Nonmelanoma Skin Cancer in Young Women

The incidence of nonmelanoma skin cancer (NMSC) has been reported to be increasing rapidly over the past few decades, with an estimated 2 million cases diagnosed annually.^1-3 Composed largely of both basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), these tumors typically develop in older adults as a result of excessive lifetime ultraviolet (UV) exposure.⁴ More recently, studies have reported a dramatic increase in the incidence among the young population— particularly women younger than 40 years.^5-7 Speculations for this increase include varying sun exposure practices, changes in clothing trends, increased indoor tanning, and heightened awareness and surveillance. While few studies to date have investigated the risk factors for this unique population directly, many studies have observed parallel trends that provide indirect evidence supporting these claims.

In this paper, we highlight the rising incidence of NMSC in young women, review the pathogenesis of NMSC, comment on possible risk factors for early development of these tumors, and discuss strategies for prevention.

Recent studies have demonstrated an increasing incidence of NMSC in women younger than 40 years. Christenson et al⁵ found a statistically significant increase in the incidence of BCCs in women, but not in men, younger than 40 years during 1976 to 2003. The authors also noted an increase in the incidence of SCC, although this trend was significant for both men and women. Another study conducted in Denmark found that between 1978 and 2007, women had a higher average annual percentage incidence change for both BCC and SCC compared with men.⁶ In particular, the average annual percentage change in BCC incidence among women younger than 40 years was significantly higher (6.0%) compared with those older than 40 years (4.51%). Additional data obtained from a retrospective analysis of a middle-south Italian population from 1994 to 2003 demonstrated a 56.5% increase in the number of BCC cases for patients younger than 35 years compared with a 26.6% increase for patients over 35.⁷ In the younger age group, there was a slightly higher female to male ratio (1.17:1) compared with the general population (1.04:1).

Interestingly, these studies have also noted an increase in BCCs on the trunk among young females. The exact etiology remains to be elucidated, however, some authors have speculated that excessive tanning bed use⁸ and accumulated intense, intermittent UV exposure may be the cause of this observation.^5,9

The major environmental risk factor for the development of NMSC is exposure to UV radiation. While both UVB and UVA have been shown to cause DNA damage in the skin resulting in carcinogenesis, their mechanisms of action are different. UVB causes direct DNA damage by inducing the formation of cyclobutane pyrimidine dimers resulting in C→T and CC→TT mutations.¹⁰ DNA damage due to UVA occurs indirectly through the formation of reactive oxygen species.¹¹ Under normal circumstances,upregulation of tumor suppressor genes can mediate the DNA damage by initiating DNA repair, cell cycle arrest, and apoptosis of damaged keratinocytes. Accumulation of sufficient numbers of DNA mutations, including those that disable tumor suppressor genes, can result in formation of skin cancers.¹²

The development of SCC is directly associated with cumulative lifetime sun exposure, and this is supported by the observation that the incidence of SCC increases with age with a predilection to develop on areas regularly exposed to the sun.¹³ UV radiation of the skin can cause mutations of p⁵³, a tumor suppressor gene, which can be found in roughly 90% of SCC.¹⁴ These mutations promote carcinogenesis by rendering cells resistant to apoptosis, allowing for the clonal expansion of precancerous keratinocytes.

The relationship between the timing of exposure to UV radiation and BCC is less clear. Studies suggest that BCC has a strong association with intermittent, recreational sun expo-