Melanoma epidemiology and staging progress

Melanoma is one of the malignant tumors with the fastest increasing incidence in recent years, with an annual growth rate of about 3 to 5 percent. According to statistics, the number of new melanoma cases and deaths in 2010 is expected to be 199,627 and 46,372 respectively. The number of melanoma cases accounts for about 1.6 percent of the global new cancer cases and the number of deaths accounts for about 0.6 percent of the world.

Epidemiological status worldwide

In developed countries, melanoma is a common malignant tumor with an estimated age-standardized annual incidence of 9/100,000, while in underdeveloped regions this figure is only 0.6/100,000; the corresponding mortality rates are 1.4/100,000 and 0.3/100,000, respectively. The mortality-incidence ratios of the two are 0.16 and 0.50, respectively, suggesting that the survival of patients in underdeveloped regions after being diagnosed with melanoma is significantly worse than that of melanoma patients in developed regions.

From a geographical perspective, the regions with the highest melanoma incidence in the world are Australia and New Zealand. According to statistics from the World Health Organization, the estimated age-standardized incidence of melanoma in the region was 36.6/100,000 in 2008. Among them, Queensland, Australia, is the region with the highest incidence of melanoma in the world, with incidence rates of 55.8/100,000 and 41.1/100,000 for men and women, respectively.

The annual incidence rates of melanoma following Australia and New Zealand are (age-standardized rate): North America (13.9/100 000), Northern Europe (12.7/100 000), Western Europe (11.2/100 000), Southern Europe (6.5/100 000), Southern Africa (5.6/100 000), Central and Eastern Europe (4.3/100 000), etc.

Areas with high melanoma incidence also have higher mortality rates. As incidence increases, the mortality-to-incidence ratio decreases. Therefore, in areas with high incidence, survival is expected to be better.

Although the overall incidence of melanoma in my country is not high, the huge population base in my country has kept the absolute number of melanoma cases high. With the continuous improvement of diagnostic technology and methods, the incidence of melanoma in my country has also been increasing year by year, which is particularly evident in large cities in China. According to statistics from Shanghai, the incidence of melanoma in Shanghai was 0.2/100,000 men and 0.3/100,000 women in 1995, while in 2005 it reached 0.5/100,000 and 0.4/100,000 respectively. According to data from Beijing, the incidence of melanoma in Beijing was 0.3/100,000 men and 0.2/100,000 women in 1998, while it rose to 0.8/100,000 and 0.5/100,000 in 2004.

Risk factors

(I) Ultraviolet radiation

The main risk factor for melanoma is ultraviolet radiation. Both UVA and UVB bands of ultraviolet rays can cause harm to the human body and induce the occurrence of melanoma, but the specific mechanism is not clear.

Sunlight exposure

Elwood JM et al. summarized the literature on risk factors for skin melanoma and found that intermittent sunlight exposure and sunburn history were positively correlated with the incidence of melanoma (OR=1.71), while high-continuous sunlight exposure was negatively correlated with the incidence of melanoma (OR=0.86), suggesting that acute sunlight exposure-induced skin sunburn is more important than chronic cumulative sunlight exposure in the incidence of melanoma. Many reports indicate that chronic cumulative sunlight exposure in children and adolescents has a more serious impact on the incidence of melanoma than adults.

Artificial UV radiation

Indoor UV exposure is becoming increasingly prevalent in developed countries, especially in Northern Europe and the United States. People who are exposed to indoor UV radiation before the age of 30 have a 75% higher risk of developing melanoma than those who are not exposed to indoor UV radiation.

(II) Epigenetic factors

The meta-analysis results show that people with light skin (especially those with light hair such as red or blonde, light eyes such as blue or green, and those who are easily sunburned), people with multiple melanocytic nevi, people with melanocytic dysplasia nevi and atypical nevus syndrome, and people with family members who have had melanoma are all at high risk of melanoma.

(III) Familial hereditary melanoma

About 10% of melanoma patients have a family history of melanoma; those whose first-degree relatives have melanoma have a melanoma incidence rate that is twice as high as that of the general population. This increased risk of melanoma may be related to the same light skin color and sun exposure habits among family members, but another important factor is hereditary gene changes. CDKN2A and CDK4 genes are two melanoma susceptibility genes that have been identified, and their mutations may lead to an increased risk of melanoma.

(IV) Other factors

Age and gender

In the European and American populations, the incidence rates of males and females almost increase in parallel around middle age, but with increasing age, the difference in incidence rates between males and females gradually increases. By the time of old age, the incidence rate of males is significantly higher than that of females. The reason for this difference is still unclear, and it may also be related to ultraviolet exposure. However, in Asian countries, including my country, this difference does not seem to be obvious.

Socioeconomic status

Melanoma rates tend to be higher in people with higher socioeconomic status (job, education, income, and living environment), but the difference appears to be smaller in developed countries.

Race

Compared with South American, African, Middle Eastern, and Asian people, Europeans have a much higher incidence of melanoma. Studies have shown that this difference in incidence persists even when these ethnically diverse groups live in the same city, suggesting that the difference in incidence is determined by genetic characteristics rather than environmental differences.

Molecular epidemiology

Unlike Caucasians, the primary lesions of melanoma in yellow and black people are mostly located in the heels, palms, toes, and under the nails, which are rarely exposed to ultraviolet radiation. This also suggests that the incidence of melanoma in the latter may not be related to ultraviolet radiation. Gene mutation may play an important role in this.

A specific genetic change that has been found to play a role in melanoma is the mutation of the BRAF gene. Mutations at the V600E site account for more than 90% of BRAF gene mutations in melanoma. Most BRAF gene mutations are somatic mutations, presumably induced by environmental factors. BRAF gene mutations are common in non-chronic sun-damaged (non-CSD) skin melanomas (about 70%), while the frequency of BRAF gene mutations is lower in chronic sun-induced damage (CSD) skin melanomas (only about 15%). Other gene mutations, including NRAS, c-KIT, AKT, and recently GANQ, have been found in melanoma patients.

Melanoma staging and progression

The current staging of cutaneous malignant melanoma adopts the 7th edition of the AJCC staging system in 2010. This staging system basically retains the TNM staging standard in the 6th edition, with the only change being that in the T1 stage, the original "Clark classification" is replaced by "mitotic rate ≥ 1/mm2" as the standard for diagnosing the T1b stage. The reason is that the multivariate Cox regression model established using the updated 2008 AJCC melanoma database clearly reflects that in patients with a tumor thickness of 0.5 to 1 mm, the mitotic rate is the main prognostic factor, while in contrast, the invasion level is not statistically significant.