Genetic associations of LXN polymorphisms with toxicities of platinum-based concurrent chemoradiotherapy of nasopharyngeal carcinoma.

PURPOSE: Oral mucositis (OM) is a common and debilitating adverse effect associated with chemoradiotherapy in nasopharyngeal carcinoma. This study aimed to investigate the association between Latexin (LXN) polymorphism and acute toxicity of oral mucositis.

METHODS

A total of 238 nasopharyngeal carcinoma (NPC) patients were enrolled. LXN genotypes were analyzed by the Sequenom MassARRAY system. Multivariate logistic regression was performed to assess the association of LXN polymorphisms and chemoradiotherapy-induced toxicities. Multifactor and generalized multifactor dimensionality reduction methods were applied to calculate the SNP-SNP interaction.

RESULTS

Our study showed that the frequency of the AG genotype of rs1492908 was significantly lower in the grade 3-4 oral mucositis group compared to the grade 0-2 group (14.1% vs. 27.1%, respectively). Patients carrying the LXN rs1492908 AG genotype exhibited a decreased risk of severe oral mucositis (OR = 0.452, 95% CI = 0.213-0.959, P = 0.039). Stratification analysis further revealed that the rs1492908 AG genotype conferred protective effects against oral mucositis in specific patient populations, including those aged ≥ 47 years (OR = 0.340, P = 0.041), body mass index (BMI) ≥ 24 (OR = 0.286, P = 0.035), WHO type Ⅲ histology (OR = 0.212, P = 0.007), and receiving a higher radiotherapy dose (planning gross tumor volume of nasopharynx (pGTVnx) ≥ 71 Gy) (OR = 0.158, P = 0.016). Additionally, SNP-SNP interaction analysis identified that the combination of rs1492908, rs9841, rs8455, rs2639655, and rs56321207 was the best multi-locus model for oral mucositis.

CONCLUSION

This study is the first to establish a link between NPC chemoradiotherapy-induced oral mucositis risk and LXN polymorphisms in the Chinese Han population.