The Role of Inflammation in Skin Cancer

To estimate the incidence of nonmelanoma skin cancer (NMSC) in the US population in 2006 and secondarily to indicate trends in numbers of procedures for skin cancer treatment. A descriptive analysis of population-based claims and US Census Bureau data combined with a population-based cross-sectional survey using multiple US government data sets, including the Centers for Medicare and Medicaid Services Fee-for-Service Physicians Claims databases, to calculate totals of skin cancer procedures performed for Medicare beneficiaries in 1992 and from 1996 to 2006 and related parameters. The National Ambulatory Medical Care Service database was used to estimate NMSC-related office visits. We combined these to estimate totals of new skin cancer diagnoses and affected individuals in the overall US population. The total number of procedures for skin cancer in the Medicare fee-for-service population increased by 76.9% from 1 158 298 in 1992 to 2 048 517 in 2006. The age-adjusted procedure rate per year per 100 000 beneficiaries increased from 3514 in 1992 to 6075 in 2006. From 2002 to 2006 (the years for which the databases allow procedure linkage to patient demographics and diagnoses), the number of procedures for NMSC in the Medicare population increased by 16.0%. In this period, the number of procedures per affected patient increased by 1.5%, and the number of persons with at least 1 procedure increased by 14.3%. We estimate the total number of NMSCs in the US population in 2006 at 3 507 693 and the total number of persons in the United States treated for NMSC at 2 152 500. The number of skin cancers in Medicare beneficiaries increased dramatically over the years 1992 to 2006, due mainly to an increase in the number of affected individuals. Using nationally representative databases, we provide evidence of much higher overall totals of skin cancer diagnoses and patients in the US population than previous estimates. These data give the most complete evaluation to date of the underrecognized epidemic of skin cancer in the United States.

The matrix metalloproteinase MMP-9/gelatinase B is upregulated in angiogenic dysplasias and invasive cancers of the epidermis in a mouse model of multi-stage tumorigenesis elicited by HPV16 oncogenes. Transgenic mice lacking MMP-9 show reduced keratinocyte hyperproliferation at all neoplastic stages and a decreased incidence of invasive tumors. Yet those carcinomas that do arise in the absence of MMP-9 exhibit a greater loss of keratinocyte differentiation, indicative of a more aggressive and higher grade tumor. Notably, MMP-9 is predominantly expressed in neutrophils, macrophages, and mast cells, rather than in oncogene-positive neoplastic cells. Chimeric mice expressing MMP-9 only in cells of hematopoietic origin, produced by bone marrow transplantation, reconstitute the MMP-9-dependent contributions to squamous carcinogenesis. Thus, inflammatory cells can be coconspirators in carcinogenesis.

All organisms, from simple invertebrates to complex human beings, exist in different colors and patterns, which arise from the unique distribution of pigments throughout the body. Pigmentation is highly heritable, being regulated by genetic, environmental, and endocrine factors that modulate the amount, type, and distribution of melanins in the skin, hair, and eyes. In addition to its roles in camouflage, heat regulation, and cosmetic variation, melanin protects against UV radiation and thus is an important defense system in human skin against harmful factors. Being the largest organ of the body that is always under the influence of internal and external factors, the skin often reacts to those agents by modifying the constitutive pigmentation pattern. The focus of this review is to provide an updated overview of important physiological and biological factors that increase pigmentation and the mechanisms by which they do so. We consider endocrine factors that induce temporary (e.g., during pregnancy) or permanent (e.g., during aging) changes in skin color, environmental factors (e.g., UV), certain drugs, and chemical compounds, etc. Understanding the mechanisms by which different factors and compounds induce melanogenesis is of great interest pharmaceutically (as therapy for pigmentary diseases) and cosmeceutically (e.g., to design tanning products with potential to reduce skin cancer risk).