{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:28:36Z","timestamp":1790126916754,"version":"4.0.1"},"reference-count":85,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008252","name":"University of Udine","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008252","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/05ht0mh31","id-type":"ROR","asserted-by":"publisher"}]},{"name":"European Union\u2014NextGenerationEU, Missione 4 Componente 2","award":["CUP G23C25000630006"],"award-info":[{"award-number":["CUP G23C25000630006"]}]},{"name":"European Union\u2014NextGenerationEU, Missione 4 Componente 2","award":["MSCA2024_0000113"],"award-info":[{"award-number":["MSCA2024_0000113"]}]},{"award":["CUP G23C25000630006"],"award-info":[{"award-number":["CUP G23C25000630006"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]},{"award":["MSCA2024_0000113"],"award-info":[{"award-number":["MSCA2024_0000113"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]},{"name":"P.I. Petris Gianluca","award":["MFAG 2024-ID. 30501"],"award-info":[{"award-number":["MFAG 2024-ID. 30501"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Hypoxia and oxidative stress are central features of cutaneous melanoma biology. Body mass index (BMI) and smoking, both of which can influence systemic hypoxia, inflammation, and oxidative stress, have shown inconsistent associations with melanoma. We investigated the association of the hypoxia-inducible factor-1 alpha gene (HIF1A) rs11549465 (1772 C&gt;T; Pro582Ser) polymorphism, alone and in combination with overweight\/obesity or smoking habits, with cutaneous melanoma susceptibility and clinicopathological characteristics. Methods: This observational case\u2013control study included 132 Caucasian Italian patients with cutaneous melanoma and 312 healthy controls. The rs11549465 polymorphism was genotyped by genomic DNA restriction fragment analysis. Logistic regression provided age- and sex-adjusted and mutually adjusted estimates. Results: Genotype and allele frequencies did not differ between patients and controls. Within the melanoma cohort, smoking for \u226520 years remained associated with metastatic disease after adjustment for BMI \u2265 25 kg\/m2, age at diagnosis, and sex (aOR = 3.12, p = 0.006), whereas BMI did not (aOR = 1.23, p = 0.612). Compared with healthy controls, metastatic melanoma was independently associated with BMI \u2265 25 kg\/m2 (aOR = 2.26, p = 0.010) and smoking for \u226520 years (aOR = 3.85, p &lt; 0.001). Mean pack-years were higher in melanoma patients than controls (9.4 \u00b1 16.7 vs. 5.1 \u00b1 12.2; p = 0.002), and \u226510 and \u226520 pack-years remained associated after age- and sex-adjustment (aOR = 2.19, p = 0.001 and aOR = 3.31, p &lt; 0.001, respectively). Mean pack-years were higher in MetM than NMetM (13.1 \u00b1 21.0 vs. 5.9 \u00b1 10.0; p = 0.013), and \u226520 pack-years was associated with MetM (OR = 3.05, p = 0.017). Adjusted associations with head\/neck melanoma (n = 13) were observed for CC plus BMI \u2265 30 kg\/m2 (aOR = 9.07, p &lt; 0.001), \u226520 cigarette\/day (aOR = 5.96, p = 0.004), \u226520 years smoking (aOR = 6.64, p = 0.003), and other smoking measures. Conclusions: To our knowledge, this is the first report on the interplay between the rs11549465 polymorphism and cutaneous melanoma. HIF1A rs11549465 was not independently associated with melanoma susceptibility. Associations involving smoking, BMI, joint genotype\u2013lifestyle exposures, and anatomical localization had wide confidence intervals and were exploratory; small subgroups and multiple comparisons require cautious interpretation and independent validation.<\/jats:p>","DOI":"10.3390\/cancers18172787","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T12:03:43Z","timestamp":1787832223000},"page":"2787","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hypoxia-Inducible Factor-1\u03b1 Gene (HIF1A) rs11549465 (1772 C&gt;T) Polymorphism, Body Mass Index, Smoking, and Cutaneous Melanoma: An Observational Case\u2013Control Study"],"prefix":"10.3390","volume":"18","author":[{"given":"Cinzia","family":"Buligan","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Udine, Piazzale Kolbe 4, 33100 Udine, Italy"},{"name":"Institute of Dermatology, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), Santa Maria della Misericordia, Friuli Centrale University Healthcare Hospital of Udine, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Maione","sequence":"additional","affiliation":[{"name":"Dermatology Clinic, Department of Medical Sciences, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Petris","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Udine, Piazzale Kolbe 4, 33100 Udine, Italy"},{"name":"Fondazione Italiana Fegato ETS\u2014Italian Liver Foundation ETS, 