The Relationship between Common Genetic Markers of Breast Cancer Risk and Chemotherapy-Induced Toxicity: A Case-Control Study
| Autor: | Dorling, L, Kar, Siddhartha, Michailidou, Kyriaki, Hiller, Louise, Vallier, Anne-Laure, Ingle, Susan, Hardy, Richard, Bowden, Sarah J., Dunn, Janet A., Twelves, Chris, Poole, Christopher J., Caldas, Carlos, Earl, Helena M., Pharoah, Paul D. P., Abraham, Jean E. |
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| Přispěvatelé: | Dorling, Leila [0000-0003-1214-8080], Apollo - University of Cambridge Repository |
| Rok vydání: | 2016 |
| Předmět: |
Cancer Treatment
lcsh:Medicine Toxicology Pathology and Laboratory Medicine White Blood Cells Risk Factors Animal Cells Antineoplastic Combined Chemotherapy Protocols Breast Tumors Medicine and Health Sciences lcsh:Science Pharmaceutics Genomics Middle Aged Survival Rate Oncology Neurology Female Cellular Types Research Article Adult Clinical Oncology Neutropenia Immune Cells Immunology Breast Neoplasms Polymorphism Single Nucleotide Disease-Free Survival RC0254 Drug Therapy Breast Cancer Biomarkers Tumor Genetics Genome-Wide Association Studies Humans Chemotherapy Aged Blood Cells Toxicity lcsh:R Cancers and Neoplasms Biology and Life Sciences Computational Biology Human Genetics Cell Biology Genome Analysis Pharmacogenomic Testing Neuropathy lcsh:Q Clinical Medicine |
| Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 7, p e0158984 (2016) |
| ISSN: | 1932-6203 |
| Popis: | Ninety-four common genetic variants are confirmed to be associated with breast cancer. This study tested the hypothesis that breast cancer susceptibility variants may also be associated with chemotherapy-induced toxicity through shared mechanistic pathways such as DNA damage response, an association that, to our knowledge, has not been previously investigated. The study included breast cancer patients who received neoadjuvant/adjuvant chemotherapy from the Pharmacogenetic SNPs (PGSNPS) study. For each patient, a breast cancer polygenic risk score was created from the 94 breast cancer risk variants, all of which were genotyped or successfully imputed in PGSNPS. Logistic regression was performed to test the association with two clinically important toxicities: taxane- related neuropathy (n = 1279) and chemotherapy-induced neutropenia (n = 1676). This study was well powered (≥96%) to detect associations between polygenic risk score and chemotherapy toxicity. Patients with high breast cancer risk scores experienced less neutropenia compared to those with low risk scores (adjusted p-value = 0.06). Exploratory functional pathway analysis was performed and no functional pathways driving this trend were identified. Polygenic risk was not associated with taxane neuropathy (adjusted p-value = 0.48). These results suggest that breast cancer patients with high genetic risk of breast cancer, conferred by common variants, can safely receive standard chemotherapy without increased risk of taxane-related sensory neuropathy or chemotherapy-induced neutropenia and may experience less neutropenia. As neutropenia has previously been associated with improved survival and may reflect drug efficacy, these patients may be less likely to benefit from standard chemotherapy treatment.\ud \ud |
| Databáze: | OpenAIRE |
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