Melanoma emerges through the malignant alteration of melanocytes. If diagnosed early, the disease is treatable. Studies have shown that an earlier diagnosis improves the prognosis for 90–95% of patients. The AnteMEL test is a novel approach to the assessment of individual melanoma risk based on a combination of polygenic risk score, mutations in high-risk susceptibility genes and lifestyle risk factors. This test specifies personal risks and gives individualised recommendations for clinical management and individualised screening.
Who can benefit from the AnteMEL test?
This test is suitable for men and women aged 25–80 who have European ancestry.
How frequent is melanoma?
Cutaneous melanoma has the highest mortality rate among common skin cancers, and its incidence is rising worldwide. It thus represents a significant health care burden and is considered the most lethal form of skin cancer if not detected and treated during its early stages. Melanoma incidence in EU28 can reach up to 90,000 new cases per year, and it is considered one of the fastest-growing cancer forms. The risk of melanoma rises with age and the average age at diagnosis is about 60. With an aging population, the number of melanoma cases will likely remain high for the foreseeable future. Melanoma is about 1.5 times more frequent in men than it is in women.
The genetics behind melanoma
Genetic factors play a major role in the development of melanoma. Improvements in genetics have led to the identification of new genetic variants that affect one’s susceptibility to melanoma.
At about 58%, the heritability rate of melanoma is one of the highest among types of cancer. Approximately 5–10% of melanoma cases are related to the familial context, which means that genetic factors greatly influence the risk. Susceptibility for some families is due to mutations in some of the known melanoma predisposition genes: CDKN2A, MC1R, CDK4, TP53, PTEN, BAP1, POT1, ACD, PARK2, TERF2IP and TERT. Specifically, the cyclin-dependent kinase inhibitor 2a (CDKN2A) gene accounts for up to 20–45% of hereditary melanoma cases.
Genome-wide association studies (GWAS) have identified dozens of individual genetic loci associated with melanoma. Some of these loci are located near genes related to pigmentation or associated with the nevus count. The melanoma risk prediction scores are calculated from these SNPs to distinguish people in higher genetic risk groups. The combined genetic risk score is associated with increased melanoma incidence and is clinically relevant.
What are other risk factors for melanoma?
The aetiology of melanoma is complex and interconnected with several environmental risk factors. Family and previous personal history of melanoma both contribute to the risk of melanoma and its recurrence. The most significant environmental risk factor is solar ultraviolet radiation exposure, but susceptibility to melanoma has also been associated with the increased presence of atypical nevi, skin, hair and eye pigmentation and individual tanning habits.
Melanoma prevention and early detection
Current methods for melanoma detection and screening consist in large part of a visual full-body skin inspection by a medical professional. The medical professional asks about the patient’s family history of melanoma, other medical conditions, treatment methods and exposure to sources of natural and artificial UV radiation. Early detection of melanoma is critical in order to treat pre-cancerous conditions, to prevent the development of the condition and to improve the general prognosis.
Novel detection methods can improve early melanoma diagnoses. AnteMEL is a predictive genetic test for individual risk of melanoma. It seeks to consider all risk factors in order to provide careful pre-tumour management and prevention recommendations.
AnteMEL will be available in the second half of 2019.