The first two authors contributed equally to this article.
A melanoma case–control study
Article first published online: 4 NOV 2004
Published 2004 by the American Cancer Society
Volume 101, Issue 12, pages 2809–2816, 15 December 2004
How to Cite
Rutter, J. L., Bromley, C. M., Goldstein, A. M., Elder, D. E., Holly, E. A., Guerry, D., Hartge, P., Struewing, J. P., Hogg, D., Halpern, A., Sagebiel, R. W. and Tucker, M. A. (2004), Heterogeneity of risk for melanoma and pancreatic and digestive malignancies. Cancer, 101: 2809–2816. doi: 10.1002/cncr.20669
This article is a U.S. Government work and, as such, is in the public domain in the United States of America.
The opinions expressed herein do not necessarily reflect the views of the National Cancer Institute or the U.S. Government.
- Issue published online: 1 DEC 2004
- Article first published online: 4 NOV 2004
- Manuscript Accepted: 16 AUG 2004
- Manuscript Revised: 27 JUL 2004
- Manuscript Received: 19 APR 2004
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-associated malignancies and evaluated the familial heterogeneity of melanomas, pancreatic malignancies, and gastrointestinal malignancies.
The authors obtained patient histories of malignancy in first-degree relatives as part of a clinic-based case–control 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 (n = 133) were tested for germline mutations in CDKN2A.
The adjusted odds ratio associated with a family history of melanoma was 1.7 (95% confidence interval, 1.1–2.7). 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 CDKN2A 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.
Familial heterogeneity testing in the study population did not improve the selection of high-risk families for genetic study. Even in a large case–control 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.