You may have noticed after reading my previous post on melanoma that I am a big sunscreen advocate. This is, in part, because melanoma is the most common and deadly form of skin cancer. It is generally accepted that UV exposure is the main culprit behind melanoma incidence, but there may be more to the melanoma story.

Among those 20-40 years in age, the incidence of melanoma in women is much greater than in men. Only in the age group of 50-80 years do the incidence rates for men surpass women. Until recently, the reason for increased incidence of melanoma in young women was unknown.

Researchers in the laboratory of Dr. David Polsky at NYU Langone Medical center may have found the missing link to the incidence paradox. Published this week in the journal Clinical Cancer Research, Polsky’s group found that women in the 20-40 year age group with a single nucleotide polymorphism (SNP) at position 309 in the P2 promoter of the MDM2 gene (MDM2 SNP309) exhibited a nearly four fold (3.89) greater risk of being diagnosed with melanoma than women without the SNP. Additionally, the median age for diagnosis of melanoma was 13 years earlier in women with the MDM2 SNP309 genotype. In contrast, the median age of diagnosis in men did not differ in those with MDM2 SNP309. This association is consistent with other findings, as MDM2 SNP309 has been associated with various cancers in young women.

The researchers hypothesize the discrepancy between men and women may be due to estrogen signaling. The estrogen receptor activates the transcription factor Sp1. Previous in vitro studies demonstrate that MDM2 SNP309 increases the binding affinity of Sp1 to the MDM2 promoter region, upregulating MDM2 expression. Because MDM2 is a negative regulator of the tumor suppressor p53, the increased activation of MDM2 in those with MDM2 SNP309 may result in an increased incidence of cancer. This hypothesis also explains why incidence rates of melanoma decrease once women approach menopausal age (average age of menopause is about 51 years).

Even though your should still follow the American Cancer Society’s prevention guidelines in order to help protect yourself from skin cancer, this work is an important step in identifying additional risk factors for developing melanoma.

Firoz, E., Warycha, M., Zakrzewski, J., Pollens, D., Wang, G., Shapiro, R., Berman, R., Pavlick, A., Manga, P., Ostrer, H., Celebi, J., Kamino, H., Darvishian, F., Rolnitzky, L., Goldberg, J., Osman, I., & Polsky, D. (2009). Association of MDM2 SNP309, Age of Onset, and Gender in Cutaneous Melanoma Clinical Cancer Research, 15 (7), 2573-2580 DOI: 10.1158/1078-0432.CCR-08-2678