Dermatology: Practical and Conceptual Original Article | Dermatol Pract Concept. 2025;15(3):5264 1 Impact of Rosacea on Keratinocyte Skin Cancers: A Prospective Case-Control Study of Basal and Squamous Cell Carcinoma Risk Aslı Aksu1, Ayşenur Demir1, Hatice Günay1, Pinar Ozdemir Cetinkaya1, Birgul Ozkesici Kurt1, Hazel Ezgi Kaya1, İlknur Kıvanç Altunay1, Deniz Altınel2 1 University of Health Sciences, Şişli Hamidiye Etfal Training and Research Hospital, Department of Dermatology, İstanbul, Turkey 2 University of Health Sciences, Şişli Hamidiye Etfal Training and Research Hospital, Department of Pathology, İstanbul, Turkey Key words: Rosacea And Skin Cancer, Basal Cell Carcinoma, Squamous Cell Carcinoma Risk, Keratinocyte Carcinoma, Dermatological Diseases Citation: Aksu A, Demir A, Günay H, et al. Impact of Rosacea on Keratinocyte Skin Cancers: A Prospective Case-Control Study of Basal and Squamous Cell Carcinoma Risk. Dermatol Pract Concept. 2025;15(3):5264. DOI: https://doi.org/10.5826/dpc.1503a5264 Accepted: May 19, 2025; Published: July 2025 Copyright: ©2025 Aksu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Aslı Aksu, Assoc. Prof, University of Health Sciences, Şişli Hamidiye Etfal Training and Research Hospital, Department of Dermatology, Seyrantepe, Huzur Mah., Cumhuriyet ve Demokrasi Cad., No: 1, Sarıyer, İstanbul, Turkey. ORCID number: 0000-00033979-7486. E-mail: aksuasli@hotmail.com Introduction: The full range of cutaneous comorbidities associated with keratinocyte skin cancers remains to be elucidated. Objectives: We aimed to examine other skin diseases in patients with keratinocyte cancer (KC) and to reveal potential associations between them. Methods: Included in the study were 200 patients with KC and 200 disease-free controls. To identify any additional concomitant dermatological conditions, all study groups underwent examination by two dermatologists. Results: In patients with KC, 87.5% were diagnosed with basal cell carcinoma and 13.5% were diagnosed with squamous cell carcinoma. There was no statistically significant difference between the two groups regarding sunscreen use habits (P =0.284). Patients with KC exhibited a significantly elevated odds ratio (OR) for the presence of rosacea (OR 5.13, 95% CI: 3.2–8.3, P=0.000) and es- pecially erythematotelangiectatic rosacea (ETR) subtype (OR 5.03, 95% CI: 3.1–8.2, P=0.000). An Receiver Operating Characteristic (ROC) curve analysis was conducted to assess the efficacy of ro- sacea in differentiating between the control group and patients with KC. The sensitivity, specificity, negative predictive value, and positive predictive value for rosacea were 45.5%, 86%, 61.2%, and 76.5%, respectively (AUC 0.658, 95% CI: 0.604–0.711, P=0.000), while for ETR it was 44%, 86.5%, ABSTRACT 2 Original Article | Dermatol Pract Concept. 2025;15(3):5264 Introduction Keratinocyte skin cancers represent the most prevalent form of cancer globally. Basal cell carcinoma (BCC) and squa- mous cell carcinoma (SCC) collectively account for 99% of all keratinocyte cancers (KCs) [1]. The prevalence of KCs is higher among the elderly, and as the proportion of the global population aged 60 and above continues to grow, these can- cers are becoming a significant burden on healthcare systems worldwide [2]. A more comprehensive understanding of the etiology of KCs may facilitate more effective treatment and prevention strategies. Predisposing factors include fair skin type, ultraviolet radiation (UVR), immunosuppression, and certain genetic syndromes as well as the human papilloma vi- rus, particularly in the case of