Primary prevention of melanoma

INTRODUCTION — Melanoma is a worldwide public health concern [1-3]. At least two-thirds of melanoma in populations with lightly pigmented skin worldwide may be attributed to ultraviolet (UV) radiation exposure from both natural and artificial sources [4]. Based upon this and other data implicating UV light as a risk factor for melanoma, reducing exposure to UV radiation from sunbathing and indoor tanning and increasing the use of sun protection has been advocated as a method to reduce the incidence of this malignancy [4,5]. Based on findings from SunSmart, an Australian skin cancer prevention program, the United States Centers for Disease Control and Prevention (CDC) estimated that a comprehensive national skin cancer prevention program focused on the avoidance of UV radiation exposure from sunbathing and indoor tanning could avert 230,000 melanoma cases and USD $2.7 billion in initial year treatment costs from 2020 to 2030 [6].

The observed decline in the incidence of invasive melanoma in the state of Queensland, Australia, among males and females under the age of 40 years from the period of 1995 to 2014 may be the result of sun awareness campaigns implemented in Australia on a national scale [7,8]. A similar reduction in melanoma incidence in younger males and females (age ≤45) was observed in the United States from the period of 2005 to 2014 [9]. Whether this reduction is related to increased sun protection behaviors, decreased intentional tanning, or reduced use of tanning beds among adolescents and young adults remains unclear [9,10].

Interventions that may be relevant to the primary prevention of melanoma will be reviewed here. Screening and risk factors for melanoma are discussed separately. (See "Screening for melanoma in adults and adolescents" and "Melanoma: Epidemiology and risk factors".)

ULTRAVIOLET RADIATION — Ultraviolet (UV) radiation is a known carcinogen [11]. Although a direct causal relationship between UV radiation and melanoma has not been demonstrated in humans, there is strong evidence in support of this relationship:

●Epidemiologic studies have found that the risk of melanoma is higher among people with lightly pigmented skin who have increased sensitivity to sunlight [5]. In the United States, the incidence of melanoma is at least 20 times greater in White persons than in Black persons, and the highest incidence of melanoma worldwide occurs in Queensland, Australia, a subtropical region with a predominantly Celtic population [12]. (See "Melanoma: Epidemiology and risk factors", section on 'Geographic and ethnic variation'.)

●A study aimed at quantifying the global population attributable fraction of melanomas due to UV radiation estimated that 168,000 new melanoma cases in 2012 were attributed to excess exposure to UV radiation, representing approximately 76 percent of all melanoma cases worldwide [13]. The global burden was higher in men than in women (95,000 attributable cases; 81.3 percent of all melanomas and 73,000; 69.4 percent, respectively). The World Health Organization (WHO) data estimated that excessive UV radiation exposure caused approximately 325,000 melanomas and 57,000 premature melanoma-related deaths in the year 2020 [14].

●Among families predisposed to melanoma because of genetic mutations, the incidence of melanoma is 21-fold higher for individuals born after 1959 compared with those born before 1900, presumably due to an interaction between increased sun exposure and the predisposing gene mutation [15]. (See "Inherited susceptibility to melanoma".)

●In the laboratory, melanocytic lesions, including melanoma, can be induced in human skin grafted onto mice after exposure to ultraviolet B (UVB) radiation, with or without an initiating carcinogen [16].

●Other data implicate ultraviolet A (UVA) radiation as well as UVB as contributors to melanoma development. Psoriasis patients treated over long periods with a combination of UVA and oral psoralen (PUVA) had a significant increase in melanoma incidence [17,18]. (See "Melanoma: Epidemiology and risk factors", section on 'Psoralen plus ultraviolet A therapy'.)

●Several systematic reviews and meta-analyses of case-control studies found an approximately 20 percent increase of melanoma risk among ever users of indoor tanning devices compared with nonusers [19-21]. The risk was higher for individuals reporting first use of sunbeds at a young age (before age 35) and for those with high exposure (≥10 sessions in lifetime). (See 'Tanning bed use' below and "Melanoma: Epidemiology and risk factors", section on 'Indoor tanning'.)

