[an error occurred while processing this directive]|[an error occurred while processing this directive]
放射基因组学与放疗不良反应预测的研究现状
刘俪玭，毕楠，王绿化
100021 北京,国家癌症中心/中国医学科学院北京协和医学院肿瘤医院放疗科
Current status of research on prediction of radiotherapy induced adverse reactions by radiation genomics
Liu Lipin,Bi Nan,Wang Lyuhua
Department of Radiation Oncology,National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences,Peking Union Medical College,Beijing 100021,China
Abstract： The occurrence and severity of radiotherapy-induced adverse events cannot be accounted for or predicted by therapeutic and clinical factors alone. Evidence suggests that genetic variants are associated with adverse effects following radiotherapy. Radiation genomics is the study of genetic variants associated with radiotherapy toxicity. Radiation genomics aims to develop a risk prediction model and uncover the biological mechanisms responsible for radiotherapy toxicity. With the advances in genomics and bioinformatics in the past two decades, radiation genomics has evolved from candidate gene studies to genome-wide association studies, with a series of progress. In this review, we will discuss the study background, design, approaches, challenges, and future directions for radiation genomics.
Liu Lipin,Bi Nan,Wang Lyuhua. Current status of research on prediction of radiotherapy induced adverse reactions by radiation genomics[J]. Chinese Journal of Radiation Oncology, 2017, 26(6): 711-714.
[1] Delaney G,Jacob S,Featherstone C,et al. The role of radiotherapy in cancer treatment:estimating optimal utilization from a review of evidence-based clinical guidelines[J].Cancer,2005,104(6):1129-1137.DOI:10.1002/cncr.21324(2005). [2] Bentzen SM,Constine LS,Deasy JO,et al. Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC):an introduction to the scientific issues[J].Int J Radiat Oncol Biol Phys,2010,76(3 Suppl):S3-9.DOI:10.1016/j.ijrobp.2009.09.040. [3] Barnett GC,West CM,Dunning AM,et al. Normal tissue reactions to radiotherapy:towards tailoring treatment dose by genotype[J].Nat Rev Cancer,2009,9(2):134-142.DOI:10.1038/nrc2587. [4] Kerns SL,Ostrer H,Rosenstein BS.Radiogenomics:using genetics to identify cancer patients at risk for development of adverse effects following radiotherapy[J].Cancer Discov.2014,4(2):155-65.DOI:10.1158/2159-8290.CD-13-0197. [5] Pollard JM,Gatti RA.Clinical radiation sensitivity with DNA repair disorders:an overview[J].Int J Radiat Oncol Biol Phys,2009,74(5):1323-1331.DOI:10.1016/j.ijrobp.2009.02.057. [6] Andreassen CN,Alsner J,Overgaard J.Does variability in normal tissue reactions after radiotherapy have a genetic basis—where and how to look for it[J]? Radiother Oncol,2002,64(2):131-140. [7] Guo Z,Shu Y,Zhou H,et al. Radiogenomics helps to achieve personalized therapy by evaluating patient responses to radiation treatment[J].Carcinogenesis,2015,36(3):307-317.DOI:10.1093/carcin/bgv007. [8] Gabriel SB,Schaffner SF,Nguyen H,et al. The structure of haplotype blocks in the human genome[J].Science,2002,296(5576):2225-2229.DOI:10.1126/science.1069424. [9] Fachal L,Gomez-Caamano A,Barnett GC,et al. A three-stage genome-wide association study identifies a susceptibility locus for late radiotherapy toxicity at 2q24.1[J].Nat Genet,2014,46(8):891-894.DOI:10.1038/ng.3020. [10] Kerns SL,Stock R,Stone N,et al. A 2-stage genome-wide association study to identify single nucleotide polymorphisms associated with development of erectile dysfunction following radiation therapy for prostate cancer[J].Int J Radiat Oncol Biol Phys,2013,85(1):e21-28. DOI:10.1016/j.ijrobp.2012.08.003 [11] Palma DA,Senan S,Tsujino K,et al. Predicting radiation pneumonitis after chemoradiation therapy for lung cancer:an international individual patient data meta-analysis[J].Int J Radiat Oncol Biol Phys,2013,85(2):444-450.DOI:10.1016/j.ijrobp.2012.04.043. [12] Barnett GC,Coles CE,Elliott RM,et al. Independent validation of genes and polymorphisms reported to be associated with radiation toxicity:a prospective analysis study[J].Lancet Oncol,2012,13(1):65-77.DOI:10.1016/s1470-2045(11)70302-3. [13] Barnett GC,Elliott RM,Alsner J,et al. Individual patient data meta-analysis shows no association between the SNP rs1800469 in TGFB and late radiotherapy toxicity[J].Radiother Oncol,2012,105(3):289-295.DOI:10.1016/j.radonc.2012.10.017. [14] Lopez-Guerra JL,Wei Q,Yuan X,et al. Functional promoter rs2868371 variant of HSPB1 associates with radiation-induced esophageal toxicity in patients with non-small-cell lung cancer treated with radio (chemo) therapy[J].Radiother