Sims A H, Finnon P, Miller C J, Bouffler S D, Howell A, Scott D, Clarke R B
Breast Biology Group, Paterson Institute for Cancer Research, University of Manchester, UK.
Int J Radiat Biol. 2007 Jun;83(6):409-20. doi: 10.1080/09553000701317366.
To evaluate a transcriptomic approach to identify healthy women at increased risk of breast cancer due to G2-radiosensitivity and look at transcripts that are differentially expressed between individuals.
We perform the first study to assess the association of G2 radiosensitivity with basal gene expression in cultured T-lymphocytes from 11 women with breast cancer and 12 healthy female relatives using Affymetrix GeneChips.
Transcripts associated with radiosensitivity and breast cancer risk were predominantly involved in innate immunity and inflammation, such as interleukins and chemokines. Genes differentially expressed in radiosensitive individuals were more similarly expressed in close family members than in un-related individuals, suggesting heritability of the trait. The expression of tumour protein D52 (TPD52), a gene implicated in cell proliferation, apoptosis, and vesicle trafficking was the most strongly correlated with G2 score while nuclear factor (kappa)-B (NFKB1) was highly inversely correlated with G2 score. NFKB1 is known to be activated by irradiation and its inhibition has been previously shown to increase radiosensitivity.
Gene expression analysis of lymphocytes may provide a quantitative measure of radiation response potential and is a promising marker of breast cancer susceptibility.
评估一种转录组学方法，以识别因G2辐射敏感性而患乳腺癌风险增加的健康女性，并研究个体间差异表达的转录本。
我们进行了第一项研究，使用Affymetrix基因芯片评估11名乳腺癌女性和12名健康女性亲属培养的T淋巴细胞中G2辐射敏感性与基础基因表达的关联。
与辐射敏感性和乳腺癌风险相关的转录本主要涉及先天免疫和炎症，如白细胞介素和趋化因子。在辐射敏感个体中差异表达的基因在近亲家庭成员中比在无亲缘关系的个体中表达更相似，表明该性状具有遗传性。肿瘤蛋白D52（TPD52）的表达与G2评分相关性最强，TPD52是一种与细胞增殖、凋亡和囊泡运输有关的基因，而核因子κB（NFKB1）与G2评分高度负相关。已知NFKB1可被辐射激活，先前已表明抑制它可增加辐射敏感性。
淋巴细胞的基因表达分析可能提供辐射反应潜能的定量测量，是乳腺癌易感性的一个有前景的标志物。
