{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hertz DL"],"funding":["NCRR NIH HHS","NCI NIH HHS","NIGMS NIH HHS"],"pagination":["1472-8"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3660078"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["24(6)"],"pubmed_abstract":["BACKGROUND:Paclitaxel-induced neuropathy is an adverse event that often leads to therapeutic disruption and patient discomfort. We attempted to replicate a previously reported association between increased neuropathy risk and CYP2C8*3 genotype. PATIENTS AND METHODS:Demographic, treatment, and toxicity data were collected for paclitaxel-treated breast cancer patients who were genotyped for the CYP2C8*3 K399R (rs10509681) variant. A log-rank test was used in the primary analysis of European-American patients. An additional independent replication was then attempted in a cohort of African-American patients, followed by modeling of the entire patient cohort with relevant covariates. RESULTS:In the primary analysis of 209 European patients, there was an increased risk of paclitaxel-induced neuropathy related to CYP2C8*3 status [HR (per allele) = 1.93 (95% CI: 1.05-3.55), overall log-rank P = 0.006]. The association was replicated in direction and magnitude of effect in 107 African-American patients (P = 0.043). In the Cox model using the entire mixed-race cohort (n = 411), each CYP2C8*3 allele approximately doubled the patient's risk of grade 2+ neuropathy (P = 0.004), and non-Europeans were at higher neuropathy risk than Europeans of similar genotype (P = 0.030). CONCLUSIONS:The increased risk of paclitaxel-induced neuropathy in patients who carry the CYP2C8*3 variant was replicated in two racially distinct patient cohorts."],"journal":["Annals of oncology : official journal of the European Society for Medical Oncology"],"pubmed_title":["CYP2C8*3 increases risk of neuropathy in breast cancer patients treated with paclitaxel."],"pmcid":["PMC3660078"],"funding_grant_id":["P50 CA058223","R01 GM098856","T32GM081057","P30 CA016086","5UL1RR025747-04","5P50CA058223"],"pubmed_authors":["Hertz DL","Drobish A","Motsinger-Reif AA","McLeod HL","Carey LA","Roy S","Dees EC","Clark LS"],"additional_accession":[]},"is_claimable":false,"name":"CYP2C8*3 increases risk of neuropathy in breast cancer patients treated with paclitaxel.","description":"BACKGROUND:Paclitaxel-induced neuropathy is an adverse event that often leads to therapeutic disruption and patient discomfort. We attempted to replicate a previously reported association between increased neuropathy risk and CYP2C8*3 genotype. PATIENTS AND METHODS:Demographic, treatment, and toxicity data were collected for paclitaxel-treated breast cancer patients who were genotyped for the CYP2C8*3 K399R (rs10509681) variant. A log-rank test was used in the primary analysis of European-American patients. An additional independent replication was then attempted in a cohort of African-American patients, followed by modeling of the entire patient cohort with relevant covariates. RESULTS:In the primary analysis of 209 European patients, there was an increased risk of paclitaxel-induced neuropathy related to CYP2C8*3 status [HR (per allele) = 1.93 (95% CI: 1.05-3.55), overall log-rank P = 0.006]. The association was replicated in direction and magnitude of effect in 107 African-American patients (P = 0.043). In the Cox model using the entire mixed-race cohort (n = 411), each CYP2C8*3 allele approximately doubled the patient's risk of grade 2+ neuropathy (P = 0.004), and non-Europeans were at higher neuropathy risk than Europeans of similar genotype (P = 0.030). CONCLUSIONS:The increased risk of paclitaxel-induced neuropathy in patients who carry the CYP2C8*3 variant was replicated in two racially distinct patient cohorts.","dates":{"release":"2013-01-01T00:00:00Z","publication":"2013 Jun","modification":"2021-02-19T18:29:43Z","creation":"2019-03-27T01:10:13Z"},"accession":"S-EPMC3660078","cross_references":{"pubmed":["23413280"],"doi":["10.1093/annonc/mdt018"]}}