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

• Main Author: Dębniak Tadeusz
• Format: Article
• Language: English
• Published: BMC 2007-06-01
• Series: Hereditary Cancer in Clinical Practice
• Subjects: CDKN2A; ARF; XPD; MC1R; melanoma; breast cancer; family history; age at diagnosis; cancer risk; mutation analysis; Poland
• Online Access: http://www.hccpjournal.com/content/5/2/97

<p>Abstract</p> <p>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. <it>CDKN2A</it>, 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 <it>XPD </it>and <it>MC1R</it>. We studied <it>CDKN2A/ARF</it>, <it>XPD </it>and <it>MC1R </it>for their associations with melanoma and breast cancer risk in Polish patients and controls. We found that <it>CDKN2A </it>and <it>ARF </it>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 <it>CDKN2A </it>gene A148T, previously regarded as non-pathogenic, may predispose to malignant melanoma, early-onset breast cancer and lung cancer. Compound carriers of common <it>XPD </it>variants may be at slightly increased risk of breast cancer or late–onset malignant melanoma. Common recurrent variants of the <it>MC1R </it>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 <it>CDKN2A</it>, <it>XPD </it>or <it>MC1R </it>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.</p>