Causal links between iron status, mitochondrial function, and laryngeal and hypopharyngeal cancers: a Mendelian study
Abstract 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...
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| Format: | Article |
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Springer
2025-07-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-03187-7 |
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| author | Jiandong Zhao Liwei Chen Bing Han Siyang Li Yongxia Zhang Ge Gao Jinjing Liu |
| author_facet | Jiandong Zhao Liwei Chen Bing Han Siyang Li Yongxia Zhang Ge Gao Jinjing Liu |
| author_sort | Jiandong Zhao |
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| description | Abstract 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. |
| format | Article |
| id | doaj-art-754f296d597c4e4c82c8f591e27aa486 |
| institution | Kabale University |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-754f296d597c4e4c82c8f591e27aa4862025-08-20T04:02:54ZengSpringerDiscover Oncology2730-60112025-07-0116111810.1007/s12672-025-03187-7Causal links between iron status, mitochondrial function, and laryngeal and hypopharyngeal cancers: a Mendelian studyJiandong Zhao0Liwei Chen1Bing Han2Siyang Li3Yongxia Zhang4Ge Gao5Jinjing Liu6Senior Department of Otolaryngologeal Head and Neck Surgery, The 6th Medical Center of Chinese PLA General HospitalSenior Department of Otolaryngologeal Head and Neck Surgery, The 6th Medical Center of Chinese PLA General HospitalSenior Department of Otolaryngologeal Head and Neck Surgery, The 6th Medical Center of Chinese PLA General HospitalSenior Department of Otolaryngologeal Head and Neck Surgery, The 6th Medical Center of Chinese PLA General HospitalSenior Department of Otolaryngologeal Head and Neck Surgery, The 6th Medical Center of Chinese PLA General HospitalSenior Department of Otolaryngologeal Head and Neck Surgery, The 6th Medical Center of Chinese PLA General HospitalSenior Department of Otolaryngologeal Head and Neck Surgery, The 6th Medical Center of Chinese PLA General HospitalAbstract 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.https://doi.org/10.1007/s12672-025-03187-7Mendelian randomizationIron metabolismMitochondrial functionLaryngeal cancerHypopharyngeal cancerSirtuin-5 |
| spellingShingle | Jiandong Zhao Liwei Chen Bing Han Siyang Li Yongxia Zhang Ge Gao Jinjing Liu Causal links between iron status, mitochondrial function, and laryngeal and hypopharyngeal cancers: a Mendelian study Discover Oncology Mendelian randomization Iron metabolism Mitochondrial function Laryngeal cancer Hypopharyngeal cancer Sirtuin-5 |
| title | Causal links between iron status, mitochondrial function, and laryngeal and hypopharyngeal cancers: a Mendelian study |
| title_full | Causal links between iron status, mitochondrial function, and laryngeal and hypopharyngeal cancers: a Mendelian study |
| title_fullStr | Causal links between iron status, mitochondrial function, and laryngeal and hypopharyngeal cancers: a Mendelian study |
| title_full_unstemmed | Causal links between iron status, mitochondrial function, and laryngeal and hypopharyngeal cancers: a Mendelian study |
| title_short | Causal links between iron status, mitochondrial function, and laryngeal and hypopharyngeal cancers: a Mendelian study |
| title_sort | causal links between iron status mitochondrial function and laryngeal and hypopharyngeal cancers a mendelian study |
| topic | Mendelian randomization Iron metabolism Mitochondrial function Laryngeal cancer Hypopharyngeal cancer Sirtuin-5 |
| url | https://doi.org/10.1007/s12672-025-03187-7 |
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