Radiat Oncol J.  2020 Dec;38(4):226-235. 10.3857/roj.2020.00556.

Harnessing genome-wide association studies to minimize adverse radiation-induced side effects

Affiliations
  • 1Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, CA, USA

Abstract

Radiotherapy is used as definitive treatment in approximately two-thirds of all cancers. However, like any treatment, radiation has significant acute and long-term side effects including secondary malignancies. Even when similar radiation parameters are used, 5%–10% of patients will experience adverse radiation side effects. Genomic susceptibility is thought to be responsible for approximately 40% of the clinical variability observed. In the era of precision medicine, the link between genetic susceptibility and radiation-induced side effects is further strengthening. Genome-wide association studies (GWAS) have begun to identify single-nucleotide polymorphisms (SNPs) attributed to overall and tissue-specific toxicity following radiation for treatment of breast cancer, prostate cancer, and other cancers. Here, we review the use of GWAS in identifying polymorphisms that are predictive of acute and long-term radiation-induced side effects with a focus on chest, pelvic, and head-and-neck irradiation. Integration of GWAS studies with “omic” data, patient characteristics, and clinical correlates into predictive models could decrease radiation-induced side effects while increasing therapeutic efficacy.

Keyword

Radiogenomics; Radiation-induced side effects; Genome-wide association study (GWAS); Normal tissue toxicity; Radiotherapy
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