Tyck till om SwePub Sök
här!
Search: WFRF:(Garcia Redondo Alberto) >
Targeted sequencing...
Targeted sequencing reveals low-frequency variants in EPHA genes as markers of paclitaxel-induced peripheral neuropathy.
-
- Apellániz-Ruiz, Maria (author)
- Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain
-
- Tejero, Héctor (author)
- Translational Bioinformatics Unit, Spanish National Cancer Research Centre, Madrid, Spain
-
- Inglada-Pérez, Lucía (author)
- Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain. ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain
-
show more...
-
- Sánchez-Barroso, Lara (author)
- Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain
-
- Gutiérrez-Gutiérrez, Gerardo (author)
- Neurology Section, Hospital Universitario Infanta Sofía, Madrid, Spain
-
- Calvo, Isabel (author)
- Medical Oncology Department, Hospital Montepríncipe, Madrid, Spain. Medical Oncology Department, Centro Integral Oncológico Clara Campal, Madrid, Spain
-
- Castelo, Beatriz (author)
- Medical Oncology Department, Hospital Universitario La Paz, Madrid, Spain
-
- Redondo, Andrés (author)
- Medical Oncology Department, Hospital Universitario La Paz, Madrid, Spain
-
- García-Donás, Jesus (author)
- Gynecological and Genitourinary Tumors Programme, Centro Integral Oncológico Clara Campal, Madrid, Spain
-
- Romero-Laorden, Nuria (author)
- Gynecological and Genitourinary Tumors Programme, Centro Integral Oncológico Clara Campal, Madrid, Spain
-
- Sereno, Maria (author)
- Medical Oncology Department, Hospital Universitario Infanta Sofía, Madrid, Spain
-
- Merino, María (author)
- Medical Oncology Department, Hospital Universitario Infanta Sofía, Madrid, Spain
-
- Currás-Freixes, Maria (author)
- Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain
-
- Montero-Conde, Cristina (author)
- Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain
-
- Mancikova, Veronika (author)
- Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain
-
- Åvall-Lundqvist, Elisabeth, 1957- (author)
- Karolinska Institutet,Linköpings universitet,Avdelningen för Kirurgi, Ortopedi och Onkologi,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US
-
- Green, Henrik (author)
- Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten,Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden
-
- Al-Shahrour, Fatima (author)
- Translational Bioinformatics Unit, Spanish National Cancer Research Centre, Madrid, Spain
-
- Cascon, Alberto (author)
- Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain. ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain
-
- Robledo, Mercedes (author)
- Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain.ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain
-
- Rodriguez-Antona, Cristina (author)
- Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain.ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain
-
show less...
-
(creator_code:org_t)
- American Association of Cancer Research, 2017
- 2017
- English.
-
In: Clinical Cancer Research. - : American Association of Cancer Research. - 1078-0432 .- 1557-3265. ; 23:5, s. 1227-1235
- Related links:
-
https://liu.diva-por... (primary) (Raw object)
-
show more...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
http://kipublication...
-
show less...
Abstract
Subject headings
Close
- PURPOSE: Neuropathy is the dose limiting toxicity of paclitaxel and a major cause for decreased quality of life. Genetic factors have been shown to contribute to paclitaxel neuropathy susceptibility; however, the major causes for inter-individual differences remain unexplained. In this study we identified genetic markers associated with paclitaxel-induced neuropathy through massive sequencing of candidate genes.EXPERIMENTAL DESIGN: We sequenced the coding region of 4 EPHA genes, 5 genes involved in paclitaxel pharmacokinetics and 30 Charcot-Marie-Tooth genes, in 228 cancer patients with no/low neuropathy or high grade neuropathy during paclitaxel treatment. An independent validation series included 202 paclitaxel-treated patients. Variation-/ gene-based analyses were used to compare variant frequencies among neuropathy groups and Cox regression models were used to analyze neuropathy evolution along treatment.RESULTS: Gene-based analysis identified EPHA6 as the gene most significantly associated with paclitaxel-induced neuropathy. Low frequency non-synonymous variants in EPHA6 were present exclusively in patients with high neuropathy and all affected the ligand binding domain. Accumulated dose analysis in the discovery series showed a significantly higher neuropathy risk for EPHA5/6/8 low-frequency non-synonymous variant carriers (HR=14.60, 95%CI=2.33-91.62, P=0.0042) and an independent cohort confirmed an increased neuropathy risk (HR=2.07, 95%CI=1.14-3.77, P=0.017). Combining the series gave an estimated 2.50-fold higher risk of neuropathy (95%CI=1.46-4.31; P=9.1x10(-4)).CONCLUSION: This first study sequencing EPHA genes revealed that low frequency variants in EPHA6, EPHA5 and EPHA8 contribute to the susceptibility to paclitaxel-induced neuropathy. Furthermore, EPHAs neuronal injury repair function suggests that these genes might constitute important neuropathy markers for many neurotoxic drugs.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Apellániz-Ruiz, ...
-
Tejero, Héctor
-
Inglada-Pérez, L ...
-
Sánchez-Barroso, ...
-
Gutiérrez-Gutiér ...
-
Calvo, Isabel
-
show more...
-
Castelo, Beatriz
-
Redondo, Andrés
-
García-Donás, Je ...
-
Romero-Laorden, ...
-
Sereno, Maria
-
Merino, María
-
Currás-Freixes, ...
-
Montero-Conde, C ...
-
Mancikova, Veron ...
-
Åvall-Lundqvist, ...
-
Green, Henrik
-
Al-Shahrour, Fat ...
-
Cascon, Alberto
-
Robledo, Mercede ...
-
Rodriguez-Antona ...
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Clinical Medicin ...
- Articles in the publication
-
Clinical Cancer ...
- By the university
-
Linköping University
-
Karolinska Institutet