SCC. Additionally, exposure to chemicals such as arsenic, chronic ulcers, and burn scars may contribute to the development of these cancers [1]. However, the available data on the relationship between KCs and other cutaneous diseases are limited. In recent years, studies have investigated the relation- ship between KCs and rosacea. However, the results of these studies were inconsistent. Egeberg et al. conducted an epide- miological study to investigate the incidence of cancer in pa- tients with previously diagnosed rosacea compared with the general population [3]. Their 4-year follow-up revealed an increased risk of non-melanoma skin cancer (NMSC), breast cancer, and liver cancer in rosacea patients. In a systematic analysis of the association between rosacea and cancer in US women, Li et al. found that patients with a history of rosacea exhibited an elevated risk of thyroid cancer and BCC [4]. However, Dupont et al. identified no significant correlation between rosacea and the occurrence of skin cancers [5]. Fur- thermore, Lin et al. proposed that a history of rosacea may act as a protective factor against the development of facial BCC [6]. Objectives In light of the inconclusive nature of these findings, our ob- jective was to examine the presence of cutaneous comor- bidities in patients with KC and ascertain whether they are associated. Methods Participants and Protocol This prospective case-control study was conducted in a sin- gle center from September 2023 to May 2024, at the De- partment of Dermatology. The study was approved by the Institutional Ethics Committee (approval number: 4493). All aspects of the study were conducted in accordance with the latest version of the Helsinki Declaration and the Guidelines for Good Clinical Practice. The study population comprised the KCs group, which was recruited from patients admitted to the dermatology outpatient clinic. The control group consisted of age- and sex-matched volunteers consisting of patients’ relatives. The diagnosis of the KC in patients was made based on clinicopathological criteria. The following details were re- corded: the histological type of BCC, the site of localization, the number of lesions, the patient’s skin type, their family history, and their habits concerning using sunscreen. Both the patient group with KC and the control group underwent ex- amination by two dermatologists to identify any additional concomitant dermatological conditions. The study included participants aged 18 years and above. Participants with a syndrome known to cause KC, a history of organ transplan- tation, a confirmed HIV diagnosis, a history of arsenic and chemical exposure, users of photosensitizing drugs, patients with a history of phototherapy, and patients receiving immu- nosuppressive therapy were excluded from the study. Statistical Analysis The statistical analyses were conducted using the SPSS 28.0 software. Descriptive statistics were performed on the data using mean, standard deviation, median, minimum, max- imum, frequency, and ratio values. The distribution of the variables was evaluated using the Kolmogorov-Smirnov and Shapiro-Wilk tests. The Mann-Whitney U test was em- ployed to analyze quantitative independent data exhibiting a non-normal distribution. The chi-squared test was employed to analyze qualitative independent data, while the Fischer test was utilized in instances where the conditions for the chi- squared test were not met. The effect level and cutoff value were subjected to analysis via the ROC curve. The effect level 60.7%, and 76.5%, respectively (AUC 0.653, 95% CI: 0.599–0.706, P=0.000). The presence of rosa- cea demonstrated a significant efficacy in differentiating patients with KC from the control group in all localizations (P< 0.05). Conclusion: The risk of rosacea in patients with KC, particularly those with the ETR subtype, was found to be significantly elevated, irrespective of age, sex, or localization. Original Article | Dermatol Pract Concept. 