Genome-wide meta-analyses identifies novel taxane-induced peripheral neuropathy-associated loci Journal Article

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Authors: Sucheston-Campbell, L. E.; Clay-Gilmour, A. I.; Barlow, W. E.; Budd, G. T.; Stram, D. O.; Haiman, C. A.; Sheng, X.; Yan, L.; Zirpoli, G.; Yao, S.; Jiang, C; Owzar, K; Hershman, D.; Albain, K. S.; Hayes, D. F.; Moore, H. C.; Hobday, T. J.; Stewart, J. A.; Rizvi, A.; Isaacs, C; Salim, M; Gralow, J. R.; Hortobagyi, G. N.; Livingston, R. B.; Kroetz, D. L.; Ambrosone, C. B.
Article Title: Genome-wide meta-analyses identifies novel taxane-induced peripheral neuropathy-associated loci
Abstract: OBJECTIVE: Taxane containing chemotherapy extends survival for breast cancer patients. However, taxane-induced peripheral neuropathy (TIPN) cannot be predicted, prevented or effectively treated. Using genome-wide analyses, we sought to identify common risk variants for TIPN. PATIENTS AND METHODS: Women with high-risk breast cancer enrolled in SWOG 0221 were genotyped using the Illumina 1M chip. Genome-wide analyses were performed in relation to gt;/=grade 3 Common Terminology Criteria for Adverse Events (CTCAE) neuropathy in European and African Americans. Data were meta-analyzed with GW associations of CTCAE gt;/=grade 3 versus /=grade 3 TIPN in 1269 European Americans and 139 African Americans in S0221, was 11.6 and 22.3%, respectively. CALGB 40101 gt;/=grade 3 TOPN was 7.2%. The most significant association with gt;/=grade 3 TIPN was the G allele of rs1858826 in GNGT1 (Pmeta=1.1x10), which showed a decrease in risk of gt;/=grade 3 TIPN (odds ratio=0.29, 95% confidence interval: 0.18-0.46). CONCLUSION: The genetic variants associated with gt;/=grade 3 TIPN are hypothesized to have biochemical functions and reside in and near genes involved in diabetes and diabetic neuropathy. This finding is consistent with results from CALGB 40101 pathway analyses. Larger homogeneous trials with similar dosing and criteria for defining neuropathy are needed to properly assess the relationship of genomics with the neuropathy spectrum.
Journal Title: Pharmacogenetics and genomics
Volume: 28
Issue: 2
ISSN: 1744-6880; 1744-6872
Publisher: Unknown  
Journal Place: United States
Date Published: 2018
Start Page: 49
End Page: 55
Language: eng
DOI/URL:

10.1097/FPC.0000000000000318
Notes: LR: 20180227; GR: R01 CA095222/CA/NCI NIH HHS/United States; JID: 101231005; NIHMS913836; PMCR: 2019/02/01 00:00; 2019/02/01 00:00 [pmc-release]; 2017/12/27 06:00 [entrez]; 2017/12/27 06:00 [pubmed]; 2017/12/27 06:00 [medline]; ppublish