莱斯特大学的医学研究人员宣布了一项很有潜力的“特殊”乳腺癌研究进展。他们确定出两个与癌症治疗效果差有关的基因。
这项研究成果是在世界上首次确定出潜力预测哪些乳腺癌患者对放射治疗效果差标志基因。
这项研究由Drs Paul Symonds以及Mark Plumb等人完成，研究成果发表在British Journal of Cancer期刊。
Dr Symonds指出，放射线治疗是乳腺癌治疗很重要的一环，但却有少部份的人会发生很严重的副作用。在进行放射线治疗时，病人的皮肤会发红或脱皮，乳房会皱缩，皮肤底下的组织会变硬、变厚或纤维化。研究人员在详细研究这些病人后，发现有两个基因与上述征状有明显的关联。
研究发现，大约有8%的妇女携带纤维症基因(fibrosis gene)，而有长期慢性疼痛的人中，其组织纤维化的风险要比一般人高出15倍，而被鉴定出来的这两个基因就是乳腺癌疼痛的标记基因，预测准确率达到50—60%。
研究人员指出，如果还能再找出造成皮肤发红或脱皮的基因，那么就能将预测准确率提高到100%。将来，也许能通过这些指针基因来预测那些人对放射线治疗是否适合。
原始出处:
Genetics and Genomics
British Journal of Cancer (2007) 96, 1001-1007.
doi:10.1038/sj.bjc.6603637 Published online 27 February 2007
The late radiotherapy normal tissue injury phenotypes of telangiectasia, fibrosis and atrophy in breast cancer patients have distinct genotype-dependent causes
G Giotopoulos1, R P Symonds2, K Foweraker2, M Griffin3, I Peat2, A Osman2 and M Plumb1
1Department of Genetics, University of Leicester, Leicester LE1 7RH, UK
2Department of Cancer Studies and Molecular Medicine, University of Leicester, Level 2, Osborne Building, Leicester Royal Infirmary, Leicester LE1 5WW, UK
3Department of Oncology, Nottingham University Hospitals NHS Trust, CITY Hospital Campus, ICT Services, Hucknall Road, Nottingham, UK
Correspondence to: Dr RP Symonds, E-mail: rps8@le.ac.uk
Received 15 November 2006; revised 19 January 2007; accepted 23 January 2007; published online 27 February 2007
Abstract
The relationship between late normal tissue radiation injury phenotypes in 167 breast cancer patients treated with radiotherapy and: (i) radiotherapy dose (boost); (ii) an early acute radiation reaction and (iii) genetic background was examined. Patients were genotyped at single nucleotide polymorphisms (SNPs) in eight candidate genes. An early acute reaction to radiation and/or the inheritance of the transforming growth factor-1 (TGF1 -509T) SNP contributed to the risk of fibrosis. In contrast, an additional 15 Gy electron boost and/or the inheritance of X-ray repair cross-complementing 1 (XRCC1) (R399Q) SNP contributed to the risk of telangiectasia. Although fibrosis, telangiectasia and atrophy, all contribute to late radiation injury, the data suggest that they have distinct underlying genetic and radiobiological causes. Fibrosis risk is associated with an inflammatory response (an acute reaction and/or TGF1), whereas telangiectasia is associated with vascular endothelial cell damage (boost and/or XRCC1). Atrophy is associated with an acute response, but the genetic predisposing factors that determine the risk of an acute response or atrophy have yet to be identified. A combined analysis of two UK breast cancer patient studies shows that 8% of patients are homozygous (TT) for the TGF1 (C-509T) variant allele and have a 15-fold increased risk of fibrosis following radiotherapy (95% confidence interval: 3.76-60.3; P=0.000003) compared with (CC) homozygotes.
Keywords: breast cancer; radiation injury; TGF1; XRCC1; fibrosis; telangiectasia