2025;15(3):5264 3 was analyzed using univariate and multivariate logistic re- gression. Statistically significant was defined as P<0.05. Results A total of 200 patients and 200 controls were included in the study. There were no significant differences between cases and controls regarding age, sex, skin type, or race/ethnicity (all P>0.05). In patients with KC, 175 patients (87.5%) were diagnosed with BCC and 27 patients (13.5%) were diag- nosed with SCC. Subtype analysis revealed that 132 (66.0%) of patients with BCC had nodular BCC, 34 (17.0%) had infiltrative BCC, 19 (9.5%) had superficial BCC, five (2.5%) had adenoid BCC, one (0.5%) had morpheaform BCC, one (0.5%) had pigmented BCC, and four (2.0%) had ba- sosquamous carcinoma. Eighteen of these patients (9.0%) had multiple BCC with different histological types. Three (1.5%) patients also had both BCC and SCC. The majority of KCs were localized on the face (n=153, 76.5%), followed by the trunk (n=22, 11.0%), scalp (n=15, 7.5%), ear (n=6, 3.0%), neck (n=6, 3.0%), lower extremity (n=6, 3.0%), and upper extremity (n=5, 2.5%). The majority of the pa- tients presented with a single lesion (n=165, 82.5%), while 23 (11.5%) had two lesions, 10 (5.0%) had three lesions, one (0.5%) had four lesions, and one (0.5%) had five le- sions. While 188 (94.0%) of the patients had no family history, 12 (6.0%) of the patients had a family history of KC. There was no statistically significant difference between the two groups regarding sunscreen use habits (P=0.284) (Table 1). Table 2 illustrates the prevalence of other dermatological condi- tions observed in patients with KC and control subjects. In comparison to the control group, those with KC were more likely to have rosacea (54.5% vs 14%, P=0.000), dysplastic nevi (2.5% vs 0%, P=0.024), and Bowen’s disease (2.5% vs 0%, P=0.024). Patients with KC exhibited a significantly el- evated odds ratio for the presence of rosacea (OR 5.13, 95% CI: 3.2–8.3, P=0.000) and erythematotelangiectatic rosacea (ETR) (OR 5.03, 95% CI: 3.1–8.2, P=0.000) (Table 2). In the control group, solar lentigo, xerosis cutis, dermal nevi, and lichen simplex chronicus were significantly higher (P=0.013, P=0.000, P=0.043, and P=0.044, respectively). A ROC curve analysis was conducted to assess the efficacy of rosacea in differentiating between the control group and patients with KC. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) for rosacea were 45.5%, 86%, 61.2%, and 76.5%, respectively (AUC 0.658, 95% CI: 0.604–0.711, P=0.000), while for ETR it was 44%, 86.5%, 60.7%, and 76.5%, respectively (AUC 0.653, 95% CI: 0.599–0.706, P=0.000) (Figure 1). The effectiveness of the presence of rosacea in terms of age, sex, family history, skin type, tumor type, and localization in differentiating patients with KC from the control group was examined. The results demonstrated a significant efficacy of rosacea in differentiating patients with KC from the control group in both patients under and those over 65 years of age (OR 4.5, 95% CI: 2.1–9.6, P=0.000 and OR 5.5, 95% CI: 2.9–10.4, P=0.000, respectively). Significant efficacy of ro- sacea in differentiating between KC patients and the control group was observed in both females and males (OR 4.67, 95% CI: 