●One population-based cohort study using data from the Norwegian Women and Cancer Study and including more than 140,000 women followed up for a mean of 14 years found that the risk of melanoma was increased by 25 percent among women reporting ever use of indoor tanning versus never use and was higher for those who initiated indoor tanning use before the age of 30 years [22]. The risk increased with increasing duration of use (≥10 years) and cumulative number of indoor tanning sessions (relative risk 1.61, 95% CI 1.27-2.05 for the highest quartile of cumulative number of sessions).

The exact pathways through which UV radiation can cause melanoma are incompletely understood. Two different, "divergent" epigenetic pathways that can result in cutaneous melanoma are suggested by epidemiologic population-based data [23]. Individuals with an inherently low propensity for melanocyte proliferation may require chronic sun exposure to drive clonal expansion. In contrast, those with a high propensity for melanocyte proliferation (characterized by high nevus count) may require less solar exposure to stimulate carcinogenesis [23]. (See "Melanoma: Epidemiology and risk factors", section on 'Common (typical) nevi'.)

Unlike keratinocytes, which undergo apoptosis (programmed cell death) when severely damaged by UV radiation, damaged melanocytes tend to be preserved [24]. This may be related to an effort by the body to continue to produce melanin, which has a photoprotective function in the skin [5]. The result, however, is that severely damaged melanocytes that are at risk for incomplete deoxyribonucleic acid (DNA) repair and subsequent mutation are preserved. UVB radiation (290 to 320 nm) causes the majority of DNA damage in the epidermis. However, UVA may also be important in the pathogenesis of melanoma [25]. (See "Melanoma: Epidemiology and risk factors", section on 'Ultraviolet radiation'.)

The pattern and timing of exposure to sunlight appear to be important for melanoma development. In contrast to nonmelanoma skin cancers (particularly squamous cell carcinoma), which are associated with cumulative sun exposure and occur most frequently in areas maximally exposed to the sun (ie, the face, back of hands, and forearms), most melanomas are associated with intense, intermittent sun exposure and tend to occur in areas exposed to the sun sporadically (eg, the back, lower legs) [26,27].

Exposure in childhood seems particularly important; a history of five or more severe sunburns in adolescence more than doubles the risk of developing melanoma [28]. Furthermore, the incidence of melanoma is increased among people who migrated from northern to more equatorial latitudes but only among immigrants who were children at the time of migration [29,30]. (See "Melanoma: Epidemiology and risk factors", section on 'Ultraviolet radiation'.)

SUN PROTECTION — The classification of ultraviolet (UV) radiation as carcinogenic to humans and a risk factor for melanoma and other skin cancers is used to support recommendations for sun protection [11]. Since people with darkly pigmented skin have significantly lower risk of UV radiation-induced skin cancer compared with those with lightly pigmented skin, sun protection recommendations may differ according to skin phenotype [31-33].

Sun protection behaviors include the use of broad-spectrum sunscreen with a sun protection factor (SPF) of 15 for everyday use and at least SPF 30 for intense sun exposure; wearing hats, sunglasses, and sun-protective clothing; reducing sun exposure; seeking shade during midday hours (10 AM to 4 PM); and avoiding indoor tanning bed use [34]. (See "Selection of sunscreen and sun-protective measures".)

Sunscreen — Individuals at increased risk of melanoma and individuals highly exposed to sunlight should thoroughly apply a broad-spectrum sunscreen (with an SPF of 15 for daily use and at least an SPF of 30 for intense sun exposure) before going out during daylight hours. Because of inconsistent application, the American Academy of Dermatology recommends the use of a broad-spectrum sunscreen with an SPF of at least 30 during sun exposure.

●Efficacy – A systematic review for the US Preventive Services Task Force (USPSTF) in 2018 noted that although interventions focused on increasing sun protection behavior (eg, reduced sun exposure, sunscreen use, use of protective clothing, avoidance of indoor tanning) were associated with a moderate increase of sun protection behaviors in both adults and children, there was no consistent association between these interventions and reduced sunburn frequency, nevus count, or skin cancer incidence over one to three years of follow-up [35]. However, data from a follow-up study of a community-based, randomized trial in Queensland, Australia, a Norwegian population-based cohort study, and an Australian case-control study support the use of sunscreen products [36]:

•In the Australian trial, 1621 participants were randomly assigned to an intervention group (unlimited supply of SPF 16 sunscreen provided and participants instructed to engage in daily sunscreen use) or a discretionary sunscreen group (participants used their own sunscreen at their own discretion) [36]. Ten years after the conclusion of the four-year trial, participants in the intervention group had developed 50 percent fewer primary melanomas compared with the control group (11 versus 22 melanomas, hazard ratio [HR] 0.50, 95% CI 0.24-1.02). The reduction was even greater for invasive melanomas: 3 melanomas occurred in the intervention group versus 11 in the control group (HR 0.27, 95% CI 0.08-0.97), corresponding to a risk reduction of 73 percent. Young and middle-aged adult participants in the intervention group were also 24 percent less likely to show findings of skin photoaging. This study provides strong evidence that the regular use of sunscreen reduces the incidence of melanoma in high-risk populations. In addition, in the same trial the rates of squamous cell carcinomas were decreased by nearly 40 percent during the entire follow-up period (rate ratio 0.62, 95% CI 0.38-0.99) [37].

•A prospective population-based cohort study using data from the Norwegian Women and Cancer Study and including nearly 144,000 women aged 40 to 75 years followed up for a mean of 11 years found that the risk of melanoma was reduced by approximately 30 percent (HR 0.67, 95% CI 0.53-0.83) among women using SPF ≥15 sunscreen on at least one occasion compared with nonusers or those consistently using SPF <15 [38]. The estimated population attributable fraction (ie, the proportion of preventable melanomas) associated with SPF ≥15 sunscreen use was 18 percent. Of note, in this study, sunscreen users were more likely to be in the youngest age groups; live in areas with high ambient UV radiation; have lightly pigmented skin; and report more sunburns, sunbathing vacations, and indoor tanning, suggesting that the results might underestimate the protective impact of sunscreen use in this population.

•An Australian case-control study including 603 melanoma cases and 1088 controls aged 18 to 39 years examined the association between sunscreen use during childhood and lifetime sunscreen use and risk of melanoma before the age of 40 years [39]. In a multivariate analysis, self-reported childhood sunscreen use and lifetime sunscreen use were both associated with a lower risk of melanoma (odds ratio [OR] for the highest versus the lowest tertile 0.6, 95% CI 0.42-0.87 and OR 0.65, 95% CI 0.45-0.93, respectively), after adjusting for age, sex, ethnicity, education, family history, nevus density, sun bed use, blistering sunburns, total sun exposure, and pigmentation score.

●Labeling, use, and safety – Labeling and regulations, proper use, and safety of sunscreens are discussed separately. (See "Selection of sunscreen and sun-protective measures".)

Other measures — In addition to use of sunscreen products, other approaches may also be useful to decrease exposure to UV light, including:

●Wearing clothes – Tightly woven fabrics and dark colors confer the highest UV protection. In addition, sun-protective clothes with designed ultraviolet protection factor (UPF) ranging from 15 to 50 are commercially available and can also be worn while swimming. Since sunscreen may not be applied as thoroughly or often as needed, sun-protective clothing is an effective alternative. (See "Selection of sunscreen and sun-protective measures", section on 'Photoprotective clothing'.)

●Using special window glass and films – Common window glass provides a variable degree of ultraviolet B (UVB) protection. Developments in the glass industry have resulted in the introduction of additional filters for ultraviolet A (UVA) and infrared radiation [40]. Window films that can be applied to side windows of cars are also commercially available. These films should be compliant with state regulations in the United States or national regulations in other countries.

●Using sunscreen-containing cosmetics – Cosmetics and moisturizers for daily use that contain broad-spectrum sunscreens with SPF ≥15 may improve the compliance to photoprotection [41].

In the United States, the Skin Cancer Foundation has developed a list of products, including cosmetics, moisturizers, clothes and laundry additives, sunglasses, and window protection, that can provide sun protection.

Sun protection and nevi — The presence of atypical nevi or high numbers of common nevi has been associated with increased risk for melanoma. Although sun-protective measures in children have been linked with the development of fewer nevi [42,43], it remains unclear whether sun protection can reduce the risk for melanoma through this pathway [44]. (See "Melanoma: Epidemiology and risk factors", section on 'Common (typical) nevi' and "Melanoma: Epidemiology and risk factors", section on 'Atypical nevi'.)

The following studies support the effect of sun protection on reductions in nevi count:

●Sunscreen use has been shown to modestly attenuate the development of new moles in young children. In a randomized trial, White schoolchildren were randomly assigned to receive either SPF 30 broad-spectrum sunscreen (with instructions to apply it if sun exposure was expected to last 30 minutes or longer) or to no intervention [43]. Children in the sunscreen group developed fewer nevi over a three-year period (median count 24 versus 28, without sunscreen). The use of sunscreen was especially beneficial for freckled children in the intervention group. These children developed 30 to 40 percent fewer nevi than those in the control group.

●At least two studies suggest that the use of a physical barrier (clothing) to prevent sun exposure may be of value for reducing the number of nevi. In one report of 12-year-old children who had been followed for more than six years, those who covered their backs all of the time had fewer new nevi than children who covered their backs less than 70 percent of the time [45].

●Another study found that children who wore more clothing during holidays in sunny climates developed fewer nevi [46]. Multivariate analysis in this study did not demonstrate a benefit from the use of sunscreen.

Additional studies are necessary to determine the relationship between sun protection, nevi count, and risk of melanoma.

General guidelines — Several guidelines have been developed by scientific and specialty groups for protection from exposure to the sun [47-53]. The National Council on Skin Cancer Prevention, which is comprised of more than 40 skin cancer organizations and foundations in the United States, provides comprehensive information on skin cancer prevention that can be summarized as follows [54-56]:

●Avoid sun burning, intentional tanning, and using tanning beds.

●Wear sun-protective clothing, a wide-brimmed hat, and sunglasses. Seek shade.

●Use extra caution near water, snow, and sand.

●Get vitamin D safely through food and vitamin D supplements.

●Choose a sunscreen that offers an SPF of 30 or higher, is water resistant, and provides broad-spectrum coverage (protects against UVA and UVB rays).

●Apply sunscreen approximately 15 minutes before going outside.

●Reapply sunscreen every two hours or after swimming or sweating, according to the product labeling.

●Apply a generous amount.

The 2014 Surgeon General's Call to Action to Prevent Skin Cancer presents the following five strategic goals to support skin cancer prevention in the United States:

●Increase opportunities for sun protection in outdoor settings

●Provide individuals with the information they need to make informed, healthy choices about UV radiation exposure

●Promote policies that advance the national goal of preventing skin cancer

●Reduce harms from indoor tanning

●Strengthen research, surveillance, monitoring, and evaluation related to skin cancer prevention

Status of sun protection — Participation in sun-protective measures has varied over time and with population demographics. Examples of data on sunburn and use of sun protection include the following:

●In a United States cross-sectional study using a nationally representative sample of over 31,000 adults from the 2015 National Health Interview Survey (NHIS)-Cancer Control Supplement, 34 percent of participants experienced sunburn in 2015 [57]. The most frequently used sun protection behaviors were staying in the shade (37 percent) and using sunscreen (32 percent), followed by wearing long clothing to the ankles (28 percent).

●In a large population-based study using data from the Norwegian Women and Cancer Study and including nearly 149,000 women aged 41 to 75 years, 87 percent reported sunscreen use during bathing vacations in southern latitudes [58]. From 1997 to 2007, the overall sunscreen use increased, although this was not accompanied by a decrease in the sunburn rate, with 39 percent of women reporting at least one sunburn in the previous year in 1997 and 46 percent in 2007.

●More than 28,000 adults participated in the 2005 NHIS and were asked questions regarding sun protection behaviors and sunburns in the past year. Sun protection practices were weakest among youngest adults, persons residing in the Midwest, males, non-Hispanic White persons, those who were less educated, smokers, risky drinkers, and individuals that had skin that was less sun sensitive [59]. A 2010 analysis of the NHIS data on nearly 25,000 adult Americans found an overall sunburn rate of 37 percent in the past year, with highest rates among youngest adults of 18 to 29 years (52 percent) [60]. Rates of ≥44 percent were found among individuals who repeatedly burn or freckle after two weeks in the sun, White persons, indoor tanners, and those with a family history of melanoma.

●In a series of more than 10,000 children of nurses from the Nurses' Health Study, only 34 percent of children aged 11 to 18 were using sunscreen, and 83 percent had at least one sunburn during the previous summer [61].

Observational studies have noted deficits in shade seeking and covering up among all age groups [62]. Protective practices appear to be more prevalent at the beach or on vacation than in other outdoor recreation [63]. Parents/caregivers are more likely to protect their children than themselves, although they often do not provide adequate protection for their children. One randomized trial that investigated the impact of mother education on sun protection for their children found that, taken together, 22 and 54 percent of children in the intervention and control groups, respectively, experienced a sunburn or tan during their first and second summers of life [64]. Likewise, a study of Swedish toddlers found that 20 percent had been severely sunburned at least once before their first birthday [65]. Persons with lightly pigmented skin, higher education, more knowledge, a greater fear of skin cancer, females, and those who know someone with skin cancer generally practice more preventive habits.

Perceived social norms appear especially important among adolescents and young adults. Positive attitudes toward tanning (ie, healthy, attractive) predict a lower use of sun protection [66]. Young teens' practice of sun protection tends to modestly decrease as peer pressure and fashion concerns start to influence their behavior. In a prospective study involving 360 fifth-grade children, 50 percent of students reported "often or always" use of sunscreen when outside for at least six hours in the summer [67]. At the follow-up evaluation three years later, this proportion dropped to 25 percent. At the same time, more children reported "liking a tan" and spending time in the sun to get a tan.

Vitamin D deficiency — Strict sun protection can increase the risk for vitamin D deficiency. Oral vitamin D supplementation is a safe, well-tolerated, and inexpensive alternative to achieve adequate vitamin D levels [68-70]. (See "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment" and "Vitamin D insufficiency and deficiency in children and adolescents".)

TANNING BED USE — The working group of the International Agency for Research on Cancer concluded that tanning bed use in youth was associated with skin cancer and documented a 75 percent increase in melanoma for those who first used tanning beds in their twenties or teen years [71]. Based upon these findings, the working group concluded that minors and young adults should avoid the use of tanning devices and supported restricting access to artificial tanning facilities for individuals under the age of 18 [72].

Increased risk for melanoma has also been detected in individuals who begin tanning in mid-adulthood [73]. A population-based, case-control study including 681 patients with melanoma and 654 matched controls younger than 50 years found that women who had ever tanned indoors had a two- to sixfold increased risk of melanoma compared with women who had never tanned indoors, with the highest risk observed among those who were younger than 30 years at diagnosis [74]. In all age groups, the risk was consistently increased for women who started tanning indoors before age 25 years and for those who reported >10 lifetime tanning sessions.

●Indoor tanning ban for minors – In Europe, individuals under the age of 18 years are banned from using tanning beds in France, Spain, Belgium, Germany, the United Kingdom, Denmark, Finland, Iceland, Norway, Sweden, and Lithuania [75]. In Canada, tanning beds are banned for those under the age of 18 in Ontario, Quebec, and British Columbia and under the age of 19 in Nova Scotia [76]. In 2008, a joint Australian and New Zealand solarium standard banned the use of sun tanning units for persons under 18 years and for all persons with skin type I [77]. From January 2015, tanning beds have been banned in the Australian Capital Territory, New South Wales, Queensland, South Australia, Tasmania, and Victoria. A similar ban was introduced in Brazil in 2009.

In the United States, indoor tanning is banned for those under 18 in California, Connecticut, Delaware, the District of Columbia, Hawaii, Illinois, Kansas, Louisiana, Maine, Massachusetts, Minnesota, Nevada, New Hampshire, New York, North Carolina, Ohio, Oklahoma, Oregon, Rhode Island, Texas, Utah, Vermont, Washington, and West Virginia; in many other states, permission from parents/legal guardians is required for minors [78]. Studies aimed at assessing the tanning facility compliance to state laws banning indoor tanning use before the age of 18 years found that approximately 80 percent of tanning facilities are compliant [79,80].

In May 2014, the US Food and Drug Administration (FDA) issued an order requiring that sunlamp products used in tanning salons carry a visible boxed warning that states that sunlamp products should not be used on persons under the age of 18 years [81].

●Addiction to tanning – Tanning bed users have reported relaxation [82], pain relief [83,84], and improved mood [85] as motivation for continuing this practice, and there is increasing evidence that biochemical addiction to tanning can occur [86-89]. In a survey of 3874 high school adolescents, 7 percent met the criteria for tanning addiction [90]. In multivariable analysis, tanning addiction had a weak association with problematic substance use and psychologic symptoms, such as depressive symptoms, panic disorder symptoms, and obsessive-compulsive disorder symptoms. However, further studies are necessary to determine the relationship between tanning and psychiatric disorders and the best approach to patients who exhibit signs of a tanning addiction. In the interim, clinicians should remain cognizant that psychologic factors may play a role in the reluctance or inability of some patients to stop tanning.

The mechanism for an addiction to tanning is unconfirmed. It has been proposed that ultraviolet (UV)-induced production of pro-opiomelanocortin products, including beta endorphins, may be a contributing factor. This theory was supported by the findings of a small randomized trial in which opioid blockade with naltrexone was associated with a reduced preference of UV exposure among frequent tanners [91]. Administration of naltrexone also led to withdrawal symptoms in four out of eight frequent tanners, while no infrequent tanners experienced withdrawal-like symptoms. However, the relationship between tanning bed exposure and opioid production remains controversial [92].

CHEMOPREVENTION — Chemoprevention (also called therapeutic prevention) is defined as the use of natural or synthetic agents to delay, reverse, suppress, or prevent premalignant lesions from progressing to invasive cancer and has been evaluated in melanoma and other skin cancers as a means of primary prevention [93-95]. Various phytochemicals, vitamins, minerals, and anti-inflammatory, antioxidant, and targeted agents are being studied, though none has been proven to prevent melanoma in clinical trials to date [96].

Vitamin D — Sun exposure is necessary for the synthesis of 25-hydroxyvitamin D in the skin. This intermediate metabolite is transformed to its biologically active form under conditions of physiologic demand for calcium and phosphorus. The potential health benefits of vitamin D continue to be explored as the incidence and survival of major internal cancers is known to improve significantly with decreasing latitudes in the United States [97]. The antiproliferative and proapoptotic effects of active vitamin D (ie, 1,25-dihydroxyvitamin D) may be a factor in the association of vitamin D with lower risk for some malignancies. (See "Overview of cancer prevention", section on 'Vitamin D'.)

Serum levels of vitamin D — An effect of vitamin D on melanoma pathogenesis was suggested by a case control study of 500 melanoma patients in which sun exposure, as measured by solar elastosis, was associated with increased survival [98]. However, serum vitamin D levels were not assessed in this study, and vitamin D levels are unlikely to be the only reason for this observation, particularly given "diverging" ultraviolet (UV) radiation-associated, phenotypic, and genetic pathways of melanoma development [23]. A 2014 meta-analysis of 20 observational studies including 1420 melanoma patients did not find an association between serum levels of vitamin D and risk of melanoma [99].

Dietary vitamin D — Studies investigating the impact of dietary vitamin D on the risk of melanoma have shown conflicting results:

●Although in vitro and in vivo mouse studies have suggested a protective effect of vitamin D on melanoma [100-105], a prospective cohort study involving 68,611 patients found no association between vitamin D intake and the occurrence of melanoma [106]. An earlier case-control study found no association of melanoma risk with total vitamin D intake [107].

●At least two studies of dietary vitamin D and melanoma risk have resulted in other conclusions. A case-control study of more than 1000 subjects identified a significant reduction of melanoma risk for individuals with high vitamin D intake [108]. Conversely, a large prospective study reported an increased risk of melanoma associated with cod liver oil intake (a source of vitamin D) among women but not men [109].

●A 2014 meta-analysis of 20 observational studies including 1420 melanoma patients did not find an association between dietary intake of vitamin D and risk of melanoma [99]. The pooled relative risk for the highest versus lowest quintile of vitamin D intake was 0.86 (95% CI 0.63-1.13).

●Calcium plus vitamin D supplementation did not reduce the overall incidence of melanoma or nonmelanoma skin cancer (NMSC) in postmenopausal women in the Women's Health Initiative (WHI) (hazard ratio [HR] 0.86, 95% CI 0.64-1.16) [110]. However, in a subgroup analysis of participants who reported a history of NMSC, women in the vitamin D and calcium group had 57 percent fewer melanomas than women in the placebo group (HR 0.43, 95% CI 0.21-0.90). This finding suggests a role for either vitamin D or calcium, or their combination, in reducing the incidence of melanoma in a high-risk group of postmenopausal women.

Nonsteroidal anti-inflammatory agents — Nonsteroidal anti-inflammatory agents (NSAIDs) have been suggested as having chemopreventive effects against melanoma. However, observational studies of different medications and in different populations have provided inconsistent evidence [111].

Several case-control studies have found a protective effect of acetylsalicylic acid (ASA) and other NSAIDs [112-114]. The melanoma risk reduction ranged from 13 to 50 percent, depending upon the frequency and duration of use. The risk reduction was greatest for long-term, continuous use of low-dose ASA [112,113]. A reduced risk of melanoma among ASA users was also observed in the WHI Observational Study, a large cohort study including 59,806 postmenopausal women [115]. In this study, the risk of melanoma was 21 percent lower in women using ASA than in nonusers (HR 0.79, 95% CI 0.63-0.98) [115]. In contrast, another large cohort study including 63,809 patients did not find any association between NSAID use and melanoma risk [116].

Lipid-lowering agents — Lipid-lowering drugs, such as statins and fibrates, have also been evaluated. Three systematic reviews and meta-analyses of randomized trials of statins and fibrates for the prevention of heart disease were unable to identify a statistically significant effect of lipid-lowering drugs on melanoma risk [95,117,118].

Other promising agents — In a randomized phase 3 trial, the use of oral nicotinamide (vitamin B3) 500 mg twice daily for 12 months resulted in a 13 percent reduction of actinic keratoses (p = 0.001) and a 23 percent reduction of NMSCs (p = 0.02) [119]. However, the study was not adequately powered to assess an effect on melanoma and was conducted over a relatively short period of time, making it difficult to determine whether nicotinamide might be a good candidate for melanoma prevention. Given the shared UV radiation-related etiology of these tumors, further investigation appears warranted.

