Abstract
A family history of cutaneous melanoma ('melanoma') is a well-established risk factor for melanoma. However, less is known about the possible familial associations of melanoma with other discordant cancers. A risk for discordant cancer may provide useful information about shared genetic and environmental risk factors and it may be relevant background data in clinical genetic counseling. Using the Swedish Family-Cancer Database, we assessed the relative risk (RR) for any cancer in families with increasing numbers of first-degree relatives diagnosed with melanoma, including multiple melanoma, and in reverse order RR for melanoma in families of multiple discordant cancers. Close to 9% of melanoma was familial; among these 92% were in 2-case families and 8% in families with 3 cases or more. Cancers that were associated with melanoma, in at least two independent analyses, included breast, prostate, colorectal, skin and nervous system cancers. Other associations included cancer of unknown primary, acute myeloid leukemia/myelofibrosis and Waldenström macroglobulinemia/myeloma. Significant results, which appear biologically plausible, were also obtained for rare nasal melanoma and mesothelioma. Although small samples sizes and multiple comparisons were of concern, many of the above associations were internally consistent and provide new diverse leads for discordant familial association of melanoma.