Risk Factors For The Development Of Malignant Melanoma Skin Cancer
Our skin owes its color to haemoglobin content of the blood (in both oxygenated and reduced state), carotenoids and melanin pigment present in it.
The major color determinant melanin, is produced by special star shaped cells, the melanocytes present in the upper layer or epidermis of skin. Each epidermal melanocyte is surrounded by a group of 36 keratinocytes or the skin surface cells, with which it maintains functional contact and supplies melanin filled packets called melanosomes to them, the whole being an epidermal melanin unit.
Melanocytes are found in nearly every organ in our body, but they are most common in epidermis and dermis of skin, hair follicles, eye, around blood vessels, nerves, in the lining of coelomic cavity (our body cavity in which major organs like intestines, liver, pancreas and kidneys are placed), leptomeninges (membranes covering vital structures of our nervous system) and inner ear.
In certain genetically predisposed individuals these pigment forming melanocytes are stimulated by certain environmental factors, and they undergo rapid, uncontrolled multiplication to develop a malignancy or cancer named malignant melanoma (malignant means cancerous; melanoma, tumor of melanocytes).
A unique feature of melanoma is that visual inspection is the surveillance tool leading to earlier detection and a better outcome.
The chances of melanoma development can be significantly reduced by modifying environmental risk factors for which public awareness needs to be created.
The various risk factors that contribute to the development of this cancer include the following :
Sun exposure triggers melanoma
Ultra violet radiation is a major cause of melanoma in fair skinned population and plays a major role in increasing the incidence of this cancer.
Melanoma mainly develops at sites exposed to sunlight with sparing of consistently covered areas. It develops not on the areas of maximum sun exposure, but on areas that are intermittently exposed.
In males, the trunk, particularly the upper back is the most common site, while in females both lower legs and upper back are the common sites of affliction.
Long term sun exposure increases risk of head and neck melanomas.
Younger migrants to sunny climates have an increased risk for melanoma as compared with adult migrants.
Children who sustain frequent, severe sunburns before age 12 years have a 3.6 elevated risk of developing melanoma. Sunburns even within 10 years preceding the diagnosis of melanoma also lead to a two fold increase in risk.
Melanoma also follows a "latitude gradient" that is, ultraviolet radiation is stronger in areas near the equator, thus risk of melanoma is also higher.The risk of melanoma reduces as the distance from equator increases, higher the latitude, lower is the risk. Thus melanoma risk is higher in places like Australia and the Mediterranean region as compared to European countries and Canada. Such places receive long hours of sunlight.
Cutaneous melanoma is more likely to occur in fair skinned individuals than in dark skinned people living within similar geographic region. This is because the melanin content in dark skinned individuals is protective against solar radiation. It causes the skin to tan, reducing the severity of sunburns and also there are fewer moles or naevi on the dark skin, that may serve as precursor lesions of melanoma.
According to International journal of Cancer the typical melanoma patient is an indoor office worker who is not exposed to regular daily sunlight but who enjoys one or two holidays every year at sunny locations that receive high intensity ultra violet radiation.
Therapeutic exposure to psoralens, the medicine frequently prescribed for vitiligo and psoriasis, and subsequent exposure to ultra violet-A radiation (PUVA therapy) as in PUVA chambers also increases the risk of developing melanoma.
Reaction of skin to sunlight
The risk of melanoma increases with a tendency to sunburn on exposure to intense ultra violet radiation and little or no tendency to tan with long term exposure.
Occupation and social status
Melanoma risk is increased in higher socioeconomic status group, might be due to a greater leisure time and tendency to take vacations in sunny locations.
Familial melanoma has an incidence of 10-15% amongst all the cases of melanoma. If you have at least two of your first degree relatives with melanoma, your risk of developing this cancer is significantly increased.
Familial melanoma develops at an early age, is almost always associated with multiple primary lesions and dysplastic naevi. These naevi are markers for individuals at increased risk of melanoma. Dysplastic naevi appear like common moles but pathologically have architectural and cellular abnormalities similar to that of a melanoma.
Persons with familial melanoma have better chances of survival than their non-familial counterparts because of higher awareness about the disease and have thinner tumors on an average at the time of diagnosis.
A deletion or a mutation of the familial melanoma gene located on chromosome 9, that has been documented in approximately 40% of such patients. Familial atypical mole melanoma syndrome, the BK mole syndrome and the dysplastic naevus syndrome are all associated with familial cases of melanoma.
According to the British Medical Journal, light colored skin, fair or red hair, blue or green eyes, freckling and ease of sunburn make a person more susceptible to melanoma risk.
Risk factors of cutaneous melanoma
1. Pigmentary changes
- Blue eyes.
- Fair or red hair
- Light complexion.
2. Response to sun exposure
- Freckling tendency.
- Inability to tan.
- Tendency to sunburn.
3. Upper socioeconomic status.
4. Family history of melanoma.
5. p16 Mutation (genetic linkage)
- Melanocytic naevi or common moles
- Dysplastic naevi
- Changing mole
- Congenital naevus
7. Prior history of melanoma
Melanocytic naevi or moles
Congenital melanocytic naevi are brown or black pigmented patches present since birth , that may darken, enlarge and develop terminal hair over a period of years.
Acquired melanocytic naevi or the common moles are flat or slightly raised pigmented stubs, varying from 1 mm to 1 cm in size that develop from multiplication of melanocytes at the interface between dermis and epidermis of the skin.
Both types of moles bear a potential risk to transform into a melanoma, though the chances are very low. Approximately one-third of all melanomas are associated with a naevus remnant.
Presence of atypical moles or dysplastic naevi in individuals with a family history of melanoma is a substantial risk factor.
Presence of a solitary atypical mole doubles the risk of melanoma developing, while having 10 or more atypical naevi is associated with a 12-fold increased risk.
Risk of melanoma progression also increases in proportion with the number of common moles, both present since birth or acquired later, with the presence of 50 to 99 small moles (<15 mm size) or more than 10 large moles (>15 mm size) doubling the chances of melanoma.
Factors that increase melanoma risk
Intermittent intense sun exposure
Two or more first degree relatives with melanoma
Migration to areas with strong sun
Ease of sunburn
Presence of atypical moles
Past history of melanoma
Freckling increases melanoma risk
Gender and Hormonal factors
Melanoma is rare before puberty, with the risk increasing from second decade onwards. The mean age at presentation is early in the sixth decade with a slight female preponderance.
Long term use of oral contraceptives over a period of 10 years or more leads to an increased risk of melanoma. The cancer also worsens during pregnancy.
Obesity can put you at a risk of developing this cancer as per a study detailed in American journal of Epidemiology.
Smoking does not appear to increase the risk of developing a melanoma, but worsens the course of a pre-existing one.
Melanoma can also spread through placenta from an affected mother to her fetus.
Individuals with a very low body immunity are more susceptible to the development of melanoma. People suffering from Addison's disease(reduced function of adrenal glands leading to a deficiency of steroid hormone cortisol in the body) are particularly at risk.
Comprising less than 5% of all skin cancers, but mostly associated with a rapid downhill course and carrying a grim prognosis, malignant melanoma is one of the most dreaded skin condition.
Predominantly seen in fair skinned individuals, red hair, pronounced freckling on the upper back, blistering sunburns and outdoor jobs in teen years and a family history of melanoma increase the chances of developing this condition.
Sunlight, especially intermittent exposure to intense sun in indoor workers plays a key role.