Abstract
Background
Thyroid cancer and educational attainment have been related in observational studies. It is unclear if these correlations indicate causative relationships.
Methods
Using large-scale genome-wide association studies (GWAS) datasets, we conducted an univariable and multivariable Mendelian randomization (MR) study to assess a potential connection between educational attainment and thyroid cancer. The inverse-variance weighted (IVW) analysis method is used as our primary outcome. Additionally, we carry out several sensitivity analyses to evaluate the pleiotropy and robustness of the causal estimates.
Results
Univariate MR study shows 4.2 years of additional education is associated with a 41.4% reduction in thyroid cancer risk (OR = 0.586; 95% CI: 0.378–0.909; P = 0.017). Further multivariable MR analysis revealed that body mass index (BMI) acted as a partial mediating factor in the protective impact of higher educational attainment against thyroid cancer.
Conclusion
This MR study provided genetic evidence that longer education attainment is related to a lower risk of thyroid cancer. Strategies of expanding education may reduce the burden of thyroid cancer in the world.
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Data availability
The GWAS summary data utilized in this study are all publicly available.
References
H. Sung, J. Ferlay, R.L. Siegel et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71, 209–249 (2021)
R.L. Siegel, K.D. Miller, H.E. Fuchs et al. Cancer statistics, 2022. Ca Cancer J. Clin. 72, 7–33 (2022)
N. Uppal, C. Cunningham Nee Lubitz, B. James, The cost and financial burden of thyroid cancer on patients in the US: a review and directions for future research. JAMA Otolaryngol.- Head Neck Surg. 148, 568–575 (2022)
H. Sadeghi, M. Rafei, M. Bahrami et al. Attributable risk fraction of four lifestyle risk factors of thyroid cancer: a meta-analysis. J. Public Health 40, e91–e98 (2018)
E. Bandurska-Stankiewicz, E. Aksamit-Białoszewska, J. Rutkowska et al. Effect of individual and socio-economic risk factors on the incidence of thyroid carcinoma in Olsztyn province. Endokrynol. Pol. 61, 671–682 (2010)
V. Zivaljevic, N. Slijepcevic, I. Paunovic et al. Risk factors for anaplastic thyroid cancer. Int. J. Endocrinol. 2014, 815070 (2014)
M.T. Parad, M. Fararouei, A.R. Mirahmadizadeh et al. Thyroid cancer and its associated factors: a population-based case-control study. Int. J. Cancer 149, 514–521 (2021)
L.-A. Jj, X. C, O. Rm et al. Environmental, lifestyle, and anthropometric risk factors for differentiated thyroid cancer in Cuba: a case-control study. Eur. Thyroid J. 3, 189–196 (2014). https://doi.org/10.1159/000362928
S.M. Sørensen, C.D. de la Cour, T. Maltesen et al. Temporal trends in papillary and follicular thyroid cancer incidence from 1995 to 2019 in adults in Denmark according to education and income. Thyroid 32, 972–982 (2022)
G.D. Smith, S. Ebrahim, Mendelian randomization”: can genetic epidemiology contribute to understanding environmental determinants of disease? Int. J. Epidemiol. 32, 1–22 (2003)
S.C. Larsson, H.S. Markus, Genetic liability to insomnia and cardiovascular disease risk. Circulation 140, 796–798 (2019)
T. Tillmann, J. Vaucher, A. Okbay et al. Education and coronary heart disease: mendelian randomisation study. BMJ 358, j3542 (2017)
G. Davey Smith, G. Hemani, Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum. Mol. Genet. 23, R89–R98 (2014)
N.M. Davies, M.V. Holmes, G. Davey Smith, Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ (Clin. Res. ed.) 362, k601 (2018)
C.A. Emdin, A.V. Khera, P. Natarajan et al. Genetic association of waist-to-hip ratio with cardiometabolic traits, type 2 diabetes, and coronary heart disease. JAMA 317, 626–634 (2017)
J.J. Lee, R. Wedow, A. Okbay et al. Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals. Nat. Genet. 50, 1112–1121 (2018)
R. Feng, M. Lu, J. Xu et al. Pulmonary embolism and 529 human blood metabolites: genetic correlation and two-sample Mendelian randomization study. BMC Genom. Data 23, 69 (2022)
S. Burgess, S.G. Thompson, C.R.P. CHD,Genetics Collaboration, Avoiding bias from weak instruments in Mendelian randomization studies. Int. J. Epidemiol. 40, 755–764 (2011).
