Risk factors for melanoma

In this article, we will go through the main risk factors and give the shortest and most succinct explanation about each of them.
According to the American organization NCCN (National Comprehensive Cancer Network), the main risk factors for the development of melanoma are:
1) Male, age over 60 years

On closer examination, everything turned out to be much more complicated than the statement that "men suffer from melanoma more often than women." The incidence of melanoma in men over 50 years old is indeed higher. However, women are more likely to get sick before this age.

Some researchers explain this by the fact that young women visit the solarium with greater frequency than men. The connection with pregnancy and the birth of children has not been confirmed. At the same time, for women who gave birth to their first child after 30 years, the risk of melanoma is 10% higher [1].

Unfortunately, assumptions about why the overall risk of getting melanoma throughout life in men is 1.5 times higher than in women could not be found. [1]

Regarding the age, there were such statistics. The bulk of the authors write that at the age of 60 there is a peak in the incidence of melanoma in men.
2) Syndrome of multiple dysplastic (atypical) nevi

In two large meta-analyses (summarizing the results of a large number of studies), it was noted that the risk of melanoma increases in direct proportion to the number of atypical pigmented nevi.

What is atypical nevus? This is when the entire nevus or part of it is represented as a spot, and also have three of the five signs:

– fuzzy border;
– size 5 mm or more;
– different colors;
– uneven contour;
– redness of the skin.

A person with 5 atypical nevi has a 6-fold higher risk of developing melanoma than someone who does not have them. [3].

You can read more about atypical nevi here.
3) The presence of a large number of nevi on the skin

Here we note that the number of moles is not the case: "if there are few moles, then there is no risk" – it is, just lower than with a large number of moles. According to the same meta–analysis as in the previous paragraph [3] - the danger increases in direct proportion to the number of moles.
4) Hypersensitivity of the skin to sunlight, a tendency to rapid burning in the sun. Red hair, blue eyes (the first phototype of skin on the Fitzpatrick scale)

We have combined these two features in one subtitle, since they practically do not occur separately.
Everything is simple here – people with the first phototype have more pheomelanin pigment in their skin, which has weaker protective properties than eumelanin. As a result, the effect of sunlight becomes more destructive for the body of these people. It is enough for a person with such skin to stay in the sun without sunscreen for a short time to get serious burns.[4]
5) Multiple sunburns, sunburns to blisters

Proven facts about sunburn and melanoma that you need to know.
  • To burn once according to the scenario: "burned, the skin turned red, ached and peeled off" – it's not scary. I am sure that everyone who reads this article remembers such a burn.
  • It is worse to get such burns regularly.
  • The most dangerous option is burns to blisters, especially repeated and, especially, at the age of 15 to 20 years.
  • For the development of melanoma, short-term and intense UV exposure is more important ("badly burned on vacation") than less strong and stretched over time ("worked as an asphalt paver for 20 years").
  • It doesn't matter when a person got burned to blisters – 30 years ago or last summer, the risk will be increased for life. [5]
6) Precancerous and cancerous skin diseases: actinic keratosis, basal cell carcinoma, squamous cell skin cancer, oncological diseases in childhood

The presence of the diseases listed in the subtitle indicates that a person has already been exposed to sunlight. Consequently, the DNA of melanocytes is already damaged and has less resistance to mutations. Such cells are more likely to become precursors of melanoma.

Can different types of skin cancer appear simultaneously or with an interval? Can. Moreover, if one malignant tumor has already developed on the skin, the likelihood of other types of cancer, including melanoma, will be increased. [6]

Oncological diseases in childhood (bone sarcoma, leukemia, lymphoma, central nervous system tumor, Wilms tumor and neuroblastoma) may be associated with an increased risk of melanoma. [11]


7) Taking drugs that suppress immunity associated with organ transplantation, bone marrow (we are talking mainly about glucocorticoids).

Patients who have undergone organ transplantation are forced to take glucocorticoid hormones for a long time. This is necessary for moderate suppression of immunity. Otherwise, the transplanted organ will be rejected, because an autoimmune reaction will develop. Such therapy has another unpleasant effect – the risk of melanoma increases. Melanoma in such patients proceeds more aggressively with a lower 5-year survival rate. [7]

The question "to accept or not to accept", unfortunately, is not worth it in this situation. Rejection of the transplanted organ means death for the patient faster than the possible development of melanoma in the future.


8) Immunodeficiency associated with HIV or other factors (for example, hepatitis B and C)

Here the explanation is the same as in the previous paragraph – problems with immunity are directly related to an increased risk of developing melanoma. [8]


9) Rare hereditary skin diseases, for example, xeroderma pigmentosa

The life expectancy of patients with pigmented xeroderma does not exceed, as a rule, 20 years. This disease is characterized by the appearance of spots on the skin resembling freckles, which gradually increase and merge. In addition, there are other hormonal disorders and degenerative changes in the nervous system. Melanoma develops in such patients in the vast majority of cases. [9]


10) Genetic predisposition (CDKN2A, CDK4, MC1R polymorphisms). Melanoma in blood relatives of the first line of kinship

Regarding genetic predisposition, it is important to note that the detection of mutations in these genes does not always mean a 100% chance of getting melanoma. In addition, such changes may be associated with pancreatic cancer. [10]


11) Frequent visits to the solarium

A study by Dean Lazovich and co-authors proved that if the total amount of time spent in a solarium during a lifetime exceeds 50 hours, then the risk of melanoma can be increased by 3 (!!!) times.
When spent in a solarium from 1 to 9 hours – the risk of developing melanoma increases by 46%, from 10 to 19 hours – by 81% (!!!)

Separately, we note that the risk increases in comparable proportions both in tanning salons with UV-A and UV-B rays.
"
Regular visits to the solarium for a long time increases the risk of getting melanoma. This is a universally recognized fact!
12) Accommodation in southern countries or in mountainous areas.

Periodic or episodic strong exposure to ultraviolet radiation, for example, during seasonal work or during vacations in southern regions
The higher the terrain is above sea level, the less UV rays detain the ozone layer of the atmosphere and the greater the risk of getting burned by a person in this area. The same situation is with proximity to the equator – the closer, the more intense the UV exposure and more dangerous.

Also recall that snow is a particular danger in the mountains – it can reflect up to 80% of UV rays.


13) Chronic exposure to ultraviolet radiation

We are talking about those whose work is connected with staying in the sun. Builders, agricultural workers, road workers and people of other professions associated with regular prolonged exposure to ultraviolet radiation. They need to protect their skin with overalls and special creams, nothing else has been invented yet.
I have a risk factor! What to do?

The first and most important thing is to put aside the panic. If there is a risk factor, this does not mean that melanoma will develop 100%. The presence of one or more risk factors just means that you need to pay more attention to the simple rules of prevention of melanoma:

1. Avoid prolonged exposure to the sun from 10 to 16 hours. If you stay in the sun for a long time before 10 and after 16, be sure to apply SPF-50 sunscreen to all exposed skin areas. Never go to the solarium.

2. When removing any skin formations on a broad basis, it is mandatory to require a histological examination.

3. Complete self-examination of the skin with mapping should be carried out 1 time in 6 months with the rules of ABCDE, "ugly duckling". In our NOTA mole tracker app, you will be able to record important information about your points, as well as track the dynamics of changes, if there is one.

4. Examination of the ENTIRE skin by an oncologist with dermatoscopy should take place 1 time a year.
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List of literature

1) Kurtis B. Reed, Jerry D. Brewer, Christine M. Lohse, Kariline E. Bringe, Crystal N. Pruitt, and Lawrence E. Gibson. Increasing Incidence of Melanoma Among Young Adults: An Epidemiological Study in Olmsted County, Minnesota.


2) Gandini S, Sera F, Cattaruzza MS, et al. Meta–analysis of risk factors for cutaneous melanoma: I. Common and atypical naevi. Eur J Cancer. 2005; 41:28–44. [PubMed: 15617989]


3) Olsen CM, Carroll HJ, Whiteman DC. Estimating the attributable fraction for cancer: A metaanalysis of nevi and melanoma. Cancer Prev Res (Phila). 2010; 3:233–245. [PubMed: 20086181]


4) Mitra D1, Luo X, Morgan A, Wang J, Hoang MP, Lo J, Guerrero CR, Lennerz JK, Mihm MC, Wargo JA, Robinson KC, Devi SP, Vanover JC, D'Orazio JA, McMahon M, Bosenberg MW, Haigis KM, Haber DA, Wang Y, Fisher DE. An ultraviolet–radiation–independent pathway to melanoma carcinogenesis in the red hair/fair skin background. Nature. 2012 Nov 15;491(7424):449–53. doi: 10.1038/nature11624. Epub 2012 Oct 31.


5) Wu S, Han J, Laden F, Qureshi AA. Long–term ultraviolet flux, other potential risk factors, and skin cancer risk: a cohort study Cancer Epidemiol Biomarkers Prev. 2014 Jun;23(6):1080–9. doi: 10.1158/1055–9965.EPI–13–0821.


6) Wheless L, Black J, Alberg AJ. Nonmelanoma skin cancer and the risk of second primary cancers: a systematic review. Cancer Epidemiol Biomarkers Prev. 2010 Jul;19(7):1686–95. doi: 10.1158/1055–9965.EPI–10–0243. Epub 2010 Jun 22.


7) Vajdic CM, Chong AH, Kelly PJ, Meagher NS, Van Leeuwen MT, Grulich AE, Webster AC.

Survival after cutaneous melanoma in kidney transplant recipients: a population–based matched cohort study. Am J Transplant. 2014 Jun;14(6):1368–75. doi: 10.1111/ajt.12716. Epub 2014 Apr 14.


8) Risk of melanoma in people with HIV/AIDS in the pre– and post–HAART eras: a systematic review and meta–analysis of cohort studies. Olsen CM, Knight LL, Green AC. PLoS One. 2014 Apr 16;9(4):e95096. doi: 10.1371/journal.pone.0095096. eCollection 2014. Review.


9) Kraemer KH, Lee MM, Scotto J. Xeroderma pigmentosum. Cutaneous, ocular, and neurologic abnormalities in 830 published cases. Arch Dermatol. 1987 Feb;123(2):241–50.


10) Udayakumar D, Tsao H. Melanoma genetics: an update on risk–associated genes. Hematol Oncol Clin North Am. 2009; 23:415–429. vii. [PubMed: 19464594] Authors review genes of variable risk implicated in CMM, most notably CDKN2A.


11) Pappo AS, Armstrong GT, Liu W, et al. Melanoma as a subsequent neoplasm in adult survivors of childhood cancer: A report from the childhood cancer survivor study. Pediatr Blood Cancer. 2012


12) Indoor tanning and risk of melanoma: a case–control study in a highly exposed population.

Lazovich D1, Vogel RI, Berwick M, Weinstock MA, Anderson KE, Warshaw EM. Cancer Epidemiol Biomarkers Prev. 2010 Jun;19(6):1557–68. doi: 10.1158/1055–9965.EPI–09–1249. Epub 2010 May 26.