Association between Genetic Variants and Peripheral Neuropathy in Patients with NSCLC Treated with First-Line...

Area of Science:

• Oncology
• Pharmacogenomics
• Neuroscience

Background:

• Chemotherapy-induced peripheral neuropathy (CIPN) is a common and disabling side effect for non-small cell lung cancer (NSCLC) patients receiving platinum-based chemotherapy.
• Genetic variants are increasingly recognized as contributors to CIPN susceptibility.

Purpose of the Study:

• To investigate genetic risk factors for CIPN in NSCLC patients.
• To explore previously reported genetic associations with CIPN susceptibility.

Main Methods:

• A multicenter prospective follow-up study (PGxLUNG) enrolled NSCLC patients (stage II-IV) receiving first-line platinum-based chemotherapy.
• Clinical neuropathy evaluation (CTCAE v4.03) was conducted at multiple time points.
• Logistic regression analysis assessed the relationship between 34 single nucleotide polymorphisms (SNPs) in 26 genes and CIPN (any grade and severe grade).

Main Results:

• Out of 320 patients, 26.3% experienced any grade CIPN and 8.1% experienced severe CIPN.
• The GG-genotype of TRPV1 (rs879207) was associated with a 5.2-fold increased risk of severe neuropathy (OR 5.2, 95%CI 2.1−12.8, p=0.012).
• Multivariate analysis confirmed the association of the GG-genotype (ORadj 4.7) and paclitaxel use (ORadj 7.2) with severe CIPN.

Conclusions:

• Patients with the TRPV1 GG-genotype (rs879207) exhibit a nearly 5-fold higher risk of severe neuropathy from platinum-based therapy.
• Validation in independent cohorts is recommended.
• Findings may inform the individualization of platinum-based chemotherapy regimens.