Increased risk of breast cancer in relatives of malignant melanoma patients from families with strong cancer familial aggregation.

The aim of this study was to evaluate the risk of occurrence of malignancies of different site of origin in patients with malignant melanoma (MM) of the skin and their first-degree relatives from families with cancer familial aggregations with unknown pathogenetic background (CFA). We analysed tumour spectrum and age at diagnosis of malignancies in 51 families with MM/CFA. In addition, we evaluated observed frequency (OF); expected frequency (EF); and relative risk (RR) of occurrence of malignancies in these families. In all cases peripheral blood examination of common Polish founder BRCA1 mutations was performed. In 25 families, we analysed loss of heterozygosity of BRCA1 and BRCA2 genes. We identified two subgroups of cases: 22 MM/CFA families with MM diagnosed before 55 years (< or =55 MM/CFA) and 29 MM/CFA families with MM diagnosed after 55 (>55 MM/CFA). In these families we observed increased proportion of breast cancers: 17.52% in the first subgroup (mean age of diagnosis 48.5) and 12.15% in the second subgroup. The odds ratio for breast tumours occurring before 50 in < or =55 MM/CFA families was 3.71. We also observed increased numbers of liver cancers, CSU and leukaemias. OF and EF analyses revealed increased risk of occurrence of cancers of breast (OF 10.4%, EF 4.5%) and liver (OF 1.9%, EF 0.8%) in women from MM/CFA families, RR for breast tumours was approximately 3.3 in < or =55 MM/CFA families. Molecular examination of MM/CFA families revealed no alterations within the BRCA2 gene and one germline mutation of the BRCA1 gene. In conclusion, it seems to be justified to consider systematic breast surveillance beginning at the age around 35-40 years as an option in women from < or =55 MM/CFA families.