biostudies-literatureHertz DLNCRR NIH HHSNCI NIH HHSNIGMS NIH HHS1472-8https://www.ebi.ac.uk/biostudies/studies/S-EPMC3660078biostudies-literatureUnknown24(6)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.Annals of oncology : official journal of the European Society for Medical OncologyCYP2C8*3 increases risk of neuropathy in breast cancer patients treated with paclitaxel.PMC3660078P50 CA058223R01 GM098856T32GM081057P30 CA0160865UL1RR025747-045P50CA058223Hertz DLDrobish AMotsinger-Reif AAMcLeod HLCarey LARoy SDees ECClark LSfalseCYP2C8*3 increases risk of neuropathy in breast cancer patients treated with paclitaxel.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.2013-01-01T00:00:00Z2013 Jun2021-02-19T18:29:43Z2019-03-27T01:10:13ZS-EPMC36600782341328010.1093/annonc/mdt018