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© 2005 Oxford University Press
ARTICLE |
Lifetime Risk of Melanoma in CDKN2A Mutation Carriers in a Population-Based Sample
for the Genes Environment and Melanoma (GEM) Study Group
Affiliations of authors: Memorial Sloan–Kettering Cancer Center, New York, NY (CBB, IO, AJH, NM, KB, MB); The University of Sydney and Cancer Council New South Wales, Sydney, Australia (BKA, AK); Cancer Care Ontario, Toronto, Canada (LDM, LF); University of North Carolina at Chapel Hill, NC (RCM); University of Michigan, Ann Arbor, MI (SBG); University of California at Irvine, CA (HA-C); Centro per la Prevenzione Oncologia Torino, Piemonte, Italy (RZ); British Columbia Cancer Agency, Vancouver, Canada (RPG); Menzies Centre for Population Health Research, University of Tasmania, Hobart, Australia (TD); University of Pennsylvania, Philadelphia, PA (TRR); University of New Mexico, Albuquerque, NM (MB)
Correspondence to: Colin B. Begg, PhD, Memorial Sloan–Kettering Cancer Center, 307 East 63rd St., 3rd Floor, New York, NY 10021 (e-mail: beggc{at}mskcc.org).
Background: Germline mutations in the CDKN2A gene have been linked to melanoma incidence in many families with multiple cases of the disease. Previous studies of multiple-case families have indicated that the lifetime risk (i.e., penetrance) of melanoma in CDKN2A mutation carriers is very high, ranging from 58% in Europe to 91% in Australia by age 80 years. In this study, we examined lifetime melanoma risk among CDKN2A mutation carriers using carriers who were identified in a population-based study of melanoma. Methods: Probands for the study were incident case patients with either first or subsequent melanoma who were identified in nine geographic regions in Australia, Canada, the United States, and Italy. A total of 3626 probands (53% participation rate) with adequate DNA for analysis were recruited and genotyped for CDKN2A mutations. From the 3550 probands whose DNA could be amplified by polymerase chain reaction of CDKN2A exons 1
, 2, and 3 and surrounding regions, 65 mutation carriers were identified. Melanoma histories in first-degree relatives of these probands were used to calculate the lifetime risk in CDKN2A mutation carriers using the kin–cohort method. Results: The risk of melanoma in CDKN2A mutation carriers was approximately 14% (95% CI = 8% to 22%) by age 50 years, 24% (95% CI = 15% to 34%) by age 70 years, and 28% (95% CI = 18% to 40%) by age 80 years. Eighteen probands had three or more first-degree relatives with melanoma, but only one was a carrier of a CDKN2A mutation. Conclusions: CDKN2A mutation carriers in the general population have a much lower risk of melanoma than that suggested by estimates obtained from multiple-case families. The preponderance of familial clustering of melanoma occurs in families without identifiable mutations in CDKN2A.
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Editorial about this Article
- A Piece of the Melanoma Puzzle
- Alisa M. Goldstein and Margaret A. Tucker
J Natl Cancer Inst 2005 97: 1486-1487.[Extract] [Full Text] [PDF]
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