SNPs in genes implicated in radiation response are associated with radiotoxicity and evoke roles as predictive and prognostic biomarkers

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• 作者：Ghazi Alsbeih (19) (22)
  Medhat El-Sebaie (20)
  Najla Al-Harbi (19)
  Khaled Al-Hadyan (19)
  Mohamed Shoukri (21)
  Nasser Al-Rajhi (20)
  
• 关键词：Single nucleotide polymorphism (SNP) ; Radiosensitivity ; Late reactions to radiotherapy ; Fibrosis ; Follow up ; Nasopharyngeal carcinoma
• 刊名：Radiation Oncology
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：8
• 期：1
• 全文大小：332KB
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• 作者单位：Ghazi Alsbeih (19) (22)
  Medhat El-Sebaie (20)
  Najla Al-Harbi (19)
  Khaled Al-Hadyan (19)
  Mohamed Shoukri (21)
  Nasser Al-Rajhi (20)
  
  19. Radiation Biology Section, Biomedical Physics Department, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh, 11211, Saudi Arabia
  22. Radiation Biology Section, Biomedical Physics Department, KFSHRC, MBC-03, P.O. Box 3354, Riyadh, 11211, Saudi Arabia
  20. Radiation Oncology Section, Oncology Centre, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh, 11211, Saudi Arabia
  21. National Biotechnology Center, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh, 11211, Saudi Arabia
  

文摘

Background Biomarkers are needed to individualize cancer radiation treatment. Therefore, we have investigated the association between various risk factors, including single nucleotide polymorphisms (SNPs) in candidate genes and late complications to radiotherapy in our nasopharyngeal cancer patients. Methods A cohort of 155 patients was included. Normal tissue fibrosis was scored using RTOG/EORTC grading system. A total of 45 SNPs in 11 candidate genes (ATM, XRCC1, XRCC3, XRCC4, XRCC5, PRKDC, LIG4, TP53, HDM2, CDKN1A, TGFB1) were genotyped by direct genomic DNA sequencing. Patients with severe fibrosis (cases, G3-4, n--8) were compared to controls (G0-2, n--07). Results Univariate analysis showed significant association (P-lt;-.05) with radiation complications for 6 SNPs (ATM G/A rs1801516, HDM2 promoter T/G rs2279744 and T/A rs1196333, XRCC1 G/A rs25487, XRCC5 T/C rs1051677 and TGFB1 C/T rs1800469). In addition, Kaplan-Meier analyses have also highlighted significant association between genotypes and length of patients-follow-up after radiotherapy. Multivariate logistic regression has further sustained these results suggesting predictive and prognostic roles of SNPs. Conclusions Univariate and multivariate analysis suggest that radiation toxicity in radiotherapy patients are associated with certain SNPs, in genes including HDM2 promoter studied for the 1st time. These results support the use of SNPs as genetic predictive markers for clinical radiosensitivity and evoke a prognostic role for length of patients-follow-up after radiotherapy.