Some Molecular and Clinical Aspects of Genetic Predisposition to Malignant Melanoma and Tumours of Various Site of Origin

Based on epidemiological data we can assume that at least some malignant melanoma (MM) and breast cancer cases can be caused by the same genetic factors. CDKN2A, which encodes the p16 protein, a cyclin-dependent kinase inhibitor suppressing cell proliferation, is regarded as a major melanoma susceptibility gene and the literature has also implicated this gene in predisposition to breast cancer. Genes also known to predispose to MM include XPD and MC1R. This paper reviews a range of studies which have been performed in Polish populations with the following objectives:1. Assessment of the risk of malignancies of various sites of origin in relatives of malignant melanoma patients from families with strong familial cancer aggregation.2. Assessment of germline mutation and large deletion analysis of the CDKN2A/ARF genes in families with multiple melanomas and in families with an aggregation of malignant melanoma and breast cancer.3. Determination of the association of CDKN2A common variants with melanoma risk.4. Assessment of breast cancer risk among carriers of the common CDKN2A variants.5. Assessment of clinical characteristics of CDKN2A-positive breast cancers in young women.6. Assessment of CDKN2A common variants and multi-organ cancer risk.7. Assessment of XPD common variants and their association with melanoma and breast cancer risk. 8. Assessment of MC1R common variants, CDKN2A and their association with melanoma and breast cancer risk.(based on Debniak T, Gorski B, Cybulski C, Jakubowska A, Kurzawski G, Kladny J, Zaluga E, Fiedorowicz J, Debniak B, Lubinski J. Increased risk of breast cancer in relatives of malignant melanoma patients from families with strong cancer familial aggregation. Eur J Cancer Prev 2003; 12: 241–245)Population screening for familial aggregation of malignancies performed recently by our centre for the West Pomeranian region of Poland (population 1.5 m) has shown that among families with strong aggregation of tumours the most frequently dia