萊斯特大學(xué)的醫(yī)學(xué)研究人員宣布了一項(xiàng)很有潛力的“特殊”乳腺癌研究進(jìn)展,。他們確定出兩個(gè)與癌癥治療效果差有關(guān)的基因,。
這項(xiàng)研究成果是在世界上首次確定出潛力預(yù)測(cè)哪些乳腺癌患者對(duì)放射治療效果差標(biāo)志基因,。
這項(xiàng)研究由Drs Paul Symonds以及Mark Plumb等人完成，研究成果發(fā)表在British Journal of Cancer期刊,。
Dr Symonds指出，放射線治療是乳腺癌治療很重要的一環(huán),，但卻有少部份的人會(huì)發(fā)生很嚴(yán)重的副作用,。在進(jìn)行放射線治療時(shí),，病人的皮膚會(huì)發(fā)紅或脫皮，乳房會(huì)皺縮,，皮膚底下的組織會(huì)變硬,、變厚或纖維化。研究人員在詳細(xì)研究這些病人后,，發(fā)現(xiàn)有兩個(gè)基因與上述征狀有明顯的關(guān)聯(lián),。
研究發(fā)現(xiàn),，大約有8%的婦女?dāng)y帶纖維癥基因(fibrosis gene),，而有長(zhǎng)期慢性疼痛的人中,，其組織纖維化的風(fēng)險(xiǎn)要比一般人高出15倍，而被鑒定出來(lái)的這兩個(gè)基因就是乳腺癌疼痛的標(biāo)記基因,，預(yù)測(cè)準(zhǔn)確率達(dá)到50—60%,。
研究人員指出,，如果還能再找出造成皮膚發(fā)紅或脫皮的基因,，那么就能將預(yù)測(cè)準(zhǔn)確率提高到100%,。將來(lái),，也許能通過(guò)這些指針基因來(lái)預(yù)測(cè)那些人對(duì)放射線治療是否適合。
原始出處:
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: [email protected]
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
