Introduction: Autophagy not only plays an important role in the progression of cancer but is also involved in tissue inflammatory response. However, few published studies have investigated associations between functional genetic variants of autophagy‐related genes and radiation pneumonitis (RP) as well as clinical outcomes in patients with NSCLC after definitive radiotherapy. Methods: We genotyped nine potentially functional single‐nucleotide polymorphisms (SNPs) in four autophagy‐related genes (autophagy related 2B gene [ATG2B], autophagy related 10 gene [ATG10], autophagy related 12 gene [ATG12], and autophagy related 16 like 2 gene [ATG16L2]) in 393 North American patients with NSCLC treated by definitive radiotherapy and assessed their associations with RP, local recurrence‐free survival (LRFS), progression‐free survival (PFS), and overall survival (OS) in multivariable Cox proportional hazard regression analyses. Results: We found that patients with the ATG16L2 rs10898880 CC variant genotype had a better LRFS, PFS, and OS (adjusted hazard ratio = 0.59, 0.64, and 0.64; 95% confidence interval: 0.45–0.79, 0.48–0.84, and 0.48–0.86; p = 0.0004, 0.002, and 0.003, respectively), but a greater risk for development of severe RP (adjusted hazard ratio = 1.80, 95% confidence interval: 1.04–3.12, p = 0.037) than did patients with AA/AC genotypes. Further functional analyses suggested that the ATG16L2 rs10898880 C variant allele modulated expression of the ATG16L2 gene. Conclusion: This is the first report that one potentially functional SNP rs10898880 in ATG16L2 may be a predictor of RP, LRFS, PFS, and OS in patients with NSCLC after definitive radiotherapy. Additional larger, prospective studies are needed to confirm these findings.

中文翻译：

---

ATG16L2 的潜在功能变异可预测非小细胞肺癌患者根治性放疗后的放射性肺炎和预后

简介：自噬不仅在癌症的发展中起重要作用，而且还参与组织炎症反应。然而，很少有已发表的研究调查了自噬相关基因的功能性遗传变异与放射性肺炎 (RP) 以及 NSCLC 患者根治性放疗后临床结果之间的关联。方法：我们对四个自噬相关基因（自噬相关 2B 基因 [ATG2B]、自噬相关 10 基因 [ATG10]、自噬相关 12 基因 [ATG12] 和自噬相关 16 基因）中的 9 个潜在功能性单核苷酸多态性 (SNP) 进行基因分型2 基因 [ATG16L2]) 在 393 名接受根治性放疗的北美 NSCLC 患者中进行，并评估了它们与 RP、局部无复发生存期 (LRFS)、无进展生存期 (PFS)、和多变量 Cox 比例风险回归分析中的总生存期 (OS)。结果：我们发现具有 ATG16L2 rs10898880 CC 变异基因型的患者具有更好的 LRFS、PFS 和 OS（调整后的风险比 = 0.59、0.64 和 0.64；95% 置信区间：0.45–0.79、0.48–0.484 0.86；分别为 p = 0.0004、0.002 和 0.003），但与 AA/AC 患者相比，发生严重 RP 的风险更大（调整后的风险比 = 1.80，95% 置信区间：1.04-3.12，p = 0.037）基因型。进一步的功能分析表明，ATG16L2 rs10898880 C 变异等位基因调节了 ATG16L2 基因的表达。结论：这是首次报道 ATG16L2 中一个潜在功能性 SNP rs10898880 可能是 NSCLC 患者根治性放疗后 RP、LRFS、PFS 和 OS 的预测因子。额外的更大，