The most important cause of<unk>  formation is solar radiation, through a variety of mechanisms. Mutation of the p53 tumor suppressor gene, induced by UV radiation, has been identified as a crucial step in<unk>  formation. This tumor suppressor gene, located on chromosome 17p132, allows for cell cycle arrest when DNA or RNA is damaged. Dysregulation of the p53 pathway can thus result in unchecked replication of dysplastic keratinocytes, thereby serving as a source of neoplastic growth and the development of<unk> , as well as possible progression from<unk>  to skin cancer. Other molecular markers that have been associated with the development of<unk>  include the expression of p16ink4, p14, the CD95 ligand, TNF-related apoptosis-inducing ligand (TRAIL) and TRAIL receptors, and loss of heterozygosity. Evidence also suggests that the human papillomavirus (HPV) plays a role in the development of<unk> s. The HPV virus has been detected in<unk> s, with measurable HPV viral loads (one HPV-DNA copy per less than 50 cells) measured in 40% of<unk> s. Similar to UV radiation, higher levels of HPV found in<unk> s reflect enhanced viral DNA replication. This is suspected to be related to the abnormal keratinocyte proliferation and differentiation in<unk> s, which facilitate an environment for HPV replication. This in turn may further stimulate the abnormal proliferation that contributes to the development of<unk> s and carcinogenesis. Ultraviolet radiation It is thought that ultraviolet (UV) radiation induces mutations in the keratinocytes of the epidermis, promoting the survival and proliferation of these atypical cells. Both UV-A and UV-B radiation have been implicated as causes of<unk> s. UV-A radiation (wavelength 320–400 nm) reaches more deeply into the skin and can lead to the generation of reactive oxygen species, which in turn can damage cell membranes, signaling proteins, and nucleic acids. UV-B radiation (wavelength 290–320 nm) causes thymidine dimer formation in DNA and RNA, leading to significant cellular mutations. In particular, mutations in the p53 tumor suppressor gene have been found in 30–50% of<unk>  lesion skin samples. UV radiation has also been shown to cause elevated inflammatory markers such as arachidonic acid, as well as other molecules associated with inflammation. Eventually, over time these changes lead to the formation of<unk> s. Several predictors for increased<unk>  risk from UV radiation have been identified: * Extent of sun exposure: Cumulative sun exposure leads to an increased risk for development of<unk> s. In one U.S. study,<unk> s were found in 55% of fair-skinned men with high cumulative sun exposure, and in only 19% of fair-skinned men with low cumulative sun exposure in an age-matched cohort (the percents for women in this same study were 37% and 12% respectively). Furthermore, the use of sunscreen (SPF 17 or higher) has been found to significantly reduce the development of<unk>  lesions, and also promotes the regression of existing lesions. * History of sunburn: Studies show that even a single episode of painful sunburn as a child can increase an individual's risk of developing<unk>  as an adult. Six or more painful sunburns over the course of a lifetime was found to be significantly associated with the likelihood of developing<unk> . Skin pigmentation<unk>  on the forehead of a male Melanin is a pigment in the epidermis that functions to protect keratinocytes from the damage caused by UV radiation; it is found in higher concentrations in the epidermis of darker-skinned individuals, affording them protection against the development of<unk> s. Fair-skinned individuals have a significantly increased risk of developing<unk> s when compared to olive-skinned individuals (odds ratios of 14.1 and 6.5, respectively), and<unk> s are uncommon in dark-skinned people of African descent. Other phenotypic features seen in fair-skinned individuals that are associated with an increased propensity to develop<unk> s include: *Freckling * Light hair and eye color * Propensity to sunburn * Inability to tan Other risk factors *Immunosuppression: People with a compromised immune system from medical conditions (such as AIDS) or immunosuppressive therapy (such as chronic immunosuppression after organ transplantation, or chemotherapy for cancer) are at increased risk for developing<unk> s. They may develop<unk>  at an earlier age or have an increased number of<unk>  lesions compared to immunocompetent people. * Human papillomavirus (HPV): The role of HPV in the development of<unk>  remains unclear, but evidence suggests that infection with the betapapillomavirus type of HPV may be associated with an increased likelihood of<unk> . *Genodermatoses: Certain genetic disorders interfere with DNA repair after sun exposure, thereby putting these individuals at higher risk for the development of<unk> s. Examples of such genetic disorders include xeroderma pigmentosum and Bloom syndrome. * Balding:<unk> s are commonly found on the scalps of balding men. The degree of baldness seems to be a risk factor for lesion development, as men with severe baldness were found to be seven times more likely to have 10 or more<unk> s when compared to men with minimal or no baldness. This observation can be explained by an absence of hair causing a larger proportion of scalp to be exposed to UV radiation if other sun protection measures are not taken.
Actinic keratosis
Squamous cell skin cancer
Hydrocarbon keratosis
Arsenical keratosis
Reactional keratosis
Seborrheic keratosis
Smokeless tobacco keratosis
PUVA keratosis