{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T11:56:30Z","timestamp":1789386990529,"version":"build-2803163510"},"reference-count":68,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,2,3]],"date-time":"2009-02-03T00:00:00Z","timestamp":1233619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2009,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Human pigmentation is a polygenic quantitative trait with high heritability. Although a large number of single nucleotide polymorphisms (SNPs) have been identified in pigmentation genes, very few SNPs have been examined in relation to human pigmentary phenotypes and skin cancer risk. We evaluated the associations between 15 SNPs in 8 candidate pigmentation genes (<jats:italic>TYR, TYRP1, OCA2, SLC24A5, SLC45A2, POMC, ASIP<\/jats:italic> and <jats:italic>ATRN<\/jats:italic>) and both pigmentary phenotypes (hair color, skin color and tanning ability) and skin cancer risk in a nested case\u2010control study of Caucasians within the Nurses' Health Study (NHS) among 218 melanoma cases, 285 squamous cell carcinoma (SCC) cases, 300 basal cell carcinoma (BCC) cases and 870 common controls. We found that the <jats:italic>TYR<\/jats:italic> Arg402Gln variant was significantly associated with skin color (<jats:italic>p<\/jats:italic>\u2010value = 7.7 \u00d7 10<jats:sup>\u22124<\/jats:sup>) and tanning ability (<jats:italic>p<\/jats:italic>\u2010value = 7.3 \u00d7 10<jats:sup>\u22124<\/jats:sup>); the <jats:italic>SLC45A2<\/jats:italic> Phe374Leu variant was significantly associated with hair color (black to blonde) (<jats:italic>p<\/jats:italic>\u2010value = 2.4 \u00d7 10<jats:sup>\u22127<\/jats:sup>), skin color (<jats:italic>p<\/jats:italic>\u2010value = 1.1 \u00d7 10<jats:sup>\u22127<\/jats:sup>) and tanning ability (<jats:italic>p<\/jats:italic>\u2010value = 2.5 \u00d7 10<jats:sup>\u22124<\/jats:sup>). These associations remained significant after controlling for <jats:italic>MC1R<\/jats:italic> variants. No significant associations were found between these polymorphisms and the risk of skin cancer. We observed that the <jats:italic>TYRP1<\/jats:italic> rs1408799 and <jats:italic>SLC45A2<\/jats:italic> 1721 C&gt;G were associated with melanoma risk (OR, 0.77; 95% CI, 0.60\u20130.98 and OR, 0.75; 95% CI, 0.60\u20130.95, respectively). The <jats:italic>TYR<\/jats:italic> Ser192Tyr was associated with SCC risk (OR, 1.23; 95% CI, 1.00\u20131.50). The <jats:italic>TYR<\/jats:italic> haplotype carrying only the Arg402Gln variant allele was significantly associated with SCC risk (OR, 1.35; 95% CI, 1.04\u20131.74). The <jats:italic>OCA2<\/jats:italic> Arg419Gln and <jats:italic>ASIP<\/jats:italic> g.8818 A&gt;G were associated with BCC risk (OR, 1.50; 95% CI, 1.06\u20132.13 and OR, 0.73; 95% CI, 0.53\u20131.00, respectively). The haplotype near <jats:italic>ASIP<\/jats:italic> (rs4911414[T] and rs1015362[G]) was significantly associated with fair skin color (OR, 2.28; 95% CI, 1.46\u20133.57) as well as the risks of melanoma (OR, 1.68; 95% CI, 1.18\u20132.39) and SCC (OR, 1.54; 95% CI, 1.08\u20132.19). These associations remained similar after adjusting for pigmentary phenotypes and <jats:italic>MC1R<\/jats:italic> variants. The statistical power of our study was modest and additional studies are warranted to confirm the associations observed in the present study. Our study provides evidence for the contribution of pigmentation genetic variants, in addition to the <jats:italic>MC1R<\/jats:italic> variants, to variation in human pigmentary phenotypes and possibly the development of skin cancer. \u00a9 2009 UICC<\/jats:p>","DOI":"10.1002\/ijc.24327","type":"journal-article","created":{"date-parts":[[2009,2,3]],"date-time":"2009-02-03T14:38:35Z","timestamp":1233671915000},"page":"909-917","source":"Crossref","is-referenced-by-count":177,"title":["Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in Caucasians"],"prefix":"10.1002","volume":"125","author":[{"given":"Hongmei","family":"Nan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kraft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Hunter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiali","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,6,11]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajpa.1330550207"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.1964.tb00457.x"},{"key":"e_1_2_6_4_2","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1006\/jhev.2000.0403","article-title":"The evolution of human skin coloration","volume":"39","author":"Jablonski NG","year":"2000","journal-title":"JHum Evol"},{"key":"e_1_2_6_5_2","volume-title":"The pigmentary system\u2014physiology and pathophysiology","author":"Nordlund JJ","year":"1998"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ge.28.120194.001201"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117224"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0749.13.s8.10.x"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05098"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0749.1996.tb00109.x"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/4.2.223"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/18217"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/83741"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1995.1211"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(01)00694-1"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0749.13.s8.20.x"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.suppl_1.1469"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2000.5092"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2000.00108.x"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/361072a0"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2004.04.033"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1116238"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-003-1069-0"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyl197"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.163"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.161"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000074"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.160"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2007.13"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.22074"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a114319"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/1047-2797(90)90015-K"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.17.2531"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.21.2397"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.37.110801.143233"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.20061"},{"key":"e_1_2_6_37_2","unstructured":"GaudermanWJ MorrisonJM. 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