Abstract
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. We studied CDKN2A/ARF, XPD and MC1R for their associations with melanoma and breast cancer risk in Polish patients and controls. We found that CDKN2A and ARF do not contribute significantly to either familial melanoma or malignant melanoma within the context of a cancer familial aggregation of disease with breast cancer. However, the common variant of the CDKN2A gene A148T, previously regarded as non-pathogenic, may predispose to malignant melanoma, early-onset breast cancer and lung cancer. Compound carriers of common XPD variants may be at slightly increased risk of breast cancer or late–onset malignant melanoma. Common recurrent variants of the MC1R gene (V60L, R151C, R163Q and R160W) may predispose to malignant melanoma. In general, the establishment of surveillance protocols proposed as an option for carriers of common alterations in CDKN2A, XPD or MC1R variants requires additional studies. It is possible that missense variants of genes for which truncating mutations are clearly pathogenic may also be deleterious, but with reduced penetrance. This may be overlooked unless large numbers of patients and controls are studied. A registry that includes 2000 consecutive breast cancer cases, 3500 early onset breast cancer patients, 500 unselected malignant melanoma and over 700 colorectal cancer patients has been established in the International Hereditary Cancer Centre and can contribute to these types of large association studies.
Highlights
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
We examined 3 groups of families: group 1 (FMM cases), MM probands from 16 families with at least 2 first-degree relatives affected with MM registered at the Hereditary Cancer Centre in Szczecin; group 2 (44 cases), probands diagnosed with MM and having at least 2 first-degree relatives, one affected with breast cancer and the other diagnosed with either breast cancer or a malignancy at a different site; group 3 (22 cases), family defined by the index patient being diagnosed with breast cancer, a first-degree relative with melanoma and a family history of at least one more first-degree relative affected by any malignancy
We have shown that the A148T allele of the CDKN2A gene is overrepresented in a population of 3318 unselected patients with breast cancer under age 50, and in 891 unselected patients with breast cancer at age 50 and above
Summary
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 implicated this gene in predisposition to breast cancer. This paper reviews a range of studies which have been performed in Polish populations with the following objectives: Hereditary Cancer in Clinical Practice 2007; 5(2). 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
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