Chen Taiping, Jackson Chad R, Link Andrew, Markey Michael P, Colligan Bruce M, Douglass Larry E, Pemberton Jackson O, Deddens James A, Graff Jeremy R, Carter Julia H
Wood Hudson Cancer Research Laboratory, 931 Isabella Street, Newport, KY 41071-4701, USA.
Clin Cancer Res. 2006 Jan 15;12(2):392-7. doi: 10.1158/1078-0432.CCR-05-1518.
The transforming growth factor-beta (TGF-beta) signaling pathway has been frequently implicated in breast cancer. An intronic variant (Int7G24A) of TGF-beta receptor type I (TGFBR1) is associated with kidney and bladder cancers in our recent study. We hypothesize that this germline variant may be involved in development and progression of breast cancer.
Case-control studies were designed from archived paraffin-embedded tissue specimens from the same geographic area with a homogenous ethnic population. We analyzed 223 patients (25 with preinvasive tumors and 198 with invasive and metastatic breast cancers) and 153 noncancer controls. The Int7G24A was identified by PCR-RFLP. Another germline deletion (TGFBR1*6A) and somatic mutations in the TGFBR1 were also analyzed by PCR and single-strand conformational polymorphism.
The Int7G24A allele was evident in 32% of patients with preinvasive neoplasms and 48% of patients with invasive breast cancers compared with 26% controls (P = 0.00008). In addition, 11 (5.6%) homozygous Int7G24A carriers were found in patients with invasive breast cancers, whereas only 3 (2%) homozygous carriers were found in the control group. The TGFBR1*6A allele was not significantly associated with breast cancer patients and only one somatic mutation was found in 71 breast cancers.
These data suggest that the germline Int7G24A variant may represent a risk factor for invasive breast cancer and a marker for breast cancer progression. A separate study with a larger sample size is warranted to validate the association of the Int7G24A with human breast cancer.
转化生长因子-β（TGF-β）信号通路常与乳腺癌相关。在我们最近的研究中，I型TGF-β受体（TGFBR1）的一个内含子变异（Int7G24A）与肾癌和膀胱癌有关。我们推测这种种系变异可能参与乳腺癌的发生和发展。
病例对照研究采用来自同一地理区域、种族同质的存档石蜡包埋组织标本进行。我们分析了223例患者（25例为原位肿瘤患者，198例为浸润性和转移性乳腺癌患者）和153例非癌症对照。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）鉴定Int7G24A。还通过PCR和单链构象多态性分析了另一种种系缺失（TGFBR1*6A）和TGFBR1中的体细胞突变。
与26%的对照相比，Int7G24A等位基因在32%的原位肿瘤患者和48%的浸润性乳腺癌患者中明显存在（P = 0.00008）。此外，在浸润性乳腺癌患者中发现11例（5.6%）纯合Int7G24A携带者，而在对照组中仅发现3例（2%）纯合携带者。TGFBR1*6A等位基因与乳腺癌患者无显著相关性，在71例乳腺癌中仅发现1例体细胞突变。
这些数据表明种系Int7G24A变异可能是浸润性乳腺癌的一个危险因素和乳腺癌进展的一个标志物。需要进行一项样本量更大的单独研究来验证Int7G24A与人类乳腺癌的关联。
