Integrin beta-3 L33P: a new insight into the pathogenesis of chronic oxaliplatin-induced peripheral neuropathy?
OBJECTIVE
To assess the significance of the ITGB3 polymorphism at residue 33 (ITGB3 L33P) in the development of chronic oxaliplatin-induced peripheral neuropathy (OXLIPN).


METHODS
Fifty-five patients with advanced colorectal cancer were genotyped, using allele-specific primers and sybr green in real-time PCR. Patients had received adjuvant oxaliplatin-based chemotherapy. The severity of the OXLIPN was defined by means of the clinical total neuropathy score (TNSc). Following the discontinuation of treatment, 34/55 patients (61.8%) developed OXLIPN. Grade I neurotoxicity was revealed in 13 (38.2%) patients and grade II neurotoxicity in 21 (61.8%) patients.


RESULTS
Patients without OXLIPN (n = 21) were 19% homozygous for C, 33.3% were heterozygous, and 47.7% were homozygous for T. The corresponding percentages for patients developing any grade of OXLIPN (n = 34) were similar. About half of patients (46.1%) with grade I OXLIPN were heterozygotes (CT), 23.1% were CC, and 30.8% were TT. The majority of patients with grade II OXLIPN were TT (66.7%) with the remaining 33.3% being CT. The TT genotype was associated with increased severity of OXLIPN compared to the genotypes containing the C allele (P = 0.044).


CONCLUSIONS
The ITGB3 L33P seems to be unrelated to the development of OXLIPN, but it appears to be related to its severity.
Antonacopoulou
A G
AG
Department of Medicine-Division of Clinical Oncology, University Hospital of Patras, Rion-Patras, Greece.
Argyriou
A A
AA
Scopa
C D
CD
Kottorou
A
A
Kominea
A
A
Peroukides
S
S
Kalofonos
H P
HP
D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002908:Chronic Disease; D015179:Colorectal Neoplasms / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D006801:Humans; D007049:Iatrogenic Disease / Q000517:prevention & control; D039661:Integrin beta3 / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000009:adverse effects*; D000077150:Oxaliplatin; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000175:diagnosis* / Q000378:metabolism; D010865:Pilot Projects; D012720:Severity of Illness Index
D000970:Antineoplastic Agents; D039661:Integrin beta3; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin