V. Who Else In My Family Is at Risk for Developing Melanoma?

• Hair color, eye color, and skin color are determined by genetics.

• People with blond or red hair, a fair complexion, and/or numerous freckles have a higher lifetime risk of developing melanoma than those individuals with a darker phenotype (darker skin, hair, and eyes).

• Those lighter phenotype individuals tend to burn easily and do not tan.

Interview With the Experts:

Dr. David Fisher discussing on how melanin impacts our hair color, eye color and skin colors. Most importantly, how melanin impact the risk of skin cancer

Dr. David Fisher discusses the physiology behind why and how we get tanned after UV exposure.

• Studies have shown that men tend to have higher risk then woman.

• The higher incidence rate of melanoma seen in men can be attributed to the fact that men usually do not protect themselves from the UV exposure. In addition, men do not like to use sunscreens.

• People over the age of 60 years old appear to have a higher risk. As we age, we accumulate DNA damage in the cells, resulting in higher incidence of cancers of all types.

• Individuals with a history of intense and intermittent UV exposure are at a high lifetime risk of developing melanoma.

• The UV exposure can come from the sun or from artificial sources such as tanning booths.

• Both UVB and UVA can cause damage to the DNA in the cells.

• Individuals with a history of blistering or multiple sunburns, especially at an early age, have significantly higher risks for developing melanoma in adulthood.

• Individuals with a personal history or family history of melanoma are at higher risk for developing melanoma.

• Individuals with many atypical (dysplastic) moles (nevi) have a higher risk.

• Compared to the risk in the general public, the risk of developing melanomas for individuals with many moles (more than 50) is 7 to 54 times higher.

• Individuals with some atypical moles but no personal or family history of melanomas are 7 to 27 times more likely to develop melanoma than people in the general population.

• Persons with a combination of atypical moles, prior personal history of melanoma, and a family history of melanoma have 500 times higher risk than that of the general public.

• If you have melanoma, please tell your immediate blood-relatives (e.g., children, siblings, and parents. This does not apply to your in-laws) that they should have at least a baseline skin examination. By telling them, you may save the life of someone you love.

Interview With the Experts:

Dr. Allan Halpern discusses the development of nevi or moles in kids and other risk factors.

• Individuals with actinic keratoses (a type of pre-skin cancer), and non-melanoma skin cancers (e.g., basal cell and squamous cell cancers) are also at a higher risk for developing melanoma.

• All of these skin cancers are associated with increased UV exposure from the sun and other artificial light sources.

• Individuals with “giant” congenital moles have a higher risk of developing melanoma than the general public (congenital means “at birth”).

• “Giant” congenital moles are defined as moles that are larger than 20 cm in diameter in an adulthood (they grow as the body grows).

• An individual who was born with a large congenital mole generally should be monitored closely by his or her health care providers for signs of melanoma.

• The immune system plays an important role in detecting and destroying melanomas.

• Patients with a suppressed immune system have a higher risk for developing melanoma.

• Those individuals include patients who are solid organ (e.g., kidney, heart or liver) or hematopoietic (bone marrow) transplant recipients. Transplant patients are required to take immune suppression drugs to prevent organ rejections.

• Other immune suppressed individuals include patients with HIV infections.

Genetic makeup plays a major role in determine the risk of developing melanoma.

Understand key terminologies:

• Germline mutations are passed on from your parents, and these mutations occur in the DNA of the egg or sperm cells. These set of mutations affect all the cells in your body, and can be passed on to your children.

• Somatic mutations occur in non-reproductive cells in the body. These cells make up the tissue and organs in the body, but not the eggs or sperms that form the zygote (the first cell formed by the union of the egg and sperm). These mutations occur later in life, and we acquire them sporadically as we age. These mutations are not passed on to your offspring.

• Oncogene is a gene that activates the growth and division of cells.

• Tumor suppressor gene functions to slow the growth and division of cells.

• Mutation in either oncogenes and tumor suppressor genes can lead to the development of cancer.

Interview With the Expert:

Dr. Sancy Leachman discusses germline and somatic mutations.

Important genes that play a role in the development of melanoma.

• MC1R gene (melanocortin 1 receptor). MC1R plays a role in the production of melanin, the pigment that gives color to the skin, hair, and eyes.

• CDKN2A (cyclin-dependent kinase inhibitor 2A). This is a tumor suppressor gene that helps to regulate cell growth and division.

• PTEN (phosphatase and tensin homolog), another tumor suppressor gene that helps to regulate cell growth and division.

• BAP1 (BRCA1-associated protein 1), another tumor suppressor gene that is located at chromosome 3p21.3. The BAP1 protein is involved in DNA repair, cell growth, and cell death.

• BRCA1 (breast cancer 1, early onset), another tumor suppressor gene that is located on chromosome 17q21. The BRCA1 protein functions in DNA repair and cell cycle regulation.

Interview With the Expert:

Dr. Sancy Leachman discusses the various types of mutations and genetic counseling starting from minute 1:20.