34149 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2392-9504","authenticated-orcid":false,"given":"Giuseppe","family":"Stinco","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Udine, Piazzale Kolbe 4, 33100 Udine, Italy"},{"name":"Institute of Dermatology, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), Santa Maria della Misericordia, Friuli Centrale University Healthcare Hospital of Udine, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Cauci","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Udine, Piazzale Kolbe 4, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6816","DOI":"10.1097\/JS9.0000000000002908","article-title":"Burden trend and forecasting analysis of malignant skin melanoma from 1990 to 2021","volume":"111","author":"Wang","year":"2025","journal-title":"Int. J. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/S0140-6736(23)00821-8","article-title":"Cutaneous melanoma","volume":"402","author":"Long","year":"2023","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1001\/jama.2025.13074","article-title":"Cutaneous melanoma: A review","volume":"334","author":"Joshi","year":"2025","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"102990","DOI":"10.1016\/j.canep.2026.102990","article-title":"Estimates of cancer incidence to 2025 in Italy: Numbers and rates","volume":"101","author":"Fabiano","year":"2026","journal-title":"Cancer Epidemiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1097\/CMR.0000000000001029","article-title":"Multiple primary melanomas in Udine, northeastern Italy: A focus on epidemiology and new risk factors","volume":"35","author":"Guglielmo","year":"2025","journal-title":"Melanoma Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1111\/jdv.70111","article-title":"Precision medicine in cutaneous melanoma-A comprehensive review","volume":"40","author":"Reitmajer","year":"2026","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/978-3-319-22539-5_2","article-title":"Melanoma epidemiology and prevention","volume":"167","author":"Berwick","year":"2016","journal-title":"Cancer Treat. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.jaad.2021.12.066","article-title":"Skin cancer: Primary, secondary, and tertiary prevention. Part I","volume":"87","author":"Perez","year":"2022","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.jaad.2022.01.053","article-title":"Skin cancer: Primary, secondary, and tertiary prevention. Part II","volume":"87","author":"Rojas","year":"2022","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"106132","DOI":"10.18632\/oncotarget.22190","article-title":"Immune system and melanoma biology: A balance between immunosurveillance and immune escape","volume":"8","author":"Passarelli","year":"2017","journal-title":"Oncotarget"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1001\/jamadermatol.2018.3964","article-title":"Association of phenotypic characteristics and UV radiation exposure with risk of melanoma on different body sites","volume":"155","author":"Ghiasvand","year":"2019","journal-title":"JAMA Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8886","DOI":"10.3390\/curroncol29110699","article-title":"An epidemiological update on indoor tanning and the risk of skin cancers","volume":"29","author":"Dessinioti","year":"2022","journal-title":"Curr. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"162","DOI":"10.20892\/j.issn.2095-3941.2017.0020","article-title":"Immunohistochemical evaluation of vitamin D receptor (VDR) expression in cutaneous melanoma tissues and four VDR gene polymorphisms","volume":"14","author":"Stinco","year":"2017","journal-title":"Cancer Biol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"302","DOI":"10.20892\/j.issn.2095-3941.2017.0064","article-title":"BsmI (rs1544410) and FokI (rs2228570) vitamin D receptor polymorphisms, smoking, and body mass index as risk factors of cutaneous malignant melanoma in northeast Italy","volume":"14","author":"Cauci","year":"2017","journal-title":"Cancer Biol. Med."},{"key":"ref_15","first-page":"5759","article-title":"Interleukin 1 receptor antagonist gene variable number of tandem repeats polymorphism and cutaneous melanoma","volume":"18","author":"Cauci","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1186\/s12940-022-00944-x","article-title":"Per- and polyfluoroalkyl substances (PFAS) exposure in melanoma patients: A retrospective study on prognosis and histological features","volume":"21","author":"Cavallin","year":"2022","journal-title":"Environ. Health"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Emanuelli, M., Sartini, D., Molinelli, E., Campagna, R., Pozzi, V., Salvolini, E., Simonetti, O., Campanati, A., and Offidani, A. (2022). The double-edged sword of oxidative stress in skin damage and melanoma: From physiopathology to