2.4–9.1, P=0.000 and OR 5.99 95% CI: 2.9–12.4, P=0.000, respectively). In the group with a family history, the presence of rosacea was found to be significantly effec- tive in differentiating between the KC and control groups (OR 12.29, 95% CI: 3.5–43.5, P=0.000). In the group with skin types II and III, the presence of rosacea was found to be significantly effective in differentiating between patients with KC and the control group (OR 5.72, 95% CI: 2.9–11.1, P=0.000 and OR 5.27, 95% CI: 2.0–13.7, P=0.001, respec- tively). The presence of rosacea in BCC, nodular BCC, in- filtrative BCC, adenoid BCC, and SCC, as determined by histopathological type, demonstrated a significant efficacy in differentiating between patients with cancer patients and the control group (OR 4.8, 95% CI: 2.9–7.9, P=0.000; OR 4.67, 95% CI: 2.8–7.9, P=0.000; OR 6.14, 95% CI: 2.8–13.4, P=0.000; OR 24.57, 95% CI: 2.6–58, P=0.005; OR 10.44, 95% CI: 4.3–25.1, P=0.000, respectively). The presence of rosacea demonstrated a significant efficacy in differentiating between patients with KC and the control group in all local- izations (P<0.05) (Figure 2). Discussion The present study revealed a robust positive association between KCs and rosacea. It is established that UVR rep- resents a significant risk factor for the development of skin cancers. Furthermore, there is compelling evidence to suggest that UVR plays an important role in the pathogenesis of ro- sacea, with the production of reactive oxygen species and the expression of cathelicidin (in particular, LL-37) being of particular importance [7]. LL-37 may modulate the pro- inflammatory effects of UVR, thereby contributing to in- creased sensitization to sun exposure in rosacea patients [8]. It is hypothesized that patients with rosacea have an altered skin barrier and are more susceptible to higher levels of UV exposure at an early age, which may increase their risk of developing skin cancers such as SCC and BCC [3,4,9]. Chronic sunlight exposure has been demonstrated to impair the capacity of cells to repair damage to their DNA. Patients with KC have been shown to exhibit a decreased capacity for DNA repair. Pathogen-associated molecular patterns (PAMPs) derived from Bacillus oleronius or Demodex mites have been proposed to contribute to the pathogenesis of 4 Original Article | Dermatol Pract Concept. 2025;15(3):5264 Table 1. Demographic and Clinical Characteristics of the Study Groups. KCs   Controls P (n=200)   (n=200) Age (years) mean±SD (med) 68.2 ± 13.3 (70.0)   65.5 ± 14.2 (67.0) 0.059 m Age (years) (n/%) ≤ 50 24   12.0%     27   13.5%   0.419 X² 51-65 56 28.0% 66 33.0% 66-96 120   60.0%     107   53.5%   Sex (n/%) Female 87   43.5%     106   53.0%   0.057 X² Male 113   56.5%     94   47.0%   Skin type (n/%) II 94   47.0%     79   39.5%   0.098 X² III 87 43.5% 89 44.5% IV 19   9.5%     32   16%   Sunscreen use (n/%) (-) 194   97.0%     198   99.0%   0.284 X² (+) 6   3.0%     2   1.0%   Family history (n/%) (-) (+) 188 12 94.0% 6.0% Type of KCs (n/%) BCC 175 87.5% Nodular BCC 132 66.0% Infiltrative BCC 34 17.0% Morpheaform BCC 1 0.5% Superficial BCC 19 9.5% Adenoid BCC 5 2.5% Pigmented BCC 1 0.5% Basosquamous 4 2.0% SCC 27 13.5% Localization (n/%) Scalp 15 7.5% Face 153 76.5% Ear 6 3.0% Neck 6 3.0% Trunk 22 11.0% Upper extremity 5 2.5% Lower extremity 6 3.0% Number of KCs (n/%) I 165 82.5% II 23 11.5% III 10 5.0% IV 1 0.5% V 1 0.5% m Mann-Whitney U test / X² Chi-squared test (Fischer test). Abbreviation: KC: Keratinocyte cancer, SD: Standard deviation rosacea [7,10]. These biological triggers are known to acti- vate Toll-like receptors (TLRs), including TLR-2. TLR stim- ulation results in the activation of the nuclear factor kappa B (NF-κB) pathway, which in turn leads to the production of cytokines, chemokines, and antimicrobial peptides [11]. The Janus kinase/signal transducers and activators of tran- scription (JAK/STAT) pathway plays a role in the LL-37- mediated inflammatory mechanism of rosacea [12]. In a recent study, Deng and colleagues reported that the mecha- nistic target of rapamycin complex 1 (mTORC1) pathway is Original Article | Dermatol Pract Concept. 