间（CI），进行逻辑回归分析以确定乳腺癌风险。结果显示，患者与对照组之间在TGFB1基因C-509T、T+29C的基因型和等位基因频率上未观察到差异。然而，无癌女性个体中TGFBR2基因-875A等位基因的频率略高于乳腺癌女性患者（24.2%对17.9%，P=0.05）。值得注意的是，当按ER、PR和HER2表达进行分层时，发现在显性遗传模型下，TGFBR2基因-875A等位基因与ER（+）（OR=0.57，95%CI 0.35-0.92）、PR（+）（OR=0.54，95%CI 0.34-0.88）、ER（+）PR（+）（OR=0.55，95%CI 0.33-0.92）和HER2（-）（OR=0.55，95%CI 0.34-0.88）乳腺癌风险降低显著相关。总之，这是第一项表明TGFBR2基因-875A等位基因可改变ER（+）、PR（+）、ER（+）PR（+）和HER2（-）表达的乳腺癌易感性的研究。
