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<sup>©</sup> (TNSc<sup>©</sup>). None of the polymorphisms investigated was found associated with grade ≥ chronic OXAIPN (NCI-CTC criteria), while a nominal association emerged for ACYP2 rs843748 when using the TNSc<sup>©</sup> 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.

Terrazzino, S., Argyriou, A., Cargnin, S., Antonacopoulou, A., Briani, C., Bruna, J., et al. (2015). Genetic determinants of chronic oxaliplatin-induced peripheral neurotoxicity: A genome-wide study replication and meta-analysis. JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, 20(1), 15-23 [10.1111/jns.12110].

Genetic determinants of chronic oxaliplatin-induced peripheral neurotoxicity: A genome-wide study replication and meta-analysis

ALBERTI, PAOLA;CORTINOVIS, DIEGO LUIGI;CAZZANIGA, MARINA ELENA;CAVALETTI, GUIDO ANGELO
Ultimo
2015

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 ≥ 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.
Articolo in rivista - Articolo scientifico
chemotherapy-induced peripheral neuropathy; meta-analysis; neurotoxicity; oxaliplatin; polymorphisms
English
2015
20
1
15
23
none
Terrazzino, S., Argyriou, A., Cargnin, S., Antonacopoulou, A., Briani, C., Bruna, J., et al. (2015). Genetic determinants of chronic oxaliplatin-induced peripheral neurotoxicity: A genome-wide study replication and meta-analysis. JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, 20(1), 15-23 [10.1111/jns.12110].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/80776
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