2025;15(3):5264 5 Table 2. Cutaneous Comorbidities Accompanying the KC and Control Groups and their Comparison. Controls KCs P*N (%) N (%) OR (95% CI) Rosacea 28 (14.0) 91 (54.5) 5.13 (3.2-8.3) 0.000 Erythematotelangiectatic rosacea 27 (13.5) 88 (44) 5.03 (3.1-8.2) 0.000 Papulopustular rosacea 0 (0.0) 3 (1.5) - 0.248 Phymatous rosacea 1 (0.5) 4 (2.0) 4.06 (0.5-36.7) 0.177 Seborrheic keratosis 62 (31.0) 79 (39.5) 1.45 (1.0-2.2) 0.075 Cherry angioma 42 (21.0) 32 (16.0) 0.72 (0.4-1.2) 0.198 Actinic keratosis 24 (12.0) 33 (16.5) 1.45 (0.8-2.6) 0.198 Solar lentigo 28 (14.0) 13 (6.5) 0.43 (0.2-0.9) 0.013 Skin tag 20 (10.0) 15 (7.5) 0.73 (0.4-1.5) 0.376 Xerosis cutis 22 (11.0) 4 (2.0) 0.17 (0.1-0.5) 0.000 Dermal nevi 18 (9.0) 8 (4.0) 0.42 (0.2-1.0) 0.043 Dermatofibroma 8 (4.0) 7 (3.5) 0.87 (0.3-2.5) 0.792 Seborrheic dermatitis 4 (2.0) 5 (2.5) 1.26 (0.3-4.8) 0.736 Verruca vulgaris 3 (1.5) 5 (2.5) 1.68 (0.4-7.1) 0.425 Psoriasis vulgaris 5 (2.5) 3 (1.5) 0.59 (0.1-2.5) 0.475 Stasis dermatitis 5 (2.5) 2 (1.0) 0.39 (0.1-2.1) 0.253 Tinea unguium 5 (2.5) 2 (1.0) 0.39 (0.1-2.1) 0.253 Sebaceous hyperplasia 3 (1.5) 3 (1.5) 1.0 (0.2-5.0) 1,000 Dysplastic nevi 0 (0.0) 5 (2.5) - 0.024 Bowen disease 0 (0.0) 5 (2.5) - 0.024 Lichen simplex chronicus 4 (2.0) 0 (0.0) - 0.044 Acne vulgaris 2 (1.0) 1 (0.5) 0.50 (0.1-5.5) 1,000 Urticaria 1 (0.5) 2 (1.0) 2.01 (0.2-22,4) 1,000 Vitiligo 2 (1.0) 1 (0.5) 0.50 (0.1-5.5) 1,000 Post-inflammatory hyperpigmentation 2 (1.0) 1 (0.5) 0.50 (0.1-5.5) 1,000 Keratoacanthoma 0 (0.0) 3 (1.5) - 0.248 Xanthelasma 0 (0.0) 2 (1.0) - 0.499 Pityriasis versicolor 2 (1.0) 0 (0.0) - 0.499 Tinea pedis 2 (1.0) 0 (0.0) - 0.499 Callus 1 (0.5) 1 (0.5) 1 (0.1-16.1) 1,000 Lichen sclerosus 0 (0.0) 1 (0.5) - 1,000 Melasma 0 (0.0) 1 (0.5) - 1,000 Melanoma 0 (0.0) 1 (0.5) - 1,000 Diabetic foot infection 1 (0.5) 0 (0.0) - 1,000 Decubitus ulcer 1 (0.5) 0 (0.0) - 1,000 Epidermal cysts 0 (0.0) 1 (0.5) - 1,000 Angiokeratoma 0 (0.0) 1 (0.5) - 1,000 Hidradenitis suppurativa 0 (0.0) 1 (0.5) - 1,000 Milia 0 (0.0) 1 (0.5) - 1,000 Nevus spilus 0 (0.0) 1 (0.5) - 1,000 Recurrent aphthous stomatitis 0 (0.0) 1 (0.5) - 1,000 Pemphigus vulgaris 0 (0.0) 1 (0.5) - 1,000 Granuloma annulare 0 (0.0) 1 (0.5) - 1,000 Frontal fibrosing alopecia 0 (0.0) 1 (0.5) - 1,000 Syringoma 1 (0.5) 0 (0.0) - 1,000 Prurigo nodularis 1 (0.5) 0 (0.0) - 1,000 Herpes zoster 1 (0.5) 0 (0.0) - 1,000 * Chi-squared test (Fischer test). Abbreviation: KC: Keratinocyte cancer. 6 Original Article | Dermatol Pract Concept. 2025;15(3):5264 Figure 1 . ROC curve of rosacea and ETR for predicting KCs. (AUC Area under curve; NPV, negative predictive value; PPV, positive predictive value; ROC: receiver operating characteristic; ETR: erythematotelangiectatic rosacea; KC: keratinocyte cancer Figure 2 . Forest plot for the effect of the presence of rosacea on keratinocyte cancers in terms of age, sex, family history, skin type, cancer subtype, and localization. hyperactivated in rosacea [13]. mTOR is a key regulator of several fundamental cellular processes, including cell growth, proliferation, differentiation, survival, autophagy, and