Other candidate agents for therapeutic prevention of melanoma include pigmentation enhancers, DNA repair enzymes, additional vitamins and minerals, and phytochemicals (ie, plant-derived, biologically active compounds) [120].

PUBLIC HEALTH MEASURES — A variety of public health measures have been implemented in an attempt to reduce the risk of skin cancers, including melanoma. Examples include government-sponsored efforts, such as the SunSmart campaign in Australia and the Environmental Protection Agency's SunWise Program in the United States. The media is another outlet for increasing awareness of sun protection; some television stations and newspapers notify the public of days on which the risk of high ultraviolet (UV) exposure is elevated. However, no studies have directly linked the implementation of public health programs to a reduction in melanoma incidence.

Clinician efforts to educate patients on protection from UV light exposure may influence patient behavior. A 2011 systematic review performed for the US Preventive Services Task Force (USPSTF) found that patient counseling with tailored feedback in the primary care setting was associated with modest improvement in sun-protective practices and reduced indoor tanning [121]. A 2018 update of this review confirmed small to moderate effects of behavioral interventions on increased sun protection behaviors in all age groups, with more consistent effects seen in children and adolescents [35]. Based on evidence of benefit of behavioral counseling interventions on children's parents, adolescents, and young adults, the USPSTF recommends counseling young adults, adolescents, children, and parents of young children about minimizing exposure to UV radiation for persons aged 6 months to 24 years with fair skin type to reduce their risk of skin cancer [122]. Based on evidence of the limited net benefit of counseling all adults older than 24 years, the USPSTF also recommends that clinicians consider selectively offering counseling to adults older than 24 years with fair skin type based on their risk factors.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Melanoma screening, prevention, diagnosis, and management".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Sunburn (The Basics)")

●Beyond the Basics topics (see "Patient education: Sunburn (Beyond the Basics)" and "Patient education: Sunburn prevention (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Reducing exposure to ultraviolet radiation – Ultraviolet (UV) radiation has been implicated as a risk factor for melanoma. Although studies of the impact of UV-protective measures on melanoma incidence are limited, interventions to reduce individual exposure to UV light are recommended, especially in people with lightly pigmented skin. (See 'Ultraviolet radiation' above.)

Shade structures, sun-protective clothing, sunscreen, and other measures can provide sun protection. Individuals at increased risk of melanoma and individuals highly exposed to sunlight should apply a broad-spectrum sunscreen with a sun protection factor (SPF) of 15 or higher daily and thoroughly before going out during daylight hours. Because of inconsistent application, the American Academy of Dermatology recommends the use of a broad-spectrum sunscreen with an SPF of at least 30 before sun exposure. (See 'Sun protection' above and "Selection of sunscreen and sun-protective measures".)

●Avoiding indoor tanning – Tanning bed use is associated with an increased risk for melanoma and should be avoided. Additional studies are necessary to explore whether some individuals develop a biochemical addiction to tanning. (See 'Tanning bed use' above.)

●Chemoprevention – There is limited and conflicting evidence that vitamin D, nonsteroidal anti-inflammatory agents, or lipid-lowering agents have a chemopreventive effect on melanoma. Other agents are under investigation for therapeutic prevention of melanoma and nonmelanoma skin cancer. (See 'Chemoprevention' above.)

●Public health measures – A variety of public health programs, most notably the Australian SunSmart campaign, have resulted in improved sun protection as well as stabilization of incidence rates that were increasing precipitously in earlier years. The US Preventive Services Task Force (USPSTF) recommends counseling young adults, adolescents, children, and parents of young children about minimizing exposure to UV radiation for persons aged 6 months to 24 years with fair skin type to reduce their risk of skin cancer and selectively offering this counseling to people over the age of 24 years with fair skin type based on their risk factors. (See 'Public health measures' above.)