br Conclusion br In conclusion we found
In conclusion, we found that elevated IL-6 levels at baseline were significantly associated with risk of lung cancer; in analyses using repeated measures of IL-6 over time, findings were significant in the previously applied Model 1, but not in Model 2, which accounted for additional covariates. Baseline CRP was associated with increased haz-ard of incidence lung cancer in Model 1, but not in the model adjusting for additional covariates. TNF-α levels were not statistically significantly associated with increased hazard of incident lung cancer in either model. Future prospective studies that plot trajectories of repeated measures of TNF-α, IL-6, and CRP, and leverage larger sample sizes, will provide further insight into the association of chronic Dynasore with the risk of lung cancer.
Ethics Approval and Consent to Participate
All participants in the Dynamics of Health, Aging and Body Composition study gave informed written consent to participate in the study. The protocol for the study was approved by the institutional review boards of the clinical sites in Pittsburgh, PA and Memphis, TN, as well as at the Data Coordinating Center of the University of California, San Francisco. Researchers also obtained expedited IRB approval for secondary data analyses via the University of California, San Francisco.
Consent to Publish
Not applicable. In no part of this manuscript do we include details, im-ages, or videos relating to an individual person.
Availability of Data and Materials
The datasets generated and/or analyzed during the current study are available on request with the completion of a data access proposal from the Dynamics of Health, Aging, and Body Composition research team. (https://healthabc.nia.nih.gov/) To request data, submit analysis plan proposals to the Health ABC Publications Committee Coordinator at the University of California, San Francisco Coordinating Center for approval.
Conflict of Interest Statement
We have read and understood the Elsevier policy on declaration of con-flicts of interests and declare we have no conflicts of interest.
We would like to thank the Health, Aging and Body Composition Study Research Team and the Statistical Coordinating Center at the University of California, San Francisco for their support throughout the project. We would also like to thank all of the participants in the HealthABC study for giving their time.
Concept and Design: Demb, Wei, Izano, Kritchevsky, Swede, Gregorich, Braithwaite.
Analysis and Interpretation of Data: Demb, Wei, Izano, Gregorich, Braithwaite.
Drafting of Manuscript: Demb, Wei, Izano, Braithwaite.
Critical Revision of the Manuscript for Important Intellectual Content: Demb, Wei, Izano, Kritchevsky, Swede, Newman, Shlipak, Akinyemiju, Gregorich, Braithwaite.
Statistical Analysis: Demb, Wei, Gregorich, Braithwaite.
Obtained Funding: Braithwaite.
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Chronic Inflammation Promotes Skin Carcinogenesis in Cancer-Prone Discoid Lupus Erythematosus
Trevor J. Cunningham1, Jean-Pierre Eliane2, Maia Livneh2, Thomas D. Horn1, Ilana S. Rosman3,4, Amy Musiek3, Milan J. Anadkat3 and Shadmehr Demehri1
High-risk skin cancer is a rare, but severe, complication associated with discoid lupus erythematosus (DLE). Chronic scar, inflammation, UVR, and immunosuppressive medications are proposed explanations for this heightened skin cancer risk; however, the exact mechanism driving skin carcinogenesis in DLE is unknown. The distinct co-localization of multiple independent skin cancers with areas of active inflammation in two DLE patients followed over 8 years strongly suggested that lupus inflammation promotes skin carcinogenesis in DLE. To investigate this clinical observation, we subjected lupus-prone MRL/lpr and control (MRL/n) mice to a skin carcinogenesis protocol. Skin tumors developed preferentially within the cutaneous lupus inflammation without scarring in MRL/lpr mice (P < 0.01). The inflammation in MRL/lpr skin was characterized by the accu-mulation of regulatory T cells, mast cells, M2 macrophages, and markedly elevated transforming growth factor-b1 and IL-6 levels, which have been linked to tumor promotion. Tacrolimus treatment reduced skin inflammation and blocked cancer development in MRL/lpr mice (P ¼ 0.0195). A similar tumor-promoting im-mune environment was detected in SCCs and the perilesional skin of cancer-prone DLE patients. Therefore, discoid lupus inflammation promotes skin cancer in high-risk DLE patients, and blocking the inflammation may be critical for preventing this life-threatening complication of DLE.