{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T15:50:39Z","timestamp":1783612239606,"version":"3.55.0"},"reference-count":40,"publisher":"BMJ","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2013,5,22]]},"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Peripheral neuropathy is the dose limiting toxicity of paclitaxel, a chemotherapeutic drug widely used to treat solid tumours. This toxicity exhibits great inter-individual variability of unknown origin. The present study aimed to identify genetic variants associated with paclitaxel induced neuropathy via a whole genome approach.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A genome-wide association study (GWAS) was performed in 144 white European patients uniformly treated with paclitaxel\/carboplatin and for whom detailed data on neuropathy was available. Per allele single nucleotide polymorphism (SNP) associations were assessed by Cox regression, modelling the cumulative dose of paclitaxel up to the development of grade 2 sensory neuropathy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The strongest evidence of association was observed for the ephrin type A receptor 4 (<jats:italic>EPHA4<\/jats:italic>) locus (rs17348202, p=1.0\u00d710<jats:sup>\u20136<\/jats:sup>), and <jats:italic>EPHA6<\/jats:italic> and <jats:italic>EPHA5<\/jats:italic> were among the top 25 and 50 hits (rs301927, p=3.4\u00d710<jats:sup>\u20135<\/jats:sup> and rs1159057, p=6.8\u00d710<jats:sup>\u20135<\/jats:sup>), respectively. A meta-analysis of <jats:italic>EPHA5<\/jats:italic>-rs7349683, the top marker for paclitaxel induced neuropathy in a previous GWAS (r<jats:sup>2<\/jats:sup>=0.79 with rs1159057), gave a hazard ratio (HR) estimate of 1.68 (p=1.4\u00d710<jats:sup>\u22129<\/jats:sup>). Meta-analysis of the second hit of this GWAS, <jats:italic>XKR4<\/jats:italic>-rs4737264, gave a HR of 1.71 (p=3.1\u00d710<jats:sup>\u22128<\/jats:sup>). Imputed SNPs at <jats:italic>LIMK2<\/jats:italic> locus were also strongly associated with this toxicity (HR=2.78, p=2.0\u00d710<jats:sup>\u22127<\/jats:sup>).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study provides independent support of <jats:italic>EPHA5<\/jats:italic>-rs7349683 and <jats:italic>XKR4<\/jats:italic>-rs4737264 as the first markers of risk of paclitaxel induced neuropathy. In addition, it suggests that other <jats:italic>EPHA<\/jats:italic> genes also involved in axonal guidance and repair following neural injury, as well as <jats:italic>LIMK2<\/jats:italic> locus, may play an important role in the development of this toxicity. The identified SNPs could form the basis for individualised paclitaxel chemotherapy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmedgenet-2012-101466","type":"journal-article","created":{"date-parts":[[2013,6,17]],"date-time":"2013-06-17T23:05:28Z","timestamp":1371510328000},"page":"599-605","source":"Crossref","is-referenced-by-count":74,"title":["Genome-wide association study identifies ephrin type A receptors implicated in paclitaxel induced peripheral sensory neuropathy"],"prefix":"10.1136","volume":"50","author":[{"given":"Luis J","family":"Leandro-Garc\u00eda","sequence":"first","affiliation":[{"name":"Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Inglada-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer 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