Correspondence
Aspects related to the inference of causality in cross-sectional studies. Comments on: “8-Hydroxy-2’-deoxyguanosine protein immunoexpression is associated with the pathogenesis of actinic cheilitis”
Ivanka Miranda de Castro Martins, Anna Carolina Miola, Luiz Eduardo Fabrício de Melo Garbers, Hélio Amante Miot
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Department of Infectology, Dermatology, Imaging Diagnosis and Radiotherapy, Faculty of Medicine, Universidade Estadual Paulista, Botucatu, SP, Brazil
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Comments on: “8-Hydroxy-2’-deoxyguanosine protein immunoexpression is associated with the pathogenesis of actinic cheilitis”" "tieneTextoCompleto" => true "saludo" => "<span class="elsevierStyleItalic">Dear Editor,</span>" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "793" "paginaFinal" => "794" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Ivanka Miranda de Castro Martins, Anna Carolina Miola, Luiz Eduardo Fabrício de Melo Garbers, Hélio Amante Miot" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Ivanka Miranda de Castro" "apellidos" => "Martins" ] 1 => array:2 [ "nombre" => "Anna Carolina" "apellidos" => "Miola" ] 2 => array:2 [ "nombre" => "Luiz Eduardo Fabrício de Melo" "apellidos" => "Garbers" ] 3 => array:4 [ "nombre" => "Hélio Amante" "apellidos" => "Miot" "email" => array:1 [ 0 => "helio.a.miot@unesp.br" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Department of Infectology, Dermatology, Imaging Diagnosis and Radiotherapy, Faculty of Medicine, Universidade Estadual Paulista, Botucatu, SP, Brazil" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Due to the potential for malignancy and contiguity to the photoprotected mucosa, actinic cheilitis (AC) represents the archetype of the activity of the cutaneous field cancerization (CFC), an opportune model for research about carcinogenesis in <span class="elsevierStyleItalic">anima nobile</span>.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Therefore, the article by Varela et al., which explored the expression of 8-OHdG in AC, concluding for association with pathogenesis, was read with interest.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The authors should be congratulated; however, some comments related to the generalization of the results are essential.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The search for histopathological markers of CFC activity is relevant for its characterization, understanding of the pathogenesis, and to define outcome in therapeutic prospection. To date, no high-performance markers have been identified; however, the expression of p53, Ki67, detection of cyclobutane-thymidine dimers, and degree of epithelial dysplasia are the most studied ones.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">While ultraviolet radiation induces oxidative stress in the epithelium and topical antioxidants reduce CFC activity, markers of oxidative damage in DNA are candidates for characterizing CFC activity.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> 8-OHdG expression is rapidly increased in sun-exposed epithelium, remaining for days after a radiation dose; however, it can also be induced by other oxidative agents, such as smoking and underlying inflammation.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Human skin is an organ which interacts with the environment and has, during evolution, developed DNA repair, apoptotic, and antioxidant mechanisms. Their failure justifies the higher incidence of neoplasms in syndromes (e.g., xeroderma pigmentosum), immunosuppressed patients, and the elderly. Lower lips are chronically exposed to the sun, justifying the regular expression of markers of oxidative damage. However, this study did not include a control group with healthy, photoexposed lips, nor was the photoprotected mucosa sampled, which would help in the comparative evaluation of 8-OHdG expression patterns.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The lack of association between the 8-OHdG histopathological score and the degree of AC dysplasia or smoking does not corroborate the expectation of a biological gradient. Moreover, the expression of 8-OHdG in AC, although intense, does not allow inferring that it is causally involved in the etiopathogenic process, or that it is a by-product of the epithelium with dysfunctional antioxidant mechanisms.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Finally, the nuclear and cytoplasmic expression of 8-OHdG must be analyzed separately, since damage to mitochondrial DNA induces autophagy, whereas nuclear damage is potentially carcinogenic. Although the authors declared that there was predominantly nuclear expression, but cytoplasmic too, there was no differential analysis, which makes the interpretation of these results difficult.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Therefore, the conclusion about the involvement of 8-OHdG in the pathogenesis of AC should be interpreted with caution.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financial support</span><p id="par0040" class="elsevierStylePara elsevierViewall">None declared.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors' contributions</span><p id="par0045" class="elsevierStylePara elsevierViewall">Ivanka Miranda de Castro Martins: Design and planning of the study, drafting and editing of the manuscript; approval of the final version of the manuscript.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Anna Carolina Miola: Design and planning of the study, drafting and editing of the manuscript; approval of the final version of the manuscript.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Luiz Eduardo Fabrício de Melo Garbers: Design and planning of the study, drafting and editing of the manuscript; approval of the final version of the manuscript.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Hélio Amante Miot: Design and planning of the study, drafting and editing of the manuscript; approval of the final version of the manuscript.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">None declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Financial support" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Authors' contributions" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflicts of interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2024-03-07" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Study conducted at the Department of Infectious Diseases, Dermatology, Imaging Diagnosis and Radiotherapy, Faculty of Medicine, Universidade Estadual Paulista, Botucatu, SP, Brazil.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cutaneous field cancerization: clinical, histopathological and therapeutic aspects" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "L.A. 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