Genetically predicted circulating levels of cytokines and the risk of oral cavity and pharyngeal cancer: a bidirectional mendelian-randomization study
Background: Epidemiological research has established associations between various inflammatory cytokines and the occurrence of oral cancer and oropharyngeal cancer (OCPC). We performed a Mendelian randomization (MR) analysis to systematically investigate the causal relationship between inflammatory...
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1321484/full |
| _version_ | 1797357723490189312 |
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| author | Kehan Wu Qianhui Sun Dongxu Liu Jiayi Lu Deyu Wen Xiyan Zang Li Gao |
| author_facet | Kehan Wu Qianhui Sun Dongxu Liu Jiayi Lu Deyu Wen Xiyan Zang Li Gao |
| author_sort | Kehan Wu |
| collection | DOAJ |
| description | Background: Epidemiological research has established associations between various inflammatory cytokines and the occurrence of oral cancer and oropharyngeal cancer (OCPC). We performed a Mendelian randomization (MR) analysis to systematically investigate the causal relationship between inflammatory cytokines and OCPC.Methods: We performed a bidirectional two-sample MR analysis using OCPC from 12 studies (6,034 cases and 6,585 controls) and genome-wide association study (GWAS) results for 41 serum cytokines from 8,293 Finns, respectively. Inverse variance weighting was used as the primary MR method and four additional MR methods (MR Egger, Weighted median, Simple mode, Weighted mode) were used to examine genetic associations between inflammatory traits and OCPC, and Cochran’s Q test, MR-Egger intercept, leave-one-out analysis, funnel plot, and multivariate MR (MVMR) analysis were used to assess the MR results.Results: The results suggested a potential association between high gene expression of Macrophage inflammatory protein-1α (MIP1α/CCL3) and an increased risk of OCPC (Odds Ratio (OR): 1.71, 95% Confidence Interval (CI): 1.09–2.68, p = 0.019). Increasing the expression levels of the interleukin-7 (IL-7) gene by 1 standard deviation reduced the risk of OCPC (OR: 0.64, 95%CI: 0.48–0.86, p = 0.003). In addition, multivariate Mendelian randomization analysis also showed the same results (MIP1α/CCL3, OR: 1.002, 95% CI: 0.919–1.092, p = 0.044; IL-7, OR: 0.997, 95% CI: 0.994–0.999, p = 0.011). Conversely, there was a positive correlation between genetic susceptibility to OCPC and an increase in Interleukin-4 (IL-4) (OR: 1.04, 95%CI: 1.00–1.08, p = 0.027).Conclusion: Our study systematically assessed the association between inflammatory cytokines and the risk of OCPC. We identified two upstream regulatory factors (IL-7 and CCL3) and one downstream effector factor (IL-4) that were associated with OCPC, offering potential avenues for the development of novel treatments. |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-08T14:49:16Z |
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| spelling | doaj.art-ba7821da45d64296b250dcbd4d7b47e72024-01-11T04:38:30ZengFrontiers Media S.A.Frontiers in Genetics1664-80212024-01-011410.3389/fgene.2023.13214841321484Genetically predicted circulating levels of cytokines and the risk of oral cavity and pharyngeal cancer: a bidirectional mendelian-randomization studyKehan Wu0Qianhui Sun1Dongxu Liu2Jiayi Lu3Deyu Wen4Xiyan Zang5Li Gao6Department of Oral and Maxillofacial Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, ChinaDepartment of Oral and Maxillofacial Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, ChinaDepartment of Oral and Maxillofacial Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, ChinaDepartment of Oral and Maxillofacial Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, ChinaDepartment of Oral and Maxillofacial Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, ChinaDepartment of Oral and Maxillofacial Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, ChinaBackground: Epidemiological research has established associations between various inflammatory cytokines and the occurrence of oral cancer and oropharyngeal cancer (OCPC). We performed a Mendelian randomization (MR) analysis to systematically investigate the causal relationship between inflammatory cytokines and OCPC.Methods: We performed a bidirectional two-sample MR analysis using OCPC from 12 studies (6,034 cases and 6,585 controls) and genome-wide association study (GWAS) results for 41 serum cytokines from 8,293 Finns, respectively. Inverse variance weighting was used as the primary MR method and four additional MR methods (MR Egger, Weighted median, Simple mode, Weighted mode) were used to examine genetic associations between inflammatory traits and OCPC, and Cochran’s Q test, MR-Egger intercept, leave-one-out analysis, funnel plot, and multivariate MR (MVMR) analysis were used to assess the MR results.Results: The results suggested a potential association between high gene expression of Macrophage inflammatory protein-1α (MIP1α/CCL3) and an increased risk of OCPC (Odds Ratio (OR): 1.71, 95% Confidence Interval (CI): 1.09–2.68, p = 0.019). Increasing the expression levels of the interleukin-7 (IL-7) gene by 1 standard deviation reduced the risk of OCPC (OR: 0.64, 95%CI: 0.48–0.86, p = 0.003). In addition, multivariate Mendelian randomization analysis also showed the same results (MIP1α/CCL3, OR: 1.002, 95% CI: 0.919–1.092, p = 0.044; IL-7, OR: 0.997, 95% CI: 0.994–0.999, p = 0.011). Conversely, there was a positive correlation between genetic susceptibility to OCPC and an increase in Interleukin-4 (IL-4) (OR: 1.04, 95%CI: 1.00–1.08, p = 0.027).Conclusion: Our study systematically assessed the association between inflammatory cytokines and the risk of OCPC. We identified two upstream regulatory factors (IL-7 and CCL3) and one downstream effector factor (IL-4) that were associated with OCPC, offering potential avenues for the development of novel treatments.https://www.frontiersin.org/articles/10.3389/fgene.2023.1321484/fulloral cavity and pharyngeal cancerinflammation factorscytokinesmendelian randomizationHNSCCgenome-wide association study |
| spellingShingle | Kehan Wu Qianhui Sun Dongxu Liu Jiayi Lu Deyu Wen Xiyan Zang Li Gao Genetically predicted circulating levels of cytokines and the risk of oral cavity and pharyngeal cancer: a bidirectional mendelian-randomization study Frontiers in Genetics oral cavity and pharyngeal cancer inflammation factors cytokines mendelian randomization HNSCC genome-wide association study |
| title | Genetically predicted circulating levels of cytokines and the risk of oral cavity and pharyngeal cancer: a bidirectional mendelian-randomization study |
| title_full | Genetically predicted circulating levels of cytokines and the risk of oral cavity and pharyngeal cancer: a bidirectional mendelian-randomization study |
| title_fullStr | Genetically predicted circulating levels of cytokines and the risk of oral cavity and pharyngeal cancer: a bidirectional mendelian-randomization study |
| title_full_unstemmed | Genetically predicted circulating levels of cytokines and the risk of oral cavity and pharyngeal cancer: a bidirectional mendelian-randomization study |
| title_short | Genetically predicted circulating levels of cytokines and the risk of oral cavity and pharyngeal cancer: a bidirectional mendelian-randomization study |
| title_sort | genetically predicted circulating levels of cytokines and the risk of oral cavity and pharyngeal cancer a bidirectional mendelian randomization study |
| topic | oral cavity and pharyngeal cancer inflammation factors cytokines mendelian randomization HNSCC genome-wide association study |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1321484/full |
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