therapeutical approaches. Antioxidants, 11.","DOI":"10.3390\/antiox11040612"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.cell.2012.06.024","article-title":"A landscape of driver mutations in melanoma","volume":"150","author":"Hodis","year":"2012","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1111\/j.1755-148X.2012.01008.x","article-title":"Inflammasome polymorphisms confer susceptibility to sporadic malignant melanoma","volume":"25","author":"Verma","year":"2012","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Cauci, S., Buligan, C., Bazzichetto, L., Petris, G., and Stinco, G. (2026). Interleukin-1\u03b2 Gene (IL1B) rs1143634 (+3954 C>T) Polymorphism and Cutaneous Melanoma Risk: An Observational Case-Control Study in Northeast Italy. Genes, 17.","DOI":"10.3390\/genes17070786"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Cauci, S., Buligan, C., Nacci, P., Petris, G., and Stinco, G. (2026). Interleukin-1\u03b2 Gene (IL-1B) rs16944 (-511 C > T) Promoter Polymorphism Is Associated with Cutaneous Melanoma Susceptibility, Stage, and Anatomical Localization in a Northern Italian Case-Control Study. Curr. Oncol., 33.","DOI":"10.3390\/curroncol33070436"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/s41588-020-0611-8","article-title":"Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility","volume":"52","author":"Landi","year":"2020","journal-title":"Nat. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Dong, Y., Wei, J., Yang, F., Qu, Y., Huang, J., and Shi, D. (2023). Nutrient-based approaches for melanoma: Prevention and therapeutic insights. Nutrients, 15.","DOI":"10.3390\/nu15204483"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Pec, J., Paj\u0105k, W., Kleinrok, J., Rusztyn, K., Flieger, J., Teresi\u0144ska, B., Forma, A., and Baj, J. (2026). The role of vitamins and micronutrients in the prevention of melanoma: A review of current evidence. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27031428"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"34424","DOI":"10.1038\/srep34424","article-title":"Cigarette smoke reversibly activates hypoxia-inducible factor 1 in a reactive oxygen species-dependent manner","volume":"6","author":"Daijo","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.semcancer.2025.07.007","article-title":"Obesity-driven inflammation and cancer risk: A comprehensive review","volume":"114","author":"Lamabadusuriya","year":"2025","journal-title":"Semin. Cancer Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e159839","DOI":"10.1172\/JCI159839","article-title":"Hypoxia-inducible factors: Cancer progression and clinical translation","volume":"132","author":"Wicks","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ashraf, A., and Bruce, E.D. (2026). A review of HIF-1\u03b1-mediated integration of metabolic reprogramming, mitochondrial function, and PI3K\/Akt-MAPK-Nrf2-NF-\u03baB signaling. Antioxidants, 15.","DOI":"10.3390\/antiox15030378"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/j.bbadis.2012.02.004","article-title":"Mitochondrial reactive oxygen species mediates nicotine-induced hypoxia-inducible factor-1\u03b1 expression in human non-small cell lung cancer cells","volume":"1822","author":"Guo","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.gendis.2023.02.039","article-title":"HIF-1\u03b1 signaling: Essential roles in tumorigenesis and implications in targeted therapies","volume":"11","author":"Zhao","year":"2023","journal-title":"Genes Dis."},{"key":"ref_31","first-page":"e70700","article-title":"Hypoxia-inducible factor 1-alpha (HIF-1\u03b1) and cancer: Mechanisms of tumor hypoxia and therapeutic targeting","volume":"16","author":"Basheeruddin","year":"2024","journal-title":"Cureus"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Shi, S., Ou, X., Liu, C., Wen, H., and Ke, J. (2025). Research progress of HIF-1a on immunotherapy outcomes in immune vascular microenvironment. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1549276"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Tucci, M., Passarelli, A., Mannavola, F., Felici, C., Stucci, L.S., Cives, M., and Silvestris, F. (2019). Immune system evasion as hallmark of melanoma progression: The role of dendritic cells. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.01148"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Shirley, C.A., Chhabra, G., Amiri, D., Chang, H., and Ahmad, N. (2024). Immune escape and metastasis mechanisms in melanoma: Breaking down the dichotomy. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1336023"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/1476-4598-8-104","article-title":"Expression and function of hypoxia inducible factor-1 alpha in human melanoma under non-hypoxic conditions","volume":"8","author":"Mills","year":"2009","journal-title":"Mol. