Song B, Margolin S, Skoglund J, Zhou X, Rantala J, Picelli S, Werelius B, Lindblom A
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm 171 76, Sweden.
Br J Cancer. 2007 Oct 22;97(8):1175-9. doi: 10.1038/sj.bjc.6603961. Epub 2007 Sep 11.
Two common variants in transforming growth factor-beta receptor 1 (TGFBR1), TGFBR1()6A and Int7G24A, A allele, have been shown to act as low-penetrance tumour susceptibility alleles in several common cancers, including breast cancer. We evaluated the TGFBR1 9A/6A and Int7G24A variant frequencies in two breast cancer cohorts; a population-based cohort of breast cancer with defined family history (n=459) and in breast cancer patients from a familial cancer clinic (n=340) and in 856 controls from the Stockholm region. The familial patients from both cohorts were further divided into high- and low-risk familial breast cancer based on pedigree analysis. There was no overall association with either variant and breast cancer risk. The TGFBR1()6A allelic frequency was, however, higher in low-risk familial breast cancer (0.138), compared to controls (0.106; P=0.04). No significant difference was found in the high-risk familial (0.102) or sporadic cases (0.109; P=0.83 and 0.83, respectively). TGFBR1()6A carrier status was further associated with a high-grade sporadic breast cancer (odds ratio: 2.27; 95% confidence interval: 1.01-5.11; P=0.049). These results indicate that the TGFBR1()6A variant may be associated with an increased risk of low-risk familial breast cancer and might be a marker for poorly differentiated breast cancer. The Int7G24A variant was not associated with breast cancer risk or clinical presentation of the disease including prognosis in our material.
转化生长因子-β受体1（TGFBR1）中的两个常见变体，即TGFBR1()6A和Int7G24A的A等位基因，已被证明在包括乳腺癌在内的几种常见癌症中作为低外显率肿瘤易感性等位基因起作用。我们评估了两个乳腺癌队列中TGFBR1 9A/6A和Int7G24A变体的频率；一个基于人群的有明确家族史的乳腺癌队列（n = 459）、来自家族性癌症诊所的乳腺癌患者（n = 340）以及来自斯德哥尔摩地区的856名对照。根据系谱分析，两个队列中的家族性患者进一步分为高风险和低风险家族性乳腺癌。这两个变体与乳腺癌风险均无总体关联。然而，与对照组（0.106；P = 0.04）相比，低风险家族性乳腺癌中TGFBR1()6A等位基因频率更高（0.138）。在高风险家族性病例（0.102）或散发性病例（分别为0.109；P = 0.83和0.83）中未发现显著差异。TGFBR1()6A携带者状态还与高级别散发性乳腺癌相关（优势比：2.27；95%置信区间：1.01 - 5.11；P = 0.049）。这些结果表明，TGFBR1()6A变体可能与低风险家族性乳腺癌风险增加相关，并且可能是低分化乳腺癌的一个标志物。在我们的研究材料中，Int7G24A变体与乳腺癌风险或疾病的临床表现（包括预后）无关。
