Association Between Polymorphisms in DNA Damage Repair Genes and Radiation Therapy–Induced Early Adverse Skin Reactions in a Breast Cancer Population: A Polygenic Risk Score Approach
| Autor: | Susan Slifer, Jennifer J. Hu, Jean L. Wright, Eunkyung Lee, Cristiane Takita, Robert B. Hines, Eden R. Martin, Sung Yong Eum |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Oncology Cancer Research medicine.medical_specialty DNA Repair Population Breast Neoplasms Single-nucleotide polymorphism Polymorphism Single Nucleotide Risk Assessment 030218 nuclear medicine & medical imaging 03 medical and health sciences 0302 clinical medicine Breast cancer Internal medicine Humans Medicine SNP Radiology Nuclear Medicine and imaging Clinical significance Radiation Injuries education Aged Skin Aged 80 and over education.field_of_study Radiation business.industry Middle Aged medicine.disease 030220 oncology & carcinogenesis Cohort ERCC2 Population study Female business |
| Zdroj: | International Journal of Radiation Oncology*Biology*Physics. 106:948-957 |
| ISSN: | 0360-3016 |
| DOI: | 10.1016/j.ijrobp.2019.12.021 |
| Popis: | Purpose Genetic variations in DNA damage repair (DDR) genes may influence radiation therapy (RT)–induced acute normal tissue toxicity in patients with breast cancer. Identifying an individual or multiple single-nucleotide polymorphisms (SNPs) associated with RT–induced early adverse skin reactions (EASR) is critical for precision medicine in radiation oncology. Methods and Materials At the completion of RT, EASR was assessed using the Oncology Nursing Society scale (0-6) in 416 patients with breast cancer, and Oncology Nursing Society score ≥4 was considered RT-induced EASR. PLINK set-based tests and subsequent individual SNP association analyses were conducted to identify genes and SNPs associated with EASR among the 53 DDR genes and 1968 SNPs. A weighted polygenic risk score (PRS) model was constructed to ascertain the association between the joint effect of risk alleles and EASR. Results The study population consisted of 264 Hispanic whites, 86 blacks or African Americans, 55 non-Hispanic whites, and 11 others. A total of 115 patients (27.6%) developed EASR. Five genes (ATM, CHEK1, ERCC2, RAD51C, and TGFB1) were significantly associated with RT-induced EASR. Nine SNPs within these 5 genes were further identified: ATM rs61915066, CHEK1 rs11220184, RAD51C rs302877, rs405684, TBFB1 rs4803455, rs2241714, and ERCC2 rs60152947, rs10404465, rs1799786. In a multivariable-adjusted PRS model, patients in a higher quartile of PRS were more likely to develop EASR compared with patients in the lowest quartile (ORq2 vs.q1 = 1.94, 95% CI, 0.86-4.39; ORq3 vs.q1 = 3.46, 95% CI, 1.57-7.63; ORq4 vs.q1 = 8.64, 95% CI, 3.92-19.02; and Ptrend Conclusions We newly identified the associations between 9 SNPs in ATM, CHEK1, RAD51C, TGFB1, and ERCC2 and RT-induced EASR. PRS modeling showed its potential in identifying populations at risk. Multiple SNPs in DDR genes may jointly contribute to interindividual variation in RT-induced EASR. Validation in an independent external cohort is required to determine the clinical significance of these predictive biomarkers. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|