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Mart\u00ed-D\u00edaz, R., Montenegro, M.F., Cabezas-Herrera, J., Goding, C.R., Rodr\u00edguez-L\u00f3pez, J.N., and S\u00e1nchez-Del-Campo, L. (2020). Acriflavine, a potent inhibitor of HIF-1\u03b1, disturbs glucose metabolism and suppresses ATF4-protective pathways in melanoma under non-hypoxic conditions. Cancers, 13.","DOI":"10.3390\/cancers13010102"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1186\/1756-9966-28-159","article-title":"Hypoxia-inducible factor-1alpha gene polymorphisms and cancer risk: A meta-analysis","volume":"28","author":"Zhao","year":"2009","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Yan, Q., Chen, P., Wang, S., Liu, N., Zhao, P., and Gu, A. (2014). Association between HIF-1\u03b1 C1772T\/G1790A polymorphisms and cancer susceptibility: An updated systematic review and meta-analysis based on 40 case-control studies. BMC Cancer, 14.","DOI":"10.1186\/1471-2407-14-950"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5955","DOI":"10.7150\/jca.35716","article-title":"HIF-1\u03b1 rs11549465 C>T polymorphism contributes to increased cancer susceptibility: Evidence from 49 studies","volume":"10","author":"Li","year":"2019","journal-title":"J. Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"141141","DOI":"10.1016\/j.jhazmat.2026.141141","article-title":"Heavy metal exposure and all health outcomes: An umbrella review of meta-analyses","volume":"503","author":"Lee","year":"2026","journal-title":"J. Hazard. Mater."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1080\/14737140.2018.1489246","article-title":"The eighth edition American Joint Committee on Cancer (AJCC) melanoma staging system: Implications for melanoma treatment and care","volume":"18","author":"Keung","year":"2018","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1093\/jnci\/81.24.1893","article-title":"Model predicting survival in stage I melanoma based on tumor progression","volume":"81","author":"Clark","year":"1989","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1001\/archderm.1988.01670060015008","article-title":"The validity and practicality of sun-reactive skin types I through VI","volume":"124","author":"Fitzpatrick","year":"1988","journal-title":"Arch. Dermatol."},{"key":"ref_44","unstructured":"Centers for Disease Control and Prevention (2026, May 25). Adult BMI Categories. BMI. CDC, Available online: https:\/\/www.cdc.gov."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.trsl.2011.09.003","article-title":"Association of hypoxia inducible factor-1\u03b1 polymorphisms with susceptibility to non-small-cell lung cancer","volume":"159","author":"Kuo","year":"2012","journal-title":"Transl. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"403","DOI":"10.2478\/raon-2025-0049","article-title":"Genetic variability of HIF1A and response to treatment with cisplatin in combination with pemetrexed or gemcitabine in patients with malignant mesothelioma","volume":"59","author":"Setina","year":"2025","journal-title":"Radiol. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1002\/mc.20655","article-title":"Single nucleotide polymorphisms in the hypoxia-inducible factor-1 gene and colorectal cancer risk","volume":"49","author":"Knechtel","year":"2010","journal-title":"Mol. Carcinog."},{"key":"ref_48","unstructured":"National Library of Medicine (2026, May 25). Rs11549465 RefSNP Report, Available online: https:\/\/www.ncbi.nlm.nih.gov\/snp\/rs11549465."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Gorodetska, I., Schulz, A., Behre, G., and Dubrovska, A. (2025). Confronting Melanoma Radioresistance: Mechanisms and Therapeutic Strategies. Cancers, 17.","DOI":"10.3390\/cancers17162648"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"21329","DOI":"10.18632\/aging.103871","article-title":"Different polymorphisms in HIF-1\u03b1 may exhibit different effects on cancer risk in Asians: Evidence from nearly forty thousand participants","volume":"12","author":"Liu","year":"2020","journal-title":"Aging"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1089\/gtmb.2013.0325","article-title":"HIF-1\u03b1 C1772T polymorphism and gastrointestinal tract cancer risk: A meta-analysis and meta-regression analysis","volume":"17","author":"Xu","year":"2013","journal-title":"Genet. Test. Mol. Biomark."