Thyroid dysfunction and risk of cutaneous malignant melanoma: a bidirectional two-sample Mendelian randomization study

BackgroundEpidemiologic and observational data have found a risk association between thyroid dysfunction and cutaneous malignant melanoma (CMM), however, the cause and direction of these effects are yet unknown. By using a bidirectional two-sample Mendelian randomization (MR) methodology, we hoped to further investigate the causal link between thyroid dysfunction and CMM in this work.MethodsA genome-wide association study (GWAS) of 9,851,867 single nucleotide polymorphisms (SNPs) in a European population was used to develop genetic tools for thyroid dysfunction. Hypothyroidism was linked to 22,687 cases and 440,246 controls. For hyperthyroidism, there were 3545 cases and 459,388 controls. A total of 3751 cases and 372016 controls were included in the genetic data for CMM from UK Biobank (http://www.nealelab.is/uk-biobank) (the Dataset: ieu - b - 4969). Among them, inverse variance weighting (IVW) is the main MR Analysis method for causality assessment. MR-Egger method, MR Pleiotropic residual and outlier test (MR-PRESSO), and simple and weighted median (VM) were used to supplement the IVW method. Sensitivity analyses, mainly Cochran’s Q test, leave-one-out analysis, and MR Egger intercept test were performed to assess the robustness of the outcomes.ResultsThe two-sample MR Analysis results revealed a negative correlation between genetically predicted hypothyroidism and the probability of CMM (OR=0.987, 95%CI =0.075-0.999, p=0.041). The supplemental MR Analysis did not reveal any statistically significant differences, although the direction of the effect sizes for the other approaches was consistent with the IVW effect sizes. The results of the causal analysis were relatively robust, according to a sensitivity analysis. The risk of CMM was unaffected by hyperthyroidism (p>0.05). No correlation between CMM and thyroid dysfunction was seen in the reverse MR analysis.ConclusionAlthough the magnitude of the causal association is weak and further investigation of the mechanism of this putative causal relationship is required, our findings imply that hypothyroidism may be a protective factor for CMM

Comprehensive pan-carcinoma analysis of ITGB1 distortion and its potential clinical significance for cancer immunity

Abstract The human protein-coding gene ITGB1 (Integrin 1), also known as CD29, has a length of 58048 base pairs. The Integrin family's most prevalent subunit, it participates in the transmission of numerous intracellular signaling pathways. A thorough examination of ITGB1's functions in human malignancies, however, is inadequate and many of their relationships to the onset and development of human cancers remain unknown. In this work, we examined ITGB1's role in 33 human cancers. Finally, a multi-platform analysis revealed that three of the 33 malignancies had significantly altered ITGB1 expression in tumor tissues in comparison to normal tissues. In addition, it was discovered through survival analysis that ITGB1 was a stand-alone prognostic factor in a number of cancers. ITGB1 expression was linked to immune cell infiltration in colon cancer, according to an investigation of immune infiltration in pan-cancer. In the gene co-expression research, ITGB1 showed a positive connection with the majority of the cell proliferation and EMT indicators, indicating that ITGB1 may have an essential function in controlling cancer metastasis and proliferation. Our pan-cancer analysis of ITGB1 gives evidence in favor of a further investigation into its oncogenic function in various cancer types

Expression and prognostic analyses of early growth response proteins (EGRs) in human breast carcinoma based on database analysis

Background Early growth response proteins (EGRs), as a transcriptional regulatory family, are involved in the process of cell growth, differentiation, apoptosis, and even carcinogenesis. However, the role of EGRs in tumors, their expression levels, and their prognostic value remain unclear. Methods Using the Oncomine database, Kaplan–Meier Plotter, bcGenExMiner v4.2, cBioPortal, and other tools, the association between the survival data of breast carcinoma (BC) patients and transcriptional levels of four EGRs was investigated. Results According to the Oncomine database, in comparison to normal tissues, the expression level of EGR2/3 mRNA in BC tissues was decreased, but there was no difference in the expression level of EGR4 mRNA. On the basis of the Scarff-Bloom-Richardson (SBR) grading system, the downregulated expression level of EGR1/2/3 and upregulated expression level of EGR4 were correlated with an increased histological differentiation level, with significant differences (p < 0.05). Kaplan–Meier curves suggest that a reduction in EGR2/3 mRNA expression is related to recurrence-free survival (RFS) in BC patients. In addition, the mRNA expression level of EGR1/2/3 was related to metastatic relapse-free survival (MRFS) in BC patients with metastatic recurrence (p < 0.05). Conclusion EGR1/2/3 can be utilized as an important factor for evaluating prognosis and may be relevant to diagnosis. EGR4 may play a role in the occurrence and development of BC. The specific function and mechanism of EGRs in BC deserve further study

