Identification of 4 autophagy-related genetic variants as risk factors for chronic lymphocytic leukemia.

We also examined their impact on overall survival(OS), time to first treatment (TTFT), autophagy flux, and immune responses.

我们还检查了它们对总生存（OS）、首次治疗时间（TTFT）、自噬流和免疫反应的影响。

A meta-analysisof the 4 populations identified, to our knowledge, for the first time, significant associations between CDKN2A (rs3731204) and BCL2 (rs4940571, rs12457371, and rs1026825) SNPs and CLL risk, with CDKN2A showing the strongest association (P = 1.57 × 10-12).

据我们所知，首次通过四项人群的荟萃分析，发现了CDKN2A (rs3731204)和BCL2 (rs4940571, rs12457371, 和 rs1026825)单核苷酸多态性与慢性淋巴细胞白血病（CLL）风险之间存在显著关联，其中CDKN2A显示出最强的关联性（P = 1.57 × 10^-12）。

We also validated previously reported associations for FAS, BCL2, and BAK1 SNPs with CLL risk (P = 4.73 × 10-21 to 3.39 × 10-9).

我们还验证了先前报道的FAS、BCL2和BAK1单核苷酸多态性与CLL风险之间的关联（P = 4.73 × 10^-21 至 3.39 × 10^-9）。

The CDKN2Ars3731204 and FASrs1926194 SNPs associated with increased CDKN2A and ACTA2 messenger RNA expression levels in the whole blood and/or lymphocytes (P = 5.1 × 10-7, P = 1.58 × 10-21, and P = 7.8 × 10-41), although no significant effect on autophagy flux was observed.

CDKN2Ars3731204和FASrs1926194单核苷酸多态性（SNPs）与全血和/或淋巴细胞中CDKN2A和ACTA2信使RNA表达水平增加相关（P = 5.1 × 10^-7, P = 1.58 × 10^-21, 和 P = 7.8 × 10^-41），尽管对自噬流没有显著影响。

However, associations were found between CDKN2A, BCL2, and FAS SNPs and various T-cell subsets, cytokine production, and circulating concentrations of interferon gamma, tumor necrosis factor-related apoptosis-inducing ligand, CD40, chemokine ligand 20, and interleukin-2 receptor subunit β proteins (P ≤ .005).

然而，发现CDKN2A、BCL2和FAS SNPs与各种T细胞亚群、细胞因子产生以及干扰素γ、肿瘤坏死因子相关凋亡诱导配体、CD40、趋化因子配体20和白细胞介素-2受体亚单位β蛋白的循环浓度之间存在关联（P ≤ .005）。

No significant association was detected between autophagy variants and OS or TTFT, suggesting that these variants drive disease initiation rather than progression.

没有检测到自噬变异与总生存或治疗前时间之间的显著关联，这表明这些变异驱动疾病启动而非进展。

In conclusion, this study identified 4 novel associations for CLL and provided insights into the biological pathways that influence CLL development.

总之，本研究鉴定了4个与慢性淋巴细胞白血病（CLL）相关的新型关联，并提供了影响CLL发展的生物学途径的见解。