Oncol,2011,101(2):271-277.DOI:10.1016/j.radonc.2011.08.039. [15] Pang Q,Wei Q,Xu T,et al. Functional promoter variant rs2868371 of HSPB1 is associated with risk of radiation pneumonitis after chemoradiation for non-small cell lung cancer[J].Int J Radiat Oncol Biol Phys,2013,85(5):1332-1339.DOI:10.1016/j.ijrobp.2012.10.011. [16] Guerra JL,Gomez D,Wei Q,et al. Association between single nucleotide polymorphisms of the transforming growth factor beta1 gene and the risk of severe radiation esophagitis in patients with lung cancer[J].Radiother Oncol,2012,105(3):299-304.DOI:10.1016/j.radonc.2012.08.014. [17] Talbot CJ,Tanteles GA,Barnett GC,et al. A replicated association between polymorphisms near TNFalpha and risk for adverse reactions to radiotherapy[J].Br J Cancer,2012,107(4):748-753.DOI:10.1038/bjc.2012.290. [18] Edvardsen H,Landmark-Hoyvik H,Reinertsen KV,et al. SNP in TXNRD2 associated with radiation-induced fibrosis:a study of genetic variation in reactive oxygen species metabolism and signaling[J].Int J Radiat Oncol Biol Phys,2013,86(4):791-799.DOI:10.1016/j.ijrobp.2013.02.025. [19] Sachidanandam R,Weissman D,Schmidt SC,et al. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms[J].Nature,2001,409(6822):928-933.DOI:10.1038/35057149. [20] Kerns SL,Ostrer H,Stock R,et al. Genome-wide association study to identify single nucleotide polymorphisms (SNPs) associated with the development of erectile dysfunction in African-American men after radiotherapy for prostate cancer[J].Int J Radiat Oncol Biol Phys,2010,78(5):1292-1300.DOI:10.1016/j.ijrobp.2010.07.036. [21] Kerns SL,Stock RG,Stone NN,et al. A 2-stage genome-wide association study to identify single nucleotide polymorphisms associated with development of erectile dysfunction following radiation therapy for prostate cancer[J].Int J Radiat Oncol Biol Phys,2013,85(1):e21-28.DOI:10.1016/j.ijrobp.2012.08.003. [22] Kerns SL,Stock RG,Stone NN,et al. Genome-wide association study identifies a region on chromosome 11q14.3 associated with late rectal bleeding following radiation therapy for prostate cancer[J].Radiother Oncol,2013,107(3):372-376.DOI:10.1016/j.radonc.2013.05.001. [23] Barnett GC,Thompson D,Fachal L,et al. A genome wide association study (GWAS) providing evidence of an association between common genetic variants and late radiotherapy toxicity[J].Radiother Oncol,2014,111(2):178-185.DOI:10.1016/j.radonc.2014.02.012. [24] Fachal L,Gomez-Caamano A,Barnett GC.A three-stage genome-wide association study identifies a susceptibility locus for late radiotherapy toxicity at 2q24.1[J].Nat Genet,2014,46(8):891-894.DOI:10.1038/ng.3020. [25] Manolio TA,Collins FS,CoxNJ,et al. Finding the missing heritability of complex diseases[J].Nature,2009,461(7265):747-753.DOI:10.1038/nature08494. [26] McClellan J,King MC.Genetic heterogeneity in human disease[J].Cell,2010,141(2):210-217.DOI:10.1016/j.cell.2010.03.032. [27] Dickson SP,Wang K,Krantz I,et al. Rare variants create synthetic genome-wide associations[J].PLoS Biol,2010,8(1):e1000294.DOI:10.1371/journal.pbio.1000294. [28] Salomon MP,Li WL,Edlund CK,et al. GWASeq:targeted re-sequencing follow up to GWAS[J].BMC Genomics,2016,17(1):176.DOI:10.1186/s12864-016-2459-y. [29] Conrad DF,Pinto D,Redon R,et al. Origins and functional impact of copy number variation in the human genome[J].Nature,2010,464(7289):704-712.DOI:10.1038/nature08516. [30] An integrated encyclopedia of DNA elements in the human genome[J].Nature,2012,489(7414):57-74.DOI:10.1038/nature11247. [31] Wang L,Bi N.TGF-beta1 gene polymorphisms for anticipating radiation-induced pneumonitis in non-small-cell lung cancer:different ethnic association[J].J Clin Oncol,2010,28(30):e621-622.DOI:10.1200/jco.2010.31.0458. [32] Myles S,Davison D,Barrett J,et al. Worldwide population differentiation at disease-associated SNPs[J].BMC Med Genomics,2008,1:22.DOI:10.1186/1755-8794-1-22. [33] Zheng G,Freidlin B,Gastwirth JL.Robust genomic control for association studies[J].Am J Hum Genet.2006,78(2):350-356.DOI:10.1086/500054. [34] Falush D,Stephens M,Pritchard JK.Inference of population structure using multilocus genotype data:linked loci and correlated allele frequencies[J].Genetics,2003,164(4):1567-1587. [35] Price AL,Patterson NJ,Plenge RM,et al. Principal components analysis corrects for stratification in genome-wide association studies[J].Nat Genet,2006,38(8):904-909.DOI:10.1038/ng1847. [36] Kerns SL,de Ruysscher D,Andreassen CN,et al. STROGAR-STrengthening the reporting of genetic association studies in radiogenomics[J].Radiother Oncol,2014,110(1):182-188.DOI:10.1016/j.radonc.2013.07.011.
2017, Vol. 26 