Eliciting national and subnational sets of disability weights in mainland China: Findings from the Chinese disability weight measurement study

Summary: Background: The disability weight (DW) quantifies the severity of health states from disease sequela and is a pivotal parameter for disease burden calculation. We conducted a national and subnational DW measurement in China. Methods: In 2020–2021, we conducted a web-based survey to assess DWs for 206 health states in 31 Chinese provinces targeting health workers via professional networks. We fielded questions of paired comparison (PC) and population health equivalence (PHE). The PC data were analysed by probit regression analysis, and the regression results were anchored by results from the PHE responses on the DW scale between 0 (no loss of health) and 1 (health loss equivalent to death). Findings: We used PC responses from 468,541 respondents to estimate DWs of health states. Eight of 11 domains of health had significantly negative coefficients in the regression of the difference between Chinese and Global Burden of Disease (GBD) DWs, suggesting lower DW values for health states with mention of these domains in their lay description. We noted considerable heterogeneity within domains, however. After applying these Chinese DWs to the 2019 GBD estimates for China, total years lived with disability (YLDs) increased by 14·9% to 177 million despite lower estimates for musculoskeletal disorders, cardiovascular diseases, mental disorders, diabetes and chronic kidney disease. The lower estimates of YLDs for these conditions were more than offset by higher estimates of common, low-severity conditions. Interpretation: The differences between the GBD and Chinese DWs suggest that there might be some contextual factors influencing the valuation of health states. While the reduced estimates for mental disorders, alcohol use disorder, and dementia could hint at a culturally different valuation of these conditions in China, the much greater shifts in YLDs from low-severity conditions more likely reflects methodological difficulty to distinguish between health states that vary a little in absolute DW value but a lot in relative terms. Funding: This work was supported by the National Natural Science Foundation of China [grant number 82173626], the National Key Research and Development Program of China [grant numbers 2018YFC1315302], Wuhan Medical Research Program of Joint Fund of Hubei Health Committee [grant number WJ2019H304], and Ningxia Natural Science Foundation Project [grant number 2020AAC03436]

Eliciting national and subnational sets of disability weights in mainland China: Findings from the Chinese disability weight measurement study

Background: The disability weight (DW) quantifies the severity of health states from disease sequela and is a pivotal parameter for disease burden calculation. We conducted a national and subnational DW measurement in China. Methods: In 2020–2021, we conducted a web-based survey to assess DWs for 206 health states in 31 Chinese provinces targeting health workers via professional networks. We fielded questions of paired comparison (PC) and population health equivalence (PHE). The PC data were analysed by probit regression analysis, and the regression results were anchored by results from the PHE responses on the DW scale between 0 (no loss of health) and 1 (health loss equivalent to death). Findings: We used PC responses from 468,541 respondents to estimate DWs of health states. Eight of 11 domains of health had significantly negative coefficients in the regression of the difference between Chinese and Global Burden of Disease (GBD) DWs, suggesting lower DW values for health states with mention of these domains in their lay description. We noted considerable heterogeneity within domains, however. After applying these Chinese DWs to the 2019 GBD estimates for China, total years lived with disability (YLDs) increased by 14·9% to 177 million despite lower estimates for musculoskeletal disorders, cardiovascular diseases, mental disorders, diabetes and chronic kidney disease. The lower estimates of YLDs for these conditions were more than offset by higher estimates of common, low-severity conditions. Interpretation: The differences between the GBD and Chinese DWs suggest that there might be some contextual factors influencing the valuation of health states. While the reduced estimates for mental disorders, alcohol use disorder, and dementia could hint at a culturally different valuation of these conditions in China, the much greater shifts in YLDs from low-severity conditions more likely reflects methodological difficulty to distinguish between health states that vary a little in absolute DW value but a lot in relative terms. Funding: This work was supported by the National Natural Science Foundation of China [grant number 82173626], the National Key Research and Development Program of China [grant numbers 2018YFC1315302], Wuhan Medical Research Program of Joint Fund of Hubei Health Committee [grant number WJ2019H304], and Ningxia Natural Science Foundation Project [grant number 2020AAC03436]