دورية أكاديمية
Patients with a High Polygenic Risk of Breast Cancer do not have An Increased Risk of Radiotherapy Toxicity.
| العنوان: | Patients with a High Polygenic Risk of Breast Cancer do not have An Increased Risk of Radiotherapy Toxicity. |
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| المؤلفون: | Dorling, Leila, Barnett, Gillian C, Michailidou, Kyriaki, Coles, Charlotte E, Burnet, Neil G, Yarnold, John, Elliott, Rebecca M, Dunning, Alison M, Pharoah, Paul DP, West, Catharine M |
| بيانات النشر: | American Association for Cancer Research (AACR) //dx.doi.org/10.1158/1078-0432.ccr-15-1080 Clin Cancer Res |
| سنة النشر: | 2016 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | Alleles, Breast Neoplasms, Cohort Studies, Combined Modality Therapy, Female, Genetic Predisposition to Disease, Genotype, Humans, Odds Ratio, Polymorphism, Single Nucleotide, Radiation Tolerance, Risk, Tumor Burden |
| الوصف: | PURPOSE: It has been hypothesized that increased predisposition to breast cancer may correlate with radiosensitivity, and thus increased risk of toxicity following breast irradiation. This study investigated the relationship between common breast cancer risk variants and radiotherapy toxicity. EXPERIMENTAL DESIGN: SNP genotypes were determined in female breast cancer patients from the RAPPER (Radiogenomics: Assessment of polymorphisms for predicting the effects of radiotherapy) study using the Illumina CytoSNP12 genome-wide array. A further 15,582,449 genotypes were imputed using the 1000 Genomes Project reference panel. Patient (n = 1,160) polygenic risk scores were generated by summing risk-allele dosages, both unweighted and weighted by published effect sizes for breast cancer risk. Regression models were used to test associations of individual variants and polygenic risk scores with acute and late toxicity phenotypes (telangiectasia, breast edema, photographically assessed shrinkage, induration, pigmentation, breast pain, breast sensitivity, and overall toxicity). RESULTS: Genotypes of 90 confirmed breast cancer risk variants were accurately determined and polygenic risk scores were approximately normally distributed. Variant rs6964587 was associated with increased breast edema 5 years following radiotherapy (Beta, 0.22; 95% confidence interval, 0.09-0.34; P = 7 × 10(-4)). No other associations were found between individual variants or the unweighted (P > 0.17) or weighted (P > 0.13) polygenic risk score and radiotherapy toxicity. This study had >87% power to detect an association between the polygenic risk score (relative risk > 1.1) and toxicity. CONCLUSIONS: Cancer patients with a high polygenic predisposition to breast cancer do not have an increased risk of radiotherapy toxicity up to 5 years following radiotherapy but individual variants may increase risk. ; NP is Cancer Research UK Clinician Scientist Fellow. The COGS project was funded through a European Commission's Seventh Framework ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/252588Test |
| الإتاحة: | https://www.repository.cam.ac.uk/handle/1810/252588Test |
| رقم الانضمام: | edsbas.B245EDE6 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |