CDKN2A Mutation and Higher Nevus Count Can Increase Risk for Subsequent Primary Melanoma

There is a high certainty of evidence that patients with CDKN2A mutation and a moderate or high nevus count had significantly increased risk for multiple primary melanomas, according to study results published in the British Journal of Dermatology.

Researchers conducted a systematic review and meta-analysis to identify specific risk factors for developing subsequent primary melanoma. They searched 4 databases (CINAHL, CENTRAL, EMBASE, and MEDLINE) for studies published between 1982 and August 2022. A total of 27 studies with 388,424 patients were included in their analysis.

The researchers found that men were at higher risk for subsequent primary melanoma than women (low certainty of evidence; hazard ratio [HR], 1.46; 95% CI, 1.40-1.53), as were older patients (moderate certainty of evidence; HR, 1.19; 95% CI, 1.14-1.24). In addition, compared with a low/moderate family history of melanoma, a strong family history was found to greatly increase the risk of developing subsequent melanoma (low certainty of evidence; odds ratio [OR], 1.79).

Factors with the highest certainty of evidence of increased risk for multiple primary melanomas included CDKN2A mutation and moderate or high nevus count (ORs 5.29, 1.64, and 2.63, respectively). Other factors included lentigo maligna/lentigo maligna melanoma or ‘other’ melanoma subtype vs superficial spreading melanoma (HR 1.16 and 1.14, respectively), presence of at least 1 atypical nevus (OR, 3.01), light skin color (HR, 1.44), first lesions occurring on the head or neck, and inadequate sun protection (HR, 1.85).

Neither hair color (blonde or red hair vs dark hair) nor eye color (blue eyes vs dark eyes) was a significant factor associated with the risk for subsequent primary melanoma. Breslow thickness (2.01-4 mm vs in situ and >4 mm vs in situ) was not associated with increased risk for subsequent primary melanoma. There were mixed findings regarding the impact of in situ vs invasive primary melanoma on the risk for developing subsequent primary melanoma.

The researchers concluded, “Better estimates of personal risk and improved risk stratification can assist with tailoring surveillance, guiding the use of total body photography, and patient education.” They added, “It may also improve quality of life by reducing anxiety about developing melanoma. Additionally, the ability to stratify risk and responsibly allocate scarce health and financial resources is an important public health consideration.”