Interaction between Genetic Risks and Socioeconomic Factors on Thyroid Cancer: Evidence from 0.5 Million UK Biobank Participants

SIMPLE SUMMARY: The interaction effect between genetic risk and socioeconomic factors on thyroid cancer remains unclear. In this study, we utilized a large-scale population dataset to comprehensively estimate the independent effects of genetic and socioeconomic factors and their interaction with thyroid cancer (TCa). The results of this study showed that (1) telomerase reverse transcriptase (TERT) variants significantly related to TCa risk were commonly situated in the intron 2 region; and (2) low-to-medium genetic risk combined with low household income was associated with a high TCa risk, whereas medium-to-high genetic risk combined with a higher education level and frequent social connection was associated with an increased TCa risk. These findings furnish insights into risk stratification and are informative for implementing the precise screening of thyroid cancer in the general population. ABSTRACT: Background: There is a research gap between genetic predisposition, socioeconomic factors, and their interactions on thyroid tumorigenesis. Methods: Individual and genetic data were obtained from UK Biobank. Logistic regression models were used to evaluate the association between genetic risk, socioeconomic factors, and thyroid cancer (TCa). A stratified analysis was conducted to estimate their joint effects. A two-sample Mendelian randomization (MR) analysis was further used to examine the potential causality. Results: A total of 502,394 participants were included in this study. Three index loci (rs4449583, rs7726159, and rs7725218) of telomerase reverse transcriptase (TERT) were found to be significantly related to incident TCa. Association analyses showed that high genetic risk, low household income, and high education level were independent risk factors, while unemployment and frequent social connection were suggestive risk factors for TCa. Interaction analyses showed that in participants with low genetic risk, low household income was significantly associated with TCa (odds ratio [OR] = 1.56, 95% confidence interval [CI]: 1.00–2.46). In participants with high genetic risk, those with a high education level (OR = 1.32, 95%CI: 1.06–1.65) and frequent social connection (OR = 1.36, 95%CI: 1.02–1.81) had a significantly increased risk of TCa. However, no causal relationship was observed in the MR analysis. Conclusion: Interactions exist between genetic risk, household income, education level, and social connection and thyroid cancer.