{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T20:10:46Z","timestamp":1762459846492,"version":"build-2065373602"},"reference-count":83,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,3,5]],"date-time":"2020-03-05T00:00:00Z","timestamp":1583366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA 160756"],"award-info":[{"award-number":["CA 160756"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Melanoma Research Alliance Young Investigation Award","award":["509278"],"award-info":[{"award-number":["509278"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The mechanism of gender disparity in cutaneous melanoma incidence remains unclear. Steroid hormones including estrogens have long been implicated in the course of melanoma, but the conclusion is controversial. Estrogen receptors (ERs) and insulin-like growth factor 1 receptor (IGF1R) show extensive crosstalk in cancer development, but how the ER\/IGF1R network impacts melanoma is currently unclear. Here we studied the melanoma associations of selected SNPs from the ER\/IGF1R network. Part of the International Genes, Environment, and Melanoma (GEM) cohort was used as a discovery set, and the Gene Environment Association Studies Initiative (GENEVA) dataset served as a validation set. Based on the associations with other malignant disease conditions, thirteen single nucleotide polymorphism (SNP) variants in ESR1, ESR2, IGF1, and IGF1R were selected for candidate gene association analyses. The rs1520220 in IGF1 and rs2229765 in IGF1R variants were significantly associated with melanoma risk in the GEM dataset after Benjamini-Hochberg multiple comparison correction, although they were not validated in the GENEVA set. The discrepancy may be caused by the multiple melanoma characteristics in the GEM patients. Further analysis of gender disparity was carried out for IGF1 and IGF1R SNPs in the GEM dataset. The GG phenotype in IGF1 rs1520220 (recessive model) presented an increased risk of melanoma (OR = 8.11, 95% CI: 2.20, 52.5, p = 0.006) in men but a significant opposite effect in women (OR = 0.15, 95% CI: 0.018, 0.86, p = 0.045). The AA genotype in IGF1R rs2229765 (recessive model) showed a significant protective effect in men (OR = 0.24, 95% CI: 0.07, 0.64, p = 0.008) and no effect in women. Results from the current study are warranted for further validation.<\/jats:p>","DOI":"10.3390\/ijms21051776","type":"journal-article","created":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T07:33:46Z","timestamp":1583480026000},"page":"1776","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A Possible Link of Genetic Variations in ER\/IGF1R Pathway and Risk of Melanoma"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6383-5983","authenticated-orcid":false,"given":"Tze-An","family":"Yuan","sequence":"first","affiliation":[{"name":"Program in Public Health, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vandy","family":"Yourk","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior, School of Biological Sciences, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Farhat","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, The Henry Samueli School of Engineering, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine L.","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Ecology and Evolutionary Biology, University of California Los Angeles, Los Angeles, CA 90024, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank L.","family":"Meyskens","sequence":"additional","affiliation":[{"name":"Program in Public Health, University of California Irvine, Irvine, CA 92697, USA"},{"name":"Department of Medicine, School of Medicine, University of California Irvine, Irvine, CA 92697, USA"},{"name":"Chao Family Comprehensive Cancer Center, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Liu-Smith","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, University of California Irvine, Irvine, CA 92697, USA"},{"name":"Chao Family Comprehensive Cancer Center, Irvine, CA 92697, USA"},{"name":"Department of Epidemiology, School of Medicine, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,5]]},"reference":[{"key":"ref_1","unstructured":"SEER (2019, June 28). 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