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- Title
Genetic determinants of chronic oxaliplatin-induced peripheral neurotoxicity: a genome-wide study replication and meta-analysis.
- Authors
Terrazzino, Salvatore; Argyriou, Andreas A.; Cargnin, Sarah; Antonacopoulou, Anna G.; Briani, Chiara; Bruna, Jordi; Velasco, Roser; Alberti, Paola; Campagnolo, Marta; Lonardi, Sara; Cortinovis, Diego; Cazzaniga, Marina; Santos, Cristina; Kalofonos, Haralabos P.; Canonico, Pier Luigi; Genazzani, Armando A.; Cavaletti, Guido
- Abstract
We aimed at validating the role of genetic variants identified by a recent genome-wide association study (GWAS) as determinants of chronic oxaliplatin-induced peripheral neurotoxicity ( OXAIPN). Eight polymorphisms (rs10486003, rs2338, rs843748, rs797519, rs4936453, rs12023000, rs17140129, and rs6924717) were genotyped in a total of 150 colorectal cancer patients of Caucasian origin receiving oxaliplatin-based chemotherapy. The severity grade of chronic OXAIPN was assessed by NCI-CTC criteria and the clinical version of the Total Neuropathy Score© ( TNSc©). None of the polymorphisms investigated was found associated with grade ≥ 2 chronic OXAIPN ( NCI-CTC criteria), while a nominal association emerged for ACYP2 rs843748 when using the TNSc© scale (dominant model: odds ratio [ OR]: 0.27, 95% confidence interval [ CI]: 0.10-0.75, P = 0.008). In the combined analysis of this results with data of the two previously published studies which assessed chronic OXAIPN by NCI-CTC criteria, evidence suggestive of association with chronic OXAIPN ( NCI-CTC criteria) was found for ACYP2 rs843748 (dominant model: OR: 2.40, 95% CI: 1.40-5.24, P = 0.027), which, however, did not remain significant after correction for multiple testing (threshold P-value <0.00625). These findings suggest a minor role of the single nucleotide polymorphisms ( SNPs) investigated as genetic determinants of chronic OXAIPN. These results also highlight the importance of replication studies with meta-analysis for validation of GWAS findings.
- Subjects
CANCER chemotherapy; CANCER patients; COLON tumors; CONFIDENCE intervals; GENETIC polymorphisms; PERIPHERAL neuropathy; NEUROTOXICOLOGY; RECTUM tumors; OXALIPLATIN; SYNDROMES; ODDS ratio; GENOTYPES; DISEASE risk factors
- Publication
Journal of the Peripheral Nervous System, 2015, Vol 20, Issue 1, p15
- ISSN
1085-9489
- Publication type
Article
- DOI
10.1111/jns.12110