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s11154-016-9393-9","article-title":"Obesity as a risk factor for malignant melanoma and non-melanoma skin cancer","volume":"17","author":"Karimi","year":"2016","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.semcancer.2023.02.010","article-title":"Obesity and immune-checkpoint inhibitors in advanced melanoma: A meta-analysis of survival outcomes from clinical studies","volume":"91","author":"Roccuzzo","year":"2023","journal-title":"Semin. Cancer Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.annonc.2020.12.012","article-title":"Relevance of body mass index as a predictor of systemic therapy outcomes in metastatic melanoma: Analysis of the MelBase French cohort data\u2606","volume":"32","author":"Dalle","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1038\/s42255-026-01542-8","article-title":"Adiposity and cancer: Systematic review and meta-analysis","volume":"8","author":"Watts","year":"2026","journal-title":"Nat. Metab."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"E877-85","DOI":"10.1152\/ajpendo.00626.2010","article-title":"Regulation of HIF-1\u03b1 activity in adipose tissue by obesity-associated factors: Adipogenesis, insulin, and hypoxia","volume":"300","author":"He","year":"2011","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1007\/s00125-013-2885-1","article-title":"Adipose tissue hypoxia induces inflammatory M1 polarity of macrophages in an HIF-1\u03b1-dependent and HIF-1\u03b1-independent manner in obese mice","volume":"56","author":"Fujisaka","year":"2013","journal-title":"Diabetologia"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"71","DOI":"10.3892\/wasj.2024.286","article-title":"Exploring the complex relationship between HIF-1 (rs11549465) and NF\u0138B1 (rs28362491) variations and obesity (Review)","volume":"6","author":"Alwardat","year":"2024","journal-title":"World Acad. Sci. J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1111\/j.1468-3083.2009.03556.x","article-title":"A multilocus candidate approach identifies ACE and HIF1A as susceptibility genes for cellulite","volume":"24","author":"Emanuele","year":"2010","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1093\/carcin\/bgg132","article-title":"Hypoxia-inducible factor-1alpha polymorphisms associated with enhanced transactivation capacity, implying clinical significance","volume":"24","author":"Tanimoto","year":"2003","journal-title":"Carcinogenesis"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1007\/s10389-020-01443-4","article-title":"A review of tobacco abuse and its epidemiological consequences","volume":"30","author":"Omare","year":"2022","journal-title":"Z. Gesundh. Wiss."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1515\/reveh-2022-0013","article-title":"A review of the characteristic properties of selected tobacco chemicals and their associated etiological risks","volume":"38","author":"Maiyo","year":"2022","journal-title":"Rev. Environ. Health"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"119928","DOI":"10.1016\/j.envpol.2022.119928","article-title":"High expression of HIF-1\u03b1 alleviates benzene-induced hematopoietic toxicity and immunosuppression in mice","volume":"311","author":"Huang","year":"2022","journal-title":"Environ. Pollut."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1002\/jat.1679","article-title":"Regulation of cigarette smoke-mediated mucin expression by hypoxia-inducible factor-1\u03b1 via epidermal growth factor receptor-mediated signaling pathways","volume":"32","author":"Yu","year":"2012","journal-title":"J. Appl. Toxicol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"115062","DOI":"10.1016\/j.intimp.2025.115062","article-title":"HIF-1\u03b1 protects cigarette-induced airway epithelial cell apoptosis in COPD by activating REDD1","volume":"161","author":"Hua","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Kida, N., Matsuo, Y., Hashimoto, Y., Nishi, K., Tsuzuki-Nakao, T., Bono, H., Maruyama, T., Hirota, K., and Okada, H. (2021). Cigarette smoke extract activates hypoxia-inducible factors in a reactive oxygen species-dependent manner in stroma cells from human endometrium. Antioxidants, 10.","DOI":"10.3390\/antiox10010048"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"107178","DOI":"10.1016\/j.jenvrad.2023.107178","article-title":"Dosimetry in the lungs of \u03b1-particles (210Po) and \u03b2-particles (210Pb) present in the tobacco smoke of conventional cigarettes and heated tobacco products","volume":"263","author":"Desorgher","year":"2023","journal-title":"J. Environ. Radioact."