mo- tility as well as angiogenesis and lymphangiogenesis. The authors observed a positive correlation between epidermal activation of the mTORC1 pathway and the severity of the rosacea, thereby identifying a mechanism linking the dysreg- ulation of the innate immune system and the inflammatory response in the disease. A substantial body of evidence indicates that the PI3K/ AKT/mTOR/S6K1 pathway can be activated by UVR ex- posure in the development of skin cancers [14,15]. Hy- peractivation of the PI3K/AKT/mTOR axis was identified in both SCC and BCC skin tissues, indicating a potential involvement in the pathogenesis and malignant progres- sion of these tumors [16,17]. Furthermore, the activation of the STAT3 and NF-κB pathways is also a significant factor in the development of KC [18]. The expression of Vascular Endothelial Growth Factor (VEGF), a crucial regulator of angiogenesis and tumor growth, is elevated in both rosacea and KCs. The observation that these two diseases share common pathogenic mechanisms may be associated with the increased prevalence of KC in patients with rosacea. Original Article | Dermatol Pract Concept. 2025;15(3):5264 7 was observed for nodular, infiltrative, and adenoid BCCs. Conversely, no significant risk was identified for superficial BCCs and basosquamous carcinomas. Morpheaform and pigmented BCC were observed in a single patient. The find- ings of our study indicate that the presence of rosacea is an independent risk factor for KCs, irrespective of age and sex, and in patients with skin types II and III. Regarding other cutaneous comorbidities, the prevalence of dysplastic nevus and Bowen’s disease was significantly higher in the group of patients with KC compared to the control group. However, the number of cases was limited to five patients in the KC group, with no case observed in the control group. In a cohort of 11,420 patients with rosacea, Cho et al. reported an increased risk of actinic keratosis and KC [22]. The present study did not find an increased risk of actinic keratosis. Limitations The study’s key strengths are its prospective case-control design and its ability to compare tumor localization and subtype. However, it has several limitations. First, it was con- ducted at a single center, which may have introduced some bias. Second, due to the demographic characteristics of our region, there was no patient with Fitzpatrick skin type I. Conclusion This prospective case-control study investigated cutaneous comorbidities in patients with KC in detail. The risk of ro- sacea in patients with KC, particularly those with the ETR subtype, was found to be significantly elevated, irrespective of age, sex, or localization. We recommend that individuals with rosacea undergo regular examinations for the develop- ment of KC and that patients be made aware of the impor- tance of sun protection. Ethics Approval: The clinical study was approved by the Uni- versity of Health Sciences, Şişli Hamidiye Etfal Training and Research Hospital local ethics committee (Approval num- ber: 4493), and was performed in accordance with the ethi- cal standards of the Declaration of Helsinki. Informed Consent: Informed consent was obtained from all patients and control participants included in the study. References 1. Fahradyan A, Howell AC, Wolfswinkel EM, Tsuha M, Sheth P, Wong AK. Updates on the management of Non-Melanoma Skin Cancer (NMSC). Healthcare (Basel). 