Genetic variation in immune genes and prognosis of locoregionally advanced nasopharyngeal carcinoma

Aim/Background

To explore the association between immune gene polymorphisms and prognosis in patients with locoregionally advanced nasopharyngeal carcinoma (LANPC).

Methods

Forty-three immune genes and 107 potential functional single nucleotide polymorphisms (SNPs) were chosed using the candidate gene approach. The primary endpoint was overall survival (OS). Genotypes were detected by SNP microarray in the training cohort which included 312 LANPC patients. SNPs which were related with OS in the training cohort would be genotyped in the validation cohort (prospectively recruited 420 LANPC patients) by polymerase chain reaction-ligase detection reaction method. The Kaplan–Meier method was used to estimate OS curves, and the log-rank test was used to compare survival curves. Cox proportional hazard model was applied for multivariate analyses. The Hardy–Weinberg equilibrium was determined for each SNP using the χ² test. In order to control the false discovery rate (FDR), the Q value was calculated by R software, with the significance level of 0.10.

Results

Sixteen SNPs from 13 immune genes were associated with OS in the trainning cohort (P_trend ≤0.15). Among them, IL1A rs20540 (3.6%) and CD5 rs2229177 (4.4%) were excluded from further analysis because of their minor allele frequency lower than 0.05. Results from the validation cohort showed that IL16 rs61752774 (P_trend =0.001, Q =0.012), rs8031107 (P_trend =0.008, Q =0.033) and CCR2 rs1799864(P_trend =0.006, Q =0.033)were significantly related with OS. Multivariate analysis showed these three SNPs were independent prognostic factors for OS, and patients carried rs61752774 TT (CC/CT vs. TT: HR =3.146, 95% CI 1.128-8.774, P =0.029), rs8031107 AA (AG/GG vs. AA: HR =2.163, 95% CI 1.274-3.672, P =0.004) or rs1799864 GG (AA/AG vs. GG: HR =2.509, 95% CI 1.296-4.856, P =0.006) had significantly increased death risk. We then calculated individual SNPs score according to the number of risk genotyps they carried. And we found that the SNPs score was an independent prognostic factor for OS, and ROC curve showed that the SNP score was better in predicting survival than clinical stage.

Conclusions

IL-16 rs61752774, IL-16 rs8031107 and CCR2 rs1799864 were novel independent prognostic factors in patients with LANPC.

Clinical trial identification

Disclosure

All authors have declared no conflicts of interest.