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"116101","DOI":"10.1016\/j.fct.2026.116101","article-title":"Chemometric assessment of the radiotoxic burden: 210Po in conventional, slim, and heated tobacco products","volume":"213","author":"Wieczorek","year":"2026","journal-title":"Food Chem. Toxicol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1080\/15376510902740978","article-title":"210Po Log-normal distribution in human urines: Survey from central Italy people","volume":"19","author":"Sisti","year":"2009","journal-title":"Toxicol. Mech. Methods"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"102872","DOI":"10.1016\/j.eclinm.2024.102872","article-title":"Outcomes for smokers who develop melanoma: A systematic review and meta-analysis","volume":"77","author":"Friedman","year":"2024","journal-title":"eClinicalMedicine"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Arisi, M., Zane, C., Caravello, S., Rovati, C., Zanca, A., Venturini, M., and Calzavara-Pinton, P. (2018). Sun exposure and melanoma, certainties and weaknesses of the present knowledge. Front. Med., 5.","DOI":"10.3389\/fmed.2018.00235"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1111\/bjd.13489","article-title":"Clinical and histological features of head and neck melanoma: A population-based study in France","volume":"172","author":"Dabouz","year":"2015","journal-title":"Br. J. Dermatol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1002\/jvc2.250","article-title":"Head-neck melanoma: Clinical, histopathological and prognostic features of an Italian multicentric study","volume":"3","author":"Schipani","year":"2024","journal-title":"JEADV Clin. Pract."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1136\/oem.2002.006320","article-title":"Cutaneous melanoma: Hints from occupational risks by anatomic site in Swedish men","volume":"61","author":"Gustavsson","year":"2004","journal-title":"Occup. Environ. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1002\/ijc.28603","article-title":"Occupational sun exposure and risk of melanoma according to anatomical site","volume":"134","author":"Vuong","year":"2014","journal-title":"Int. J. Cancer"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"107","DOI":"10.26574\/maedica.2026.21.1.107","article-title":"Sun exposure patterns affect melanoma location but not prognostic features","volume":"21","author":"Vasiu","year":"2026","journal-title":"Maedica"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1097\/CMR.0000000000001075","article-title":"Divergent pathways of melanoma development: Evidence from a Southern European cohort","volume":"36","author":"Stratigos","year":"2026","journal-title":"Melanoma Res."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Crosby, B., Guerra, M., Crosby, A., Linza, B., Lourdault, K., and Essner, R. (2026). Biomarkers in Melanoma: Updates in Prognosis and Management. Cancers, 18.","DOI":"10.3390\/cancers18121992"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/S1470-2045(24)00076-7","article-title":"Development and validation of a novel model to predict recurrence-free survival and melanoma-specific survival after sentinel lymph node biopsy in patients with melanoma: An international, retrospective, multicentre analysis","volume":"25","author":"Stassen","year":"2024","journal-title":"Lancet Oncol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1096\/fj.03-0329fje","article-title":"IL-1beta-mediated up-regulation of HIF-1alpha via an NFkappaB\/COX-2 pathway identifies HIF-1 as a critical link between inflammation and oncogenesis","volume":"17","author":"Jung","year":"2003","journal-title":"FASEB J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.ctrv.2006.05.003","article-title":"Oncological implications of hypoxia inducible factor-1\u03b1 (HIF-1\u03b1) expression","volume":"32","author":"Joyce","year":"2006","journal-title":"Cancer Treat. Rev."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s13062-024-00487-w","article-title":"Hypoxia-induced activation of HIF-1alpha\/IL-1beta axis in microglia promotes glioma progression via NF-\u03baB-mediated upregulation of heparanase expression","volume":"19","author":"Si","year":"2024","journal-title":"Biol. Direct"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Murugesan, V., Thuraisingam, T., and Radzioch, D. (2026). From Excision to Immunity: The Full Spectrum of Modern Melanoma Treatments. Cancers, 18.","DOI":"10.3390\/cancers18132043"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e20251009","DOI":"10.1084\/jem.20251009","article-title":"Targeting conserved domains of hypoxia-inducible factors for cancer therapy","volume":"223","author":"Salman","year":"2026","journal-title":"J. Exp. Med."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Prka\u010din, I., Mokos, M., Ferara, N., and \u0160itum, M. (2024). Melanoma\u2019s New Frontier: Exploring the Latest Advances in Blood-Based Biomarkers for Melanoma. Cancers, 16.","DOI":"10.3390\/cancers16244219"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/17\/2787\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T04:50:21Z","timestamp":1787979021000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/17\/2787"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,27]]},"references-count":85,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cancers18172787"],"URL":"https:\/\/doi.org\/10.3390\/cancers18172787","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,27]]}}}