2017;5(4):82. DOI: 10.3390/healthcare5040082. PMID: 29104226 In our study, the sensitivity, specificity, NPV, and PPV of the effectiveness of the presence of rosacea in differentiat- ing between patients with KC and the control group were 45.5%, 86.0%, 61.2%, and 76.5%, respectively. For ETR, the corresponding values were 44.0%, 86.5%, 60.7%, and 76.5%. Recent studies have indicated that there is an asso- ciation between rosacea and numerous comorbidities, in- cluding hypertension, autoimmune disease, cardiovascular disease, gastrointestinal disorders, dyslipidemia, and psychi- atric disorders [19,20]. Furthermore, numerous studies have investigated the potential link between rosacea and various forms of cancer. In a two-sample bidirectional Mendelian randomization study, Luo et al. identified a positive associ- ation between rosacea and glioma, NMSC, and breast can- cer [21]. In a cohort study by Egeberg et al. analyzing data from nationwide Danish registries, a statistically significant association was observed between rosacea and NMSC [3]. Patients with rosacea were more likely to develop NMSC compared to patients in the reference population (HR 1.36, 95% CI: 1.26–1.47). In another study, Cho et al. con- ducted a nationwide, population-based retrospective cohort study of 11,420 patients in South Korea [22]. The results demonstrated a notable correlation between rosacea and NMSC incidence in comparison to the reference population (HR 2.66, 95% CI: 1.53–4.61). In contrast, in the study by Lin et al., 2453 of the 4537 patients diagnosed with BCC had facial BCC, and 267 of them had a history of rosacea [6]. The results of the study demonstrated that the prevalence of facial BCC in patients with a history of rosacea was mark- edly lower than in patients without rosacea (3.80 vs 5.07 per 100 patients; P< 0.001). A comparison of BCC of the body revealed no significant difference between patients with and without a history of rosacea. Lazzeri et al. presented a case series and a literature review of a total of 46 patients with rhinophyma who subsequently developed skin cancer [23]. Of the patients in question, 28 were diagnosed with BCC, 11 with SCC, four with both SCC and BCC, and one with angiosarcoma. With regard to SCC, 577 cases of SCC were identified in a population of 90,238 women in the USA [24]. The results demonstrated a significant association between rosacea and SCC (RR 1.40. 95% CI: 1.02–1.93). In this study, the location of SCC was also divided into two groups: head and neck and non-head and neck. These groups were then compared in terms of the history of rosacea. The re- sults demonstrated a significant association between rosacea and head and neck SCC (RR 1.71, 95% CI: 1.09–2.69). The findings of our study indicate that the presence of rosacea is associated with an increased risk of KC in all localizations. Furthermore, the majority of patients with rosacea were observed to belong to the ETR subgroup. Concerning the risk of BCC subgroups, a significant and positive association 8 Original Article | Dermatol Pract Concept. 2025;15(3):5264 14. Leo MS, Sivamani RK. Phytochemical modulation of the Akt/ mTOR pathway and its potential use in cutaneous disease. Arch Dermatol Res. 2014;306:861-871. DOI: 10.1007/s00403-014- 1480-8. PMID: 24972910 15. Chamcheu JC, Roy T, Uddin MB, et al. Role and therapeutic targeting of the PI3K/Akt/mTOR signaling pathway in skin cancer: A review of current status and future trends on natural and synthetic agents therapy. Cells. 2019;8:803. DOI: 10.3390 /cells8080803. PMID: 31370278 16. Einspahr JG, Calvert V, Alberts DS, et al. Functional protein pathway activation mapping of the progression of normal skin to squamous cell carcinoma. 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