Causal association between radiation exposure and risk of head and neck cancer: a Mendelian randomization study_West China Medical Journal

Authors：

DING Yunhan ¹ , ZHANG Shasha ² , ZHAO Xiaoxiao ³ , KE Lixin ⁴ , XIE Shoujun ¹ ,  SUN Qiyu ¹ ,  LU Cuncun ⁵

1. Department of Clinical Laboratory, Affiliated Hospital of Chengde Medical University (Nanyuan District), Chengde, Hebei 067000, P. R. China;
2. Institute of Genetics, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu 730000, P. R. China;
3. Geriatric Medicine Center, Affiliated Hospital of Shandong University of TCM, Jinan, Shandong 250014, P. R. China;
4. Department of Pediatrics, University of Groningen, Groningen 9713GZ, Netherlands;
5. School of Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu 730101, P. R. China;

Corresponding author：

SUN Qiyu, Email: Sunqiyu063017@163.com; LU Cuncun, Email: lu17metrics@163.com

Keywords：

Radiation exposure; head and neck cancer; instrumental variable; causal inference; Mendelian randomization

DOI：

10.7507/1002-0179.202411026

Video：

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Objective To explore the causal association between radiation exposure and risk of head and neck cancer using Mendelian randomization (MR) method. Methods Genome-wide association studies of radiation exposure and head and neck cancer in the public database IEU OpenGWAS were identified, and single nucleotide polymorphisms (SNPs) were screened as instrumental variables. Two-sample MR analyses were performed using random-effect inverse variance weighted (IVW), fixed-effect IVW, weighted median, and MR-Egger methods to assess the causal association between radiation exposure and risk of head and neck cancer. Outliers were tested using the MR-PRESSO method, and heterogeneity was assessed using the Cochran Q test. MR-Egger regression intercept was utilized to detect gene-level pleiotropy, and a leave-one-out sensitivity analysis was conducted to evaluate the robustness of the study results. Results 96 valid SNPs were included as instrumental variables. The analysis results of random-effect IVW method, fixed-effect IVW method, and weighted median method all showed that radiation exposure was associated with an increased risk of head and neck cancer [odds ratio and 95% confidence interval: 1.139 (1.065, 1.218), 1.139 (1.068, 1.215), and 1.141 (1.039, 1.253); P<0.05]. Heterogeneity testing did not reveal significant heterogeneity, MR-Egger regression analysis did not find gene level pleiotropy, and the leave-one-out method did not find a single SNP significantly affecting the overall estimation results. Conclusion Radiation exposure increases the risk of head and neck cancer, but this conclusion still needs further validation in more high-quality, large sample studies.

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7.	卢存存, 陈子佳, 王志飞. 基于真实世界数据的观察性因果推断研究新框架(目标试验模拟)及其在中医药领域中的应用展望. 协和医学杂志, 2024, 15(2): 422-428.
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16.	Falcioni L, Bua L, Tibaldi E, et al. Report of final results regarding brain and heart tumors in Sprague-Dawley rats exposed from prenatal life until natural death to mobile phone radiofrequency field representative of a 1.8 GHz GSM base station environmental emission. Environ Res, 2018, 165: 496-503.
17.	Hong JY, Han K, Jung JH, et al. Association of exposure to diagnostic low-dose ionizing radiation with risk of cancer among youths in South Korea. JAMA Netw Open, 2019, 2(9): e1910584.
18.	Withrow DR, Anderson H, Armstrong GT, et al. Pooled analysis of meningioma risk following treatment for childhood cancer. JAMA Oncol, 2022, 8(12): 1756-1764.
19.	Yuan Y, Sun P, Xiao H, et al. Risk of second primary thyroid cancer in cancer survivors. Sci Rep, 2024, 14(1): 12478.

1. Chow LQM. Head and neck cancer. N Engl J Med, 2020, 382(1): 60-72.
2. Johnson DE, Burtness B, Leemans CR, et al. Head and neck squamous cell carcinoma. Nat Rev Dis Primers, 2020, 6(1): 92.
3. 张少秋, 燕丽, 李瑞辰, 等. 头颈部鳞状细胞癌免疫微环境及其作用机制的最新研究进展及展望. 中国癌症杂志, 2023, 33(6): 629-636.
4. Sadetzki S, Chetrit A, Freedman L, et al. Long-term follow-up for brain tumor development after childhood exposure to ionizing radiation for tinea capitis. Radiat Res, 2005, 163(4): 424-432.
5. Richardson DB, Leuraud K, Laurier D, et al. Cancer mortality after low dose exposure to ionising radiation in workers in France, the United Kingdom, and the United States (INWORKS): cohort study. BMJ, 2023, 382: e074520.
6. Liu Y, Liu Z, Chen J, et al. Personal history of irradiation and risk of breast cancer: a Mendelian randomisation study. J Glob Health, 2024, 14: 04106.
7. 卢存存, 陈子佳, 王志飞. 基于真实世界数据的观察性因果推断研究新框架(目标试验模拟)及其在中医药领域中的应用展望. 协和医学杂志, 2024, 15(2): 422-428.
8. Levin MG, Burgess S. Mendelian randomization as a tool for cardiovascular research: a review. JAMA Cardiol, 2024, 9(1): 79-89.
9. Burgess S, Woolf B, Mason AM, et al. Addressing the credibility crisis in Mendelian randomization. BMC Med, 2024, 22(1): 374.
10. Lu C, Ke L, Mentis AA, et al. Tea intake and non-alcoholic fatty liver disease risk: a two-sample Mendelian randomization study. Metabol Open, 2024, 24: 100322.
11. 尚文茹, 魏莉莉, 卢存存. 受教育程度对系统性红斑狼疮的因果效应: 孟德尔随机化研究. 华西医学, 2023, 38(12): 1880-1884.
12. 高雪, 王慧, 王彤. 孟德尔随机化中多效性偏倚校正方法简介. 中华流行病学杂志, 2019, 40(3): 360-365.
13. Gormley M, Creaney G, Schache A, et al. Reviewing the epidemiology of head and neck cancer: definitions, trends and risk factors. Br Dent J, 2022, 233(9): 780-786.
14. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
15. Xie J, Huang H, Liu Z, et al. The associations between modifiable risk factors and nonalcoholic fatty liver disease: a comprehensive Mendelian randomization study. Hepatology, 2023, 77(3): 949-964.
16. Falcioni L, Bua L, Tibaldi E, et al. Report of final results regarding brain and heart tumors in Sprague-Dawley rats exposed from prenatal life until natural death to mobile phone radiofrequency field representative of a 1.8 GHz GSM base station environmental emission. Environ Res, 2018, 165: 496-503.
17. Hong JY, Han K, Jung JH, et al. Association of exposure to diagnostic low-dose ionizing radiation with risk of cancer among youths in South Korea. JAMA Netw Open, 2019, 2(9): e1910584.
18. Withrow DR, Anderson H, Armstrong GT, et al. Pooled analysis of meningioma risk following treatment for childhood cancer. JAMA Oncol, 2022, 8(12): 1756-1764.
19. Yuan Y, Sun P, Xiao H, et al. Risk of second primary thyroid cancer in cancer survivors. Sci Rep, 2024, 14(1): 12478.

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