The causal associations of 25(OH)D and its metabolites with oropharyngeal cancer risk: a Mendelian randomization study
Background: Previous studies have suggested that there are distinct correlations of 25-hydroxyvitamin D (25(OH)D) and its metabolites with the risk of developing health conditions and cancer; however, the precise nature of these associations in patients with oropharyngeal cancer (OPC) is unknown. O...
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Medical Journals Sweden
2025-07-01
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| Series: | Acta Odontologica Scandinavica |
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| Online Access: | https://medicaljournalssweden.se/actaodontologica/article/view/44053 |
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| author | YaoHui Yu Yu Zhou |
| author_facet | YaoHui Yu Yu Zhou |
| author_sort | YaoHui Yu |
| collection | DOAJ |
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Background: Previous studies have suggested that there are distinct correlations of 25-hydroxyvitamin D (25(OH)D) and its metabolites with the risk of developing health conditions and cancer; however, the precise nature of these associations in patients with oropharyngeal cancer (OPC) is unknown. Our primary objective was to evaluate the causal impact of 25(OH)D and its metabolites, including 25(OH)D3 and its epimer C3-epi-25(OH)D3, on susceptibility to OPC through the use of Mendelian randomization (MR) methodology.
Methods: Mendelian randomization analysis was performed on data from 291 patients with OPC from Europe, North America, and South America using genetic variant strongly related to C3-epi-25(OH)D3, 25(OH)D, and 25(OH)D3 exposure. The primary analytical method for two-sample MR analysis was inverse-variance weighting (IVW); supplemental analyses (weighted median [WM], MR–Egger) were also conducted. Leave-one-out and Cochran’s Q tests were concurrently used as sensitivity analyses to test and adjust for pleiotropy.
Results: Our MR analysis provided evidence suggesting that greater 25(OH)D3 levels are causally associated with a decreased risk of developing OPC within the European population (WM OR = 0.47, 95% CI = 0.24–0.91, p = 0.03). Only one of the 21 MR analyses yielded significant results; for this MR analysis, the IVW results were significant, but subsequent leave-one-out analyses revealed instability in the causal association. However, the association was significant when rs9304669 was excluded (OR = 0.51, 95% CI = 0.28–0.91, p = 0.02), whereas the other results were not statistically significant. The sensitivity analysis indicated that the results were reliable, with no observed heterogeneity or pleiotropy.
Conclusions: There was no evidence that 25(OH)D, 25(OH)D3 or C3-epi-25(OH)D3 levels are associated with OPC risk or that 25OHD supplementation in the general population prevents OPC.
The registration number is INPLASY202490081.
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| format | Article |
| id | doaj-art-677f6de69a6d49e58df366c2feb00df4 |
| institution | DOAJ |
| issn | 0001-6357 1502-3850 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Medical Journals Sweden |
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| series | Acta Odontologica Scandinavica |
| spelling | doaj-art-677f6de69a6d49e58df366c2feb00df42025-08-20T03:13:18ZengMedical Journals SwedenActa Odontologica Scandinavica0001-63571502-38502025-07-018410.2340/aos.v84.44053The causal associations of 25(OH)D and its metabolites with oropharyngeal cancer risk: a Mendelian randomization studyYaoHui Yu0Yu Zhou1Department of Children Stomatology and Oral Prevention, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. ChinaDepartment of Orthodontics, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China Background: Previous studies have suggested that there are distinct correlations of 25-hydroxyvitamin D (25(OH)D) and its metabolites with the risk of developing health conditions and cancer; however, the precise nature of these associations in patients with oropharyngeal cancer (OPC) is unknown. Our primary objective was to evaluate the causal impact of 25(OH)D and its metabolites, including 25(OH)D3 and its epimer C3-epi-25(OH)D3, on susceptibility to OPC through the use of Mendelian randomization (MR) methodology. Methods: Mendelian randomization analysis was performed on data from 291 patients with OPC from Europe, North America, and South America using genetic variant strongly related to C3-epi-25(OH)D3, 25(OH)D, and 25(OH)D3 exposure. The primary analytical method for two-sample MR analysis was inverse-variance weighting (IVW); supplemental analyses (weighted median [WM], MR–Egger) were also conducted. Leave-one-out and Cochran’s Q tests were concurrently used as sensitivity analyses to test and adjust for pleiotropy. Results: Our MR analysis provided evidence suggesting that greater 25(OH)D3 levels are causally associated with a decreased risk of developing OPC within the European population (WM OR = 0.47, 95% CI = 0.24–0.91, p = 0.03). Only one of the 21 MR analyses yielded significant results; for this MR analysis, the IVW results were significant, but subsequent leave-one-out analyses revealed instability in the causal association. However, the association was significant when rs9304669 was excluded (OR = 0.51, 95% CI = 0.28–0.91, p = 0.02), whereas the other results were not statistically significant. The sensitivity analysis indicated that the results were reliable, with no observed heterogeneity or pleiotropy. Conclusions: There was no evidence that 25(OH)D, 25(OH)D3 or C3-epi-25(OH)D3 levels are associated with OPC risk or that 25OHD supplementation in the general population prevents OPC. The registration number is INPLASY202490081. https://medicaljournalssweden.se/actaodontologica/article/view/44053oropharyngeal cancermendelian randomization25(OH)D25(OH)D3C3-epi-25(OH)D3 |
| spellingShingle | YaoHui Yu Yu Zhou The causal associations of 25(OH)D and its metabolites with oropharyngeal cancer risk: a Mendelian randomization study Acta Odontologica Scandinavica oropharyngeal cancer mendelian randomization 25(OH)D 25(OH)D3 C3-epi-25(OH)D3 |
| title | The causal associations of 25(OH)D and its metabolites with oropharyngeal cancer risk: a Mendelian randomization study |
| title_full | The causal associations of 25(OH)D and its metabolites with oropharyngeal cancer risk: a Mendelian randomization study |
| title_fullStr | The causal associations of 25(OH)D and its metabolites with oropharyngeal cancer risk: a Mendelian randomization study |
| title_full_unstemmed | The causal associations of 25(OH)D and its metabolites with oropharyngeal cancer risk: a Mendelian randomization study |
| title_short | The causal associations of 25(OH)D and its metabolites with oropharyngeal cancer risk: a Mendelian randomization study |
| title_sort | causal associations of 25 oh d and its metabolites with oropharyngeal cancer risk a mendelian randomization study |
| topic | oropharyngeal cancer mendelian randomization 25(OH)D 25(OH)D3 C3-epi-25(OH)D3 |
| url | https://medicaljournalssweden.se/actaodontologica/article/view/44053 |
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