Individual patient data meta-analysis shows a significant association between the ATM rs1801516 SNP and toxicity after radiotherapy in 5456 breast and prostate cancer patients

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• 作者：Christian Nicolaj Andreassen^a ; ^{nicolaj@oncology.au.dk} ; Barry S. Rosenstein^b ; Sarah L. Kerns^c ; ^b ; Harry Ostrer^d ; Dirk De Ruysscher^e ; Jamie A. Cesaretti^f ; Gillian C. Barnett^g ; ^h ; Alison M. Dunning^g ; ^h ; Leila Dorling^h ; Catharine M.L. Westⁱ ; Neil G. Burnet^g ; Rebecca Elliott^g ; Charlotte Coles^g ; Emma Hall^j ; Laura Fachal^k ; Ana Vega^k ; Antonio Gó ; mez-Caamañ ; o^l ; Christopher J. Talbot^m ; R. Paul Symondsⁿ ; Kim De Ruyck^o ; Hubert Thierens^o ; Piet Ost^p ; Jenny Chang-Claude^q ; ^r ; Petra Seibold^q ; Odilia Popanda^s ; Marie Overgaard^a ; David Dearnaley^t ; Matthew R. Sydes^u ; David Azria^v ; Christine Anne Koch^w ; Matthew Parliament^x ; Michael Blackshaw^x ; Michael Sia^y ; Maria J. Fuentes-Raspall^z ; Teresa Ramon y Cajal^aa ; Agustin Barnadas^aa ; Danny Vesprini^ab ; Sara Gutié ; rrez-Enrí ; quez^ac ; Meritxell Mollà ; ^ad ; Orland Dí ; ez^ae ; John R. Yarnold^t ; Jens Overgaard^a ; Sø ; ren M. Bentzen^af ; Jan Alsner^a ; On behalf of the International Radiogenomics Consortium (RgC)
• 关键词：Normal tissue toxicity ; Radiosensitivity ; Ataxia telangiectasia mutated ; p.Asp1853Asn ; c.5557G> ; A
• 刊名：Radiotherapy and Oncology
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：121
• 期：3
• 页码：431-439
• 全文大小：547 K
• 卷排序：121

文摘

Several small studies have indicated that the ATM rs1801516 SNP is associated with risk of normal tissue toxicity after radiotherapy. However, the findings have not been consistent. In order to test this SNP in a well-powered study, an individual patient data meta-analysis was carried out by the International Radiogenomics Consortium.Materials and methodsThe analysis included 5456 patients from 17 different cohorts. 2759 patients were given radiotherapy for breast cancer and 2697 for prostate cancer. Eight toxicity scores (overall toxicity, acute toxicity, late toxicity, acute skin toxicity, acute rectal toxicity, telangiectasia, fibrosis and late rectal toxicity) were analyzed. Adjustments were made for treatment and patient related factors with potential impact on the risk of toxicity.ResultsFor all endpoints except late rectal toxicity, a significantly increased risk of toxicity was found for carriers of the minor (Asn) allele with odds ratios of approximately 1.5 for acute toxicity and 1.2 for late toxicity. The results were consistent with a co-dominant pattern of inheritance.ConclusionThis study convincingly showed a significant association between the ATM rs1801516 Asn allele and increased risk of radiation-induced normal tissue toxicity.