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In this study, we examine their association with the risk of developing metastases of uveal melanoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data on metabolic factors, medications, serum leptin levels, tumour leptin receptor RNA expression and clinical outcomes were examined in three cohorts. HRs for metastasis and cumulative incidences of melanoma-related mortality were calculated, and the levels of tumour leptin receptor expression were compared with prognostic factors including<jats:italic>BAP1<\/jats:italic>mutation, and tumour cell morphology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 581 patients in the main cohort, 116 (20%) were obese and 7 (1 %) had metastatic disease at presentation. In univariate Cox regressions, tumour diameter, diabetes type II and use of insulin were associated with metastases, but patients with obesity had a lower risk. The beneficial prognostic implication of obesity was retained in multivariate regressions. In competing risk analyses, the incidence of melanoma-related mortality was significantly lower for patients with obesity. Serum leptin levels\u2265median were associated with a reduced risk for metastasis, independent of patient sex and cancer stage in a separate cohort (n=80). Similarly, in a third cohort (n=80), tumours with<jats:italic>BAP1<\/jats:italic>mutation and epithelioid cells had higher leptin receptor RNA expression levels, which have a negative correlation with serum leptin levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Obesity and elevated serum leptin levels are associated with a lower risk for developing metastases and dying from uveal melanoma.<\/jats:p><\/jats:sec>","DOI":"10.1136\/bjo-2022-322877","type":"journal-article","created":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T17:20:14Z","timestamp":1680888014000},"page":"bjo-2022-322877","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Obesity paradox in uveal melanoma: high body mass index is associated with low metastatic risk"],"prefix":"10.1136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2533-3103","authenticated-orcid":false,"given":"Shiva","family":"Sabazade","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrianna","family":"Opalko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Herrspiegel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor Torgny","family":"Gill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Plastino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helder","family":"Andr\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9401-8911","authenticated-orcid":false,"given":"Gustav","family":"St\u00e5lhammar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,4,7]]},"reference":[{"key":"2023040710200720000_bjo-2022-322877v1.1","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2020-317949"},{"key":"2023040710200720000_bjo-2022-322877v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/s43856-022-00107-6"},{"key":"2023040710200720000_bjo-2022-322877v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(00)00182-2"},{"key":"2023040710200720000_bjo-2022-322877v1.4","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0000000000000575"},{"key":"2023040710200720000_bjo-2022-322877v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2017.07.003"},{"key":"2023040710200720000_bjo-2022-322877v1.6","doi-asserted-by":"crossref","first-page":"2784","DOI":"10.1002\/cam4.2167","article-title":"Expression of immune checkpoint receptors indoleamine 2,3-dioxygenase and T cell Ig and ITIM domain in metastatic versus nonmetastatic choroidal melanoma","volume":"8","author":"St\u00e5lhammar","year":"2019","journal-title":"Cancer Med"},{"key":"2023040710200720000_bjo-2022-322877v1.7","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-9280"},{"key":"2023040710200720000_bjo-2022-322877v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0198-8859(02)00389-0"},{"key":"2023040710200720000_bjo-2022-322877v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1998.646"},{"key":"2023040710200720000_bjo-2022-322877v1.10","doi-asserted-by":"publisher","DOI":"10.1076\/ceyr.19.5.426.5294"},{"key":"2023040710200720000_bjo-2022-322877v1.11","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s10911-015-9333-4","article-title":"New insights on COX-2 in chronic inflammation driving breast cancer growth and metastasis","volume":"20","author":"Hugo","year":"2015","journal-title":"J Mammary Gland Biol Neoplasia"},{"key":"2023040710200720000_bjo-2022-322877v1.12","doi-asserted-by":"crossref","unstructured":"Roubert A , Lyu L , Pfalzer A , et al . 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