[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-340612-105":3,"detail-sidebar-cat-0-en-105":85,"doc-detail-340612-en":134},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":78,"head_meta":80,"extra_data":82,"updated_unix":84},105,"en","single-nucleotide-polymorphisms-on-toll-like-receptor-4-and-the-risk-of-developing-skin-cancer","Single Nucleotide Polymorphisms on Toll-like Receptor-4 and the Risk of Developing Skin Cancer","","Exposure to solar ultraviolet (UV) radiation is an established risk factor for skin cancer. Toll-like receptor-4 (TLR4)-mediated immune dysregulation has emerged as a key mechanism behind harmful effects of acute and chronic UV exposure and skin cancer in mice. The objective was to test associations between TLR4 single nucleotide polymorphisms (SNPs) and the risk of developing keratinocyte carcinomas. Skin cancer patients and controls completed surveys; DNA genotyping and descriptive analytics were followed by multivariable logistic regression. In a cohort of 93 patients and 94 controls, D299G/T399I showed no statistically significant association (OR=0.34; 95% CI 0.11-1.07; p=0.065). Some protective effect was suggested but requires validation in larger cohorts.",{"@graph":14,"@context":77},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/single-nucleotide-polymorphisms-on-toll-like-receptor-4-and-the-risk-of-developing-skin-cancer/340612/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/single-nucleotide-polymorphisms-on-toll-like-receptor-4-and-the-risk-of-developing-skin-cancer/340612.png","ImageObject",300,407,{"name":42,"@type":43},"Genevieve","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-30","2026-09-22",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69,73],{"name":60,"@type":61,"acceptedAnswer":62},"What is the study aiming to determine about TLR4?","Question",{"text":63,"@type":64},"The study tests whether TLR4 single nucleotide polymorphisms are associated with the risk of developing keratinocyte carcinomas.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How were participants and samples collected for the analysis?",{"text":68,"@type":64},"Skin cancer patients and controls completed a cross-sectional survey on personal and family history and sunscreen use. Peripheral blood samples were collected, DNA was extracted, and TLR4 SNPs were genotyped.",{"name":70,"@type":61,"acceptedAnswer":71},"Did the D299G/T399I SNP show a significant association with skin cancer risk?",{"text":72,"@type":64},"No. The study found no statistically significant association between D299G/T399I and skin cancer after adjusting for multiple covariates (OR=0.34; 95% CI 0.11-1.07; p=0.065).",{"name":74,"@type":61,"acceptedAnswer":75},"What conclusion did the authors draw and what is needed next?",{"text":76,"@type":64},"The findings suggested a possible protective effect of the TLR4 SNPs, but it was not statistically significant. Validation in a larger cohort is warranted.","https://schema.org",{"og:url":32,"og:type":79,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":81,"canonical":32},"index,follow",{"doc_id":83,"site_id":7},340612,1790111992,{"code":4,"msg":86,"data":87},"success",[88,92,96,100,105,110,114,119,123,126,130],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},"Exam",70,"exam",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},5,"Comic",60,"comic",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":107,"show_sort_weight":108,"slug":109},6,"Technology",50,"technology",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},7,40,"healthcare",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},8,"Research & Report",30,"research-report",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":121,"slug":122},"Religion & Spirituality",20,"religion-spirituality",{"id":121,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":121,"slug":125},"World Cup","world-cup",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":127,"slug":129},10,"Lifestyle","lifestyle",{"id":131,"doc_module":4,"doc_module_name":25,"category_name":132,"show_sort_weight":101,"slug":133},19,"General","general",{"code":4,"msg":86,"data":135},{"doc_id":83,"user_id":136,"nickname":42,"user_avatar":137,"doc_module":4,"category_id":111,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":138,"file_id":139,"file_url":140,"file_type":141,"file_size":142,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":115,"language":143,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":144,"faqs":145,"seo_title":146,"seo_description":12,"update_tm":147,"read_time":121},1374391974585,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Communication  \nSingle Nucleotide Polymorphisms on Toll-like Receptor-4 and the Risk of Developing Skin Cancer  \nNabiha Yusuf 1, *, Noha Sharafeldin 2, Mohammad Saleem 1, Tom Callens 3, Ludwine M. Messiaen 3 and Craig A. Elmets 1  \nCitation: Yusuf, N.; Sharafeldin, N.; Saleem, M.; Callens, T.; Messiaen, L.M.; Elmets, C.A. Single Nucleotide Polymorphisms on Toll-like Receptor-4 and the Risk of Developing Skin Cancer. Int. J. Mol.  \nSci. 2024, 25, 12728. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms252312728](10.3390/ijms252312728)  \nAcademic Editor: Silvia Cantara  \nReceived: 30 October 2024  \nRevised: 18 November 2024  \nAccepted: 22 November 2024  \nPublished: 27 November 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Dermatology, University of Alabama at Birmingham, 1670 University Boulevard VH566A, Birmingham, AL 35294, USA  \n2 Department of Hematology and Oncology, UAB Heersink School of Medicine, Birmingham, AL 35233, USA  \n3 Medical Genomics Laboratory, Department of Clinical and Diagnostic Sciences, UAB School of Health Professions, Birmingham, AL 35233, USA  \n* [Correspondence: nabihayusuf@uabmc.edu](Correspondence: nabihayusuf@uabmc.edu)  \nAbstract: Exposure to solar ultraviolet (UV) radiation is an established risk factor for skin cancer. Toll-like receptor-4 (TLR4)-mediated immune dysregulation has emerged as a key mechanism for the detrimental effects of acute and chronic UV exposure and skin cancer in mice. Single nucleotide polymorphisms (SNPs) on the TLR4 gene have been reported to increase or decrease susceptibility to various cancers in other organs. There is limited information on TLR4 SNPs and susceptibility to human keratinocyte carcinomas. The study’s objective is to test the association between TLR4 SNPs and the risk of developing keratinocyte carcinomas. Skin cancer patients and controls at the University of Alabama at Birmingham completed a cross-sectional survey on personal and family history of skin cancer as well as on sunscreen use and tanning proneness. Peripheral blood samples were obtained from participants, and DNA was extracted to genotype the TLR4 SNPs. Descriptive analytics were used to describe the cohort. Multivariable logistic regression models were used to assess the association between TLR4 SNPs and skin cancer risk. The sample consisted of a cohort of 93 skin cancer patients over the age of 50 and 94 controls; 33.3% of cases and 44.7% of controls were females; 12 .9% of cases and 17% of controls had a TLR4 SNP. The most common SNP was D299G/T399I in 9.7% of skin cancer patients and 13.8% of controls. We did not find a statistically significant association between the D299G/T399I SNP and skin cancer (odds ratio (OR) = 0.34, 95% CI: 0.11, 1.07, p = 0.065) adjusting for age, sex, eye color, actinic keratosis, sunscreen use and reapplication, and family history of skin cancer. Based on our findings from our limited cohort of participants, we found some protective effect for the TLR4 SNP for skin cancer, which was not statistically significant. Validation of these findings in a larger cohort is warranted.  \nKeywords: toll-like receptor-4; single nucleotide polymorphisms; skin cancer  \n1. Introduction  \nNon-melanoma skin cancer (NMSC) is the most commonly diagnosed cancer in the United States (US) . An estimated 1.8 million cases of squamous cell carcinoma (SCC) and 3.6 million cases of basal cell carcinoma (BCC) are diagnosed in the US each year [1], and $4.8 billion is expended on the management of NMSC cases [2] . NMSC cases also account for more than 5400 deaths every month worldwide [3] . Risk factors for NMSC include exposure to ultra","cbCairiHSZiOzYrS","https://ap.wps.com/l/cbCairiHSZiOzYrS","pdf",856751,"English","# Abstract\n# Introduction\n## Non-melanoma skin cancer and risk factors\n## Role of TLR4 in immune activation and cancer progression","[{\"question\":\"What is the study aiming to determine about TLR4?\",\"answer\":\"The study tests whether TLR4 single nucleotide polymorphisms are associated with the risk of developing keratinocyte carcinomas.\"},{\"question\":\"How were participants and samples collected for the analysis?\",\"answer\":\"Skin cancer patients and controls completed a cross-sectional survey on personal and family history and sunscreen use. Peripheral blood samples were collected, DNA was extracted, and TLR4 SNPs were genotyped.\"},{\"question\":\"Did the D299G/T399I SNP show a significant association with skin cancer risk?\",\"answer\":\"No. The study found no statistically significant association between D299G/T399I and skin cancer after adjusting for multiple covariates (OR=0.34; 95% CI 0.11-1.07; p=0.065).\"},{\"question\":\"What conclusion did the authors draw and what is needed next?\",\"answer\":\"The findings suggested a possible protective effect of the TLR4 SNPs, but it was not statistically significant. Validation in a larger cohort is warranted.\"}]","Single Nucleotide Polymorphisms on Toll-like Receptor-4 and the Risk of Developing Skin Cancer | PDF",1790037690]