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The relationship between common genetic markers of breast cancer risk and chemotherapy-induced toxicity : a case-control study
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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. and Abraham, Jean E. (2016) The relationship between common genetic markers of breast cancer risk and chemotherapy-induced toxicity : a case-control study. PLoS One, 11 (7). e0158984. doi:10.1371/journal.pone.0158984 ISSN 1932-6203.
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Official URL: http://dx.doi.org/10.1371/journal.pone.0158984
Abstract
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.
Item Type: | Journal Article | ||||||
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Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) | ||||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Clinical Trials Unit Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Breast -- Cancer -- Risk factors , Genetic disorders -- Statistics, Tumors, Chemotherapy | ||||||
Journal or Publication Title: | PLoS One | ||||||
Publisher: | Public Library of Science | ||||||
ISSN: | 1932-6203 | ||||||
Official Date: | 8 July 2016 | ||||||
Dates: |
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Volume: | 11 | ||||||
Number: | 7 | ||||||
Article Number: | e0158984 | ||||||
DOI: | 10.1371/journal.pone.0158984 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||
Date of first compliant deposit: | 10 August 2016 | ||||||
Date of first compliant Open Access: | 11 August 2016 | ||||||
Funder: | Cancer Research UK (CRUK), National Institute for Health Research (Great Britain) (NIHR) | ||||||
Grant number: | C507/A6306 (CRUK), C10097/A7484 (CRUK), C57/A4180 (CRUK) |
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