Cancer begins when one or more genes change from their normal form. This either creates an abnormal protein or no protein at all, both of which cause mutated cells to multiply uncontrollably. (Association, 2011) Melanoma can either be caused by inherited genes or defects that are caused from environmental factors, such as exposure to too much sun. However, according to the Centre for Genetics Education, all cancers can be considered genetic in origin because they arise from changes in the normal cancer protection genes that we all have.
(Education, 2007) What Genetic mutations produce the greatest risk of skin cancer? Are these gene mutations germ-line (passed from parent to child), or caused by exposure to UV light? The most common gene mutations in melanoma is CDKN2A, these genes are an automatic controller of cell division. CDKN2A can be inherited or non-inherited. Mutations in these regulators of cell division are the most common causes of inherited melanoma. These mutations, however, are still very uncommon overall and can also appear in non-inherited cases of melanoma.
People with this gene often have a large number of irregularly shaped moles and are diagnosed with melanoma at a young age. (Association, 2011) GENETIC MUTATIONS THAT CAUSE SKIN CANCER 3 CDK4 and CDK6 have important roles in progression of cells from G1 to S phase. CDK4 and CDK6 partner with the family of proteins that control the progression of cells through the cell cycle by activating cycling dependent kinases enzymes (a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP to specific substrates).
Phosphorylation of the retinoblastoma releases transcription factors, inducing gene expression and metabolic changes that precede DNA replication, thus allowing the cell to progress through the cell cycle. These genes are significant because they are in the same signaling pathway as CDKN2A. CDK4 can be passed on by parent, but germ-line is rear. CDK6 have not been identified as a gene mutation germ-line. (Association, 2011) MDM2 – The MDM2 genetic variant appears in the gene’s “promoter,” a kind of power switch that determines when the gene is turned on and how many copies are produced within a cell.
It predisposes women, but not men, to develop melanoma at a younger age (less than 50 years old). Having this mutation may be even more potent than other melanoma risk factors such as a history of blistering sunburns, fair skin, and freckling. (Education, 2007) What gene(s) control the color of skin, hair, and eyes? Genes involved with skin pigment that have been identified as having an increase in susceptibility to melanoma include; MC1R – the greater the number of variations in this gene the greater the risk for melanoma.
This gene plays an important role in GENETIC MUTATIONS THAT CAUSE SKIN CANCER 4 determining if a person has red hair, fair skin, and sensitivity to UV radiation. People who have olive and darker skin and who carry one or more variations of the gene have a higher than average risk for melanoma. Other genes involved with skin pigment that also increase’s susceptibility to melanoma are TYR (tyrosinase), TYRP1 (TYR related protein 1), and ASIP (agouti signalling protein). (Association, 2011) What genetic mutations produce the greatest risk of skin cancer?
Are these gene mutations germ-line (passed from parent to child) or caused by exposure to UV light? Gene mutations that aren’t inherited but are acquired due to environmental factors such as the sun include: BRAF – This gene is a non-inherited mutation in the BRAF gene. It is the most common reason for melanoma. P16-P16 is a tumor suppressive gene that may be abnormal in some non-inherited cases of melanoma. EGF – EGF makes a substance called epidermal growth factor (EGF). EGF plays a role in skin cell growth and wound healing, and it may account for many non-inherited cases of melanoma.
Fas – Fas is a mutation in genes that regulate Fas proteins, which are involved in a natural process of cell self-destruction called apoptosis which can cause melanoma cells to proliferate out of control. (Education, 2007) GENETIC MUTATIONS THAT CAUSE SKIN CANCER 5 What recommendation about UV light exposure would be made to individuals who are genetically susceptible to skin cancer? If you understand cancer genes and how the play a part in melanoma, skin cancer, it may help you understand the risk factors and what you can do about it.
Minimally, people at risk for hereditary melanoma should practice sun safety and examine their skin carefully each month beginning at age 10 to look for changes in the appearance of moles. When out in the sun, these people should wear a broad spectrum sunscreen with a protection factor between 15 and 30, however try to avoid the sun between the hours of 10am to 4pm, when the sun’s rays are the strongest. Genetic testing allows for results in predisposed people, but testing will not help whether or not you get melanoma nor can they stop melanoma from developing if you are predisposed. (Education, 2007).