TY - JOUR
T1 - Genetic determinants of chronic oxaliplatin-induced peripheral neurotoxicity
T2 - A genome-wide study replication and meta-analysis
AU - Terrazzino, Salvatore
AU - Argyriou, Andreas A.
AU - Cargnin, Sarah
AU - Antonacopoulou, Anna G.
AU - Briani, Chiara
AU - Bruna, Jordi
AU - Velasco, Roser
AU - Alberti, Paola
AU - Campagnolo, Marta
AU - Lonardi, Sara
AU - Cortinovis, Diego
AU - Cazzaniga, Marina
AU - Santos, Cristina
AU - Kalofonos, Haralabos P.
AU - Canonico, Pier Luigi
AU - Genazzani, Armando A.
AU - Cavaletti, Guido
N1 - Publisher Copyright:
© 2015 Peripheral Nerve Society.
PY - 2015/3/1
Y1 - 2015/3/1
N2 - 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.
AB - 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.
KW - chemotherapy-induced peripheral neuropathy
KW - meta- analysis
KW - neurotoxicity
KW - oxaliplatin
KW - polymorphisms
UR - https://www.scopus.com/pages/publications/84930973584
U2 - 10.1111/jns.12110
DO - 10.1111/jns.12110
M3 - Article
SN - 1085-9489
VL - 20
SP - 15
EP - 23
JO - Journal of the Peripheral Nervous System
JF - Journal of the Peripheral Nervous System
IS - 1
ER -
