CYP2C8*3 increases risk of neuropathy in breast cancer patients treated with paclitaxel
CYP2C8*3 increases risk of neuropathy in breast cancer patients treated with paclitaxel
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DOI：
10.1093/annonc/mdt018
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发表时间：
2013-06-01
影响因子：
50.5
通讯作者：
Dees, E. C.
中科院分区：
文献类型：
--
作者：
Hertz, D. L.;Roy, S.;Dees, E. C.
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% Cl: 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.
