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A. David Burden, MD, MRCP; John Newell, MSc; Nicola Andrew, MSc; Gina Kavanagh, MB, MRCP; J. Michael Connor, MD, FRCP; Rona M. MacKie, MD, FRCP

Arch Dermatol. 1999;135:261-265.

Objectives  To identify risk factors and the prognosis associated with the development of multiple primary melanoma (MPM).

Design  Case-comparison studies of subjects with MPM and single primary melanoma. Sequencing of CDKN2A in germline DNA.

Setting  Population-based study of patients with invasive melanoma in Scotland between 1979 and 1996.

Patients  For mortality studies, 108 patients with MPM and 216 single melanoma controls matched for age, sex, site, and tumor thickness. For risk factor studies, 48 patients with MPM and 48 single melanoma controls matched as above. For CDKN2A analysis, a sample of 23 subjects with MPM.

Results  The development of MPM was found not to be an independent prognostic factor. The risk of MPM was greatest in those with a family history of melanoma, with large numbers of benign nevi, and the presence of clinically or histologically atypical nevi. Germline mutations of CDKN2A were present in 6 of 23 patients with MPM and in 5 cases consisted of the base pair substitution Met53Ile.

Conclusions  The importance of MPM should be addressed in melanoma follow-up protocols. Those patients at greatest risk can be identified by a family history of melanoma and their mole pattern. Germline mutations in CDKN2A occur in both familial and sporadic MPM and further studies are required to determine the value of analysis of this gene in melanoma surveillance. Patients should be informed that the development of MPM does not adversely affect their prognosis.

From the Departments of Dermatology (Drs Burden and MacKie), Statistics (Mr Newell), and Medical Genetics (Ms Andrew and Dr Connor), University of Glasgow, Glasgow, and the Department of Dermatology, Royal Infirmary of Edinburgh, Edinburgh (Dr Kavanagh), Scotland.

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