{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T15:18:22Z","timestamp":1770823102330,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2004,11,4]],"date-time":"2004-11-04T00:00:00Z","timestamp":1099526400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2004,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Data addressing the interfamilial heterogeneity of melanoma are limited. In the current study, the authors assessed melanoma risk according to family history of melanoma and other melanoma\u2010associated malignancies and evaluated the familial heterogeneity of melanomas, pancreatic malignancies, and gastrointestinal malignancies.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>The authors obtained patient histories of malignancy in first\u2010degree relatives as part of a clinic\u2010based case\u2013control study. The case group included 737 newly diagnosed patients with invasive melanoma, and the control group included 1021 outpatients from clinics at the same medical centers. To assess heterogeneity of risk among families affected by melanoma, a nonparametric method was used to detect extrabinomial variation. In addition, selected patients with melanoma (<jats:italic>n<\/jats:italic> = 133) were tested for germline mutations in <jats:italic>CDKN2A<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>The adjusted odds ratio associated with a family history of melanoma was 1.7 (95% confidence interval, 1.1\u20132.7). Family histories of pancreatic, gastrointestinal, brain, breast, or lymphoproliferative disease did not increase the risk of melanoma significantly. Among case families, significant evidence of familial heterogeneity was found for melanomas, but not for pancreatic or gastrointestinal malignancies. Two mutations in <jats:italic>CDKN2A<\/jats:italic> previously associated with melanoma risk were identified among the 133 patients tested in the case group; mutation detection did not differ between families with low and high heterogeneity scores.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Familial heterogeneity testing in the study population did not improve the selection of high\u2010risk families for genetic study. Even in a large case\u2013control study, few families that had multiple members with melanoma were identified, and family members with pancreatic malignancies were rare. Cancer 2004. Published 2004 by the American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.20669","type":"journal-article","created":{"date-parts":[[2004,11,12]],"date-time":"2004-11-12T16:20:31Z","timestamp":1100276431000},"page":"2809-2816","source":"Crossref","is-referenced-by-count":29,"title":["Heterogeneity of risk for melanoma and pancreatic and digestive malignancies"],"prefix":"10.1002","volume":"101","author":[{"given":"Joni L.","family":"Rutter","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina M.","family":"Bromley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alisa M.","family":"Goldstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David E.","family":"Elder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth A.","family":"Holly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"IV","given":"DuPont","family":"Guerry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Hartge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffery P.","family":"Struewing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Hogg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allan","family":"Halpern","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard W.","family":"Sagebiel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret A.","family":"Tucker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,11,4]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.137.11.1493"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1999.17.10.3245"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206444"},{"key":"e_1_2_5_5_2","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1093\/oxfordjournals.aje.a116035","article-title":"Heterogeneity of breast cancer risk in families of young breast cancer patients and controls","volume":"134","author":"Schwartz AG","year":"1991","journal-title":"Am J Epidemiol."},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a117203"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/91.5.446"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1201\/b13271-33"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0196-97"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.2.209"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/94.12.894"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199510123331504"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19991112)83:4<441::AID-IJC2>3.0.CO;2-R"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/92.15.1260"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0215(20000915)87:6<809::AID-IJC8>3.0.CO;2-U"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.10159"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/91.15.1310"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.1.55"},{"key":"e_1_2_5_19_2","first-page":"2298","article-title":"Germ\u2010line deletion involving the INK4 locus in familial proneness to melanoma and nervous system tumours","volume":"58","author":"Bahuau M","year":"1998","journal-title":"Cancer Res."},{"key":"e_1_2_5_20_2","first-page":"537","article-title":"Further evidence for a locus for cutaneous malignant melanoma\u2010dysplastic nevus (CMM\/DN) on chromosome 1p, and evidence for genetic heterogeneity","volume":"52","author":"Goldstein AM","year":"1993","journal-title":"Am J Hum Genet."},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1997.03540420035026"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.1370010303"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.1370030710"},{"key":"e_1_2_5_24_2","volume-title":"National Cancer Institute Surveillance, Epidemiology, and End Results Program. 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