Scholarlink

Background <p>This Mendelian randomization (MR) study aimed to investigate bidirectional causal relationships between genetically predicted iron homeostasis, mitochondrial function, and the risk of laryngeal and hypopharyngeal cancers.</p> Methods <p>Summary-level data were extracted from genome-wide association studies (GWAS) of iron status, mitochondrial function, laryngeal and hypopharyngeal cancers were analyzed. Two-sample MR analyses were performed using inverse variance weighted (IVW), weighted median, weighted mode, and MR-Egger regression. Sensitivity analyses incorporated MR-Egger intercept, MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO), Cochran’s Q test, and leave-one-out validation.</p> Results <p>MR analysis identified a significant association between the mitochondrial sirtuin-5 (NAD-dependent protein deacylase) and the elevated risk of hypopharyngeal cancer (OR = 2, 95% CI: 1.06–3.76, <i>P</i> = 0.03). Reverse MR analyses demonstrated that larynx cancer inversely correlated with transferrin saturation (OR = 0.992, 95% CI: 0.987–0.998, <i>P</i> &lt; 0.001) and persulfide dioxygenase ETHE1 (OR = 0.95, 95% CI: 0.92–0.98, <i>P</i> &lt; 0.001). In addition, no causal effect of iron status on the risk of laryngeal and hypopharyngeal cancers (All <i>P</i> &gt; 0.05). Sensitivity analyses confirmed results robustness with no evidence of pleiotropy and heterogeneity.</p> Conclusion <p>Our findings reveal a novel pathogenic role of sirtuin-5 in hypopharyngeal cancer, suggesting its potential as a therapeutic target. Conversely, laryngeal cancer might slightly affect transferrin saturation and ETHE1, indicating their utility as diagnostic markers for laryngeal cancer. Future mechanistic studies are warranted to elucidate these complex associations.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Causal links between iron status, mitochondrial function, and laryngeal and hypopharyngeal cancers: a Mendelian study

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月16日

查看全文
  • Jiandong Zhao,
  • Liwei Chen,
  • Bing Han,
  • Siyang Li,
  • Yongxia Zhang,
  • Ge Gao,
  • Jinjing Liu

摘要

Background

This Mendelian randomization (MR) study aimed to investigate bidirectional causal relationships between genetically predicted iron homeostasis, mitochondrial function, and the risk of laryngeal and hypopharyngeal cancers.

Methods

Summary-level data were extracted from genome-wide association studies (GWAS) of iron status, mitochondrial function, laryngeal and hypopharyngeal cancers were analyzed. Two-sample MR analyses were performed using inverse variance weighted (IVW), weighted median, weighted mode, and MR-Egger regression. Sensitivity analyses incorporated MR-Egger intercept, MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO), Cochran’s Q test, and leave-one-out validation.

Results

MR analysis identified a significant association between the mitochondrial sirtuin-5 (NAD-dependent protein deacylase) and the elevated risk of hypopharyngeal cancer (OR = 2, 95% CI: 1.06–3.76, P = 0.03). Reverse MR analyses demonstrated that larynx cancer inversely correlated with transferrin saturation (OR = 0.992, 95% CI: 0.987–0.998, P < 0.001) and persulfide dioxygenase ETHE1 (OR = 0.95, 95% CI: 0.92–0.98, P < 0.001). In addition, no causal effect of iron status on the risk of laryngeal and hypopharyngeal cancers (All P > 0.05). Sensitivity analyses confirmed results robustness with no evidence of pleiotropy and heterogeneity.

Conclusion

Our findings reveal a novel pathogenic role of sirtuin-5 in hypopharyngeal cancer, suggesting its potential as a therapeutic target. Conversely, laryngeal cancer might slightly affect transferrin saturation and ETHE1, indicating their utility as diagnostic markers for laryngeal cancer. Future mechanistic studies are warranted to elucidate these complex associations.