Association of genetic variants in autophagy-lysosome pathway genes with susceptibility and survival to prostate cancer,Gene

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Association of genetic variants in autophagy-lysosome pathway genes with susceptibility and survival to prostate cancer
Gene ( IF 2.6 ) Pub Date : 2021-09-06 , DOI: 10.1016/j.gene.2021.145953
Qiuyuan Zhu ₁ , Yixuan Meng ₂ , Shuwei Li ₂ , Junyi Xin ₂ , Mulong Du ₃ , Meilin Wang ₂ , Gong Cheng ₄

Affiliation

Background

Previous studies have indicated the connections between autophagy-lysosome pathway genes dysfunction and prostate cancer, but few studies have investigated whether single nucleotide polymorphisms (SNPs) in autophagy-lysosome pathway genes are implicated in prostate cancer risk and survival.

Materials and methods

Logistic regression analysis and stepwise Cox regression analysis were conducted in 4,662 cases and 3,114 controls from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. The false positive rate probability (FPRP) method was applied to correct for multiple comparisons. Gene-based analysis was calculated by versatile gene-based association study approach.

Results

We found that SLC11A1 rs7573065 significantly increased the risk of prostate cancer [adjusted odds ratio (OR) = 1.24, 95% confidence interval (CI) = 1.06–1.46, P = 7.02 × 10⁻³, FPRP = 0.082]. Furthermore, rs7573065 was confirmed as the independent predicator of overall survival (OS) for prostate cancer patients [Hazard ratio (HR) = 1.30, 95% CI = 1.01–1.66, P = 0.041]. The significant association between SLC11A1 and prostate cancer risk was calculated by gene-based analysis (P = 0.030). We also observed that the mRNA of SLC11A1 in prostate tumor tissues was significantly over-expressed than that in normal tissues.

Conclusion

This study suggested that rs7573065 in SLC11A1 was associated with an increased risk and poor OS of prostate cancer. Our findings may provide evidence for genetic variants in autophagy-lysosome pathway as the risk and prognostic biomarkers for prostate cancer.

中文翻译：

自噬-溶酶体通路基因的遗传变异与前列腺癌的易感性和存活率的关联

背景

先前的研究表明自噬-溶酶体通路基因功能障碍与前列腺癌之间存在联系，但很少有研究调查自噬-溶酶体通路基因中的单核苷酸多态性 (SNP) 是否与前列腺癌风险和生存有关。

材料和方法

对来自前列腺、肺、结直肠和卵巢 (PLCO) 癌症筛查试验的 4,662 例病例和 3,114 例对照进行了逻辑回归分析和逐步 Cox 回归分析。应用假阳性率概率 (FPRP) 方法来校正多重比较。基于基因的分析是通过通用的基于基因的关联研究方法计算的。

结果

我们发现SLC11A1 rs7573065 显着增加了患前列腺癌的风险 [调整后的优势比 (OR) = 1.24，95% 置信区间 (CI) = 1.06–1.46，P = 7.02 × 10 ^-3，FPRP = 0.082]。此外，rs7573065 被确认为前列腺癌患者总生存期 (OS) 的独立预测因子 [危险比 (HR) = 1.30，95% CI = 1.01–1.66，P = 0.041]。SLC11A1与前列腺癌风险之间的显着关联是通过基于基因的分析计算得出的（P = 0.030）。我们还观察到前列腺肿瘤组织中SLC11A1的 mRNA比正常组织中显着过度表达。