S. Burgess, A. Butterworth, S.G. Thompson, Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol. 37, 658–665 (2013)
S. Burgess, D.J. Thompson, J.M.B. Rees et al. Dissecting causal pathways using mendelian randomization with summarized genetic data: application to age at menarche and risk of breast cancer. Genetics 207, 481–487 (2017)
S. Burgess, S.G. Thompson, Multivariable Mendelian randomization: the use of pleiotropic genetic variants to estimate causal effects. Am. J. Epidemiol. 181, 251–260 (2015)
N.M. Davies, W.D. Hill, E.L. Anderson et al. Multivariable two-sample Mendelian randomization estimates of the effects of intelligence and education on health. Elife 8, e43990 (2019)
E. Sanderson, G. Davey Smith, F. Windmeijer et al. An examination of multivariable Mendelian randomization in the single-sample and two-sample summary data settings. Int. J. Epidemiol. 48, 713–727 (2019)
J. Bowden, G. Davey Smith, S. Burgess, Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int. J. Epidemiol. 44, 512–525 (2015)
M. Verbanck, C.-Y. Chen, B. Neale et al. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat. Genet. 50, 693–698 (2018)
Y. Li, D. Huang, B. Wang et al. Socioeconomic factors are associated with the prognosis of Thyroid Cancer. J. Cancer 12, 2507–2512 (2021)
A. Bonner, B. Herring, R. Wang et al. The association of socioeconomic factors and well-differentiated thyroid cancer. J. Surg. Res. 283, 973–981 (2023)
J.B. Shank, C. Are, C.D. Wenos, Thyroid cancer: global burden and trends. Indian J. Surg. Oncol. 13, 40–45 (2022)
J. Jang, D.-S. Yoo, B.C. Chun, Spatial distribution and determinants of thyroid cancer incidence from 1999 to 2013 in Korea. Sci. Rep. 11, 22474 (2021)
L.M. Roche, X. Niu, K.S. Pawlish et al. Thyroid cancer incidence in New Jersey: time trend, birth cohort and socioeconomic status analysis (1979–2006). J. Environ. Public Health 2011, 850105 (2011)
A.M. Roche, S.A. Fedewa, A.Y. Chen, Association of socioeconomic status and race/ethnicity with treatment and survival in patients with medullary thyroid cancer. JAMA Otolaryngol. Head Neck Surg. 142, 763–771 (2016)
M.M. Fidler, S. Gupta, I. Soerjomataram et al. Cancer incidence and mortality among young adults aged 20-39 years worldwide in 2012: a population-based study. Lancet Oncol. 18, 1579–1589 (2017)
A.A. Almubarak, Y.A. Albkiry, A.A. Alsalem et al. The association of low socioeconomic status with advanced stage thyroid cancer. J. Taibah Univ. Med Sci. 16, 482–490 (2021)
S. Siu, J.T. McDonald, M. Rajaraman et al. Is lower socioeconomic status associated with more advanced thyroid cancer stage at presentation? A study in two Canadian centers. Thyroid 24, 545–551 (2014)
B.L. Sprague, S. Warren Andersen, A. Trentham-Dietz, Thyroid cancer incidence and socioeconomic indicators of health care access. Cancer Causes Control 19, 585–593 (2008)
D.-T. Yin, H. He, K. Yu et al. The association between thyroid cancer and insulin resistance, metabolic syndrome and its components: a systematic review and meta-analysis. Int. J. Surg. 57, 66–75 (2018)
L. Yengo, J. Sidorenko, K.E. Kemper et al. Meta-analysis of genome-wide association studies for height and body mass index in ∼700,000 individuals of European ancestry. Hum. Mol. Genet. 27, 3641–3649 (2018)
M. Liu, Y. Jiang, R. Wedow et al. Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use. Nat. Genet. 51, 237–244 (2019)
Funding
This study is supported by the nursing research project of Zhongshan Hospital affiliated from Xiamen University (2023zsyyhlky-002).
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Conceptualization, S.Y. and H.Z.; Data curation, S.Y. and H.Z.; Formal analysis, S.Y. and H.Z.; Visualization, J.L., L.P., H.H. and D.D.; Writing—original draft, S.Y. and H.Z.; Writing—review and editing, H.Z., J.L., H.H., S.Y., L.P., D.D. and N.T.; Supervision, L.J. All authors reviewed the manuscript.
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Fan, S., Jiang, H., Shen, J. et al. Association between educational attainment and thyroid cancer: evidence from a univariable and multivariable Mendelian randomization study. Endocrine (2024). https://doi.org/10.1007/s12020-024-03796-2
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DOI: https://doi.org/10.1007/s12020-024-03796-2