A meta-analysis of pigmentary characteristics, sun sensitivity, freckling and melanocytic nevi and risk of basal cell carcinoma of the skin

Objective: To calculate pooled risk estimates of the association between pigmentary characteristics and basal cell carcinoma (BCC) of the skin. Methods: We searched three electronic databases and reviewed the reference lists of the retrieved articles until July 2012 to identify eligible epidemiologic studies. Eligible studies were those published in between 1965 and July 2012 that permitted quantitative assessment of the association between histologically-confirmed BCC and any of the following characteristics: hair colour, eye colour, skin colour, skin phototype, tanning and burning ability, and presence of freckling or melanocytic nevi. We included 29 studies from 2236 initially identified. We calculated summary odds ratios (ORs) using weighted averages of the log OR, using random effects models. Results: We found strongest associations with red hair (OR 2.02; 95% CI: 1.68, 2.44), fair skin colour (OR 2.11; 95% CI: 1.56, 2.86), and having skin that burns and never tans (OR 2.03; 95% CI: 1.73, 2.38). All other factors had weaker but positive associations with BCC, with the exception of freckling of the face in adulthood which showed no association. Conclusions: Although most studies report risk estimates that are in the same direction, there is significant heterogeneity in the size of the estimates. The associations were quite modest and remarkably similar, with ORs between about 1.5 and 2.5 for the highest risk level for each factor. Given the public health impact of BCC, this meta-analysis will make a valuable contribution to our understanding of BCC.

Cytogenetics of primary skin tumors

Skin tumors can arise as a result of cumulative genetic abnormalities, including chromosomal ­aberrations that can be described as either morphological (structural rearrangements) or molecular (copy number variations). Cytogenetic techniques have been used to examine both large and small chromosomal aberrations, and include karyotyping, comparative genomic hybridization, and fluorescence in situ hybridization. This chapter describes the recurrent aberrations associated with skin tumors, such as benign melanocytic nevi, melanoma, basal cell carcinoma, squamous cell carcinoma, actinic (solar) keratosis, Bowen’s disease, keratoacanthoma, Merkel cell carcinoma, dermatofibrosarcoma protuberans, and cutaneous lymphomas, as detected by cytogenetic methodologies. A significant number of genomic aberrations are shared across different subtypes of skin tumors, including structural and numerical alterations of chromosome 1, −3p, +3q, +6, +7, +8q, −9p, +9q, −10, −17p, +17q and +20. Aberrations specific to certain skin cancers have also been detected, and include: loss of 18q in squamous cell carcinoma, but not its precursor, actinic keratosis; loss of 9q22 in sporadic basal cell carcinoma; and translocation involving 17q22 and 22q13 in dermatofibrosarcoma protuberans. These regions contain a number of potential candidate genes that are involved in aspects of cell signaling, proliferation, differentiation, and apoptosis. Cytogenetic methodologies continue to evolve with the advent of array-based comparative genomic hybridization, copy number variation microarrays, and next-generation sequencing. It is envisioned that cytogenetic analysis will continue to be employed for identification and further exploration of novel chromosomal regions and associated genes that drive skin tumorigenesis.

Cytogenetics of melanoma and nonmelanoma skin cancer

Cytogenetic analysis of melanoma and nonmelanoma skin cancers has revealed recurrent aberrations, the frequency of which is reflective of malignant potential. Highly aberrant karyotypes are seen in melanoma, squamous cell carcinoma, solar keratosis and Merkel cell carcinoma with more stable karyotypes seen in basal cell carcinoma, keratoacanthoma, Bowen’s disease, dermatofibrosarcomarotuberans and cutaneous lymphomas. Some aberrations were common amongst a number of skin cancer types including rearrangements and numerical abnormalities of chromosome 1, −3p, +3q, partial or entire trisomy 6, trisomy 7, +8q, −9p, +9q, partial or entire loss of chromosome 10, −17p, + 17q and partial or entire gain of chromosome 20. Combination of cytogenetic analysis with other molecular genetic techniques has enabled the identification of not only aberrant chromosomal regions, but also the genes that contribute to a malignant phenotype. This review provides a comprehensive summary of the pertinent cytogenetic aberrations associated with a variety of melanoma and nonmelanoma skin cancers.

Polymorphisms of the VDR gene are associated with presence of solar keratoses on the skin

Background Vitamin D has a range of biological effects including antiproliferative functions that are mediated through its receptors, encoded by the VDR gene. Objectives We investigated polymorphisms within the VDR gene for association with solar keratosis (SK), a biomarker for skin cancer, and examined interactions with skin phenotype. Methods Among participants of the community-based Nambour Skin Cancer Study, we genotyped 190 people with SKs and 190 without for ApaI, TaqI and FokI polymorphisms. Results We found a significant difference in genotype frequencies of the TaqI polymorphism between affected and unaffected populations (P = 0Æ008). The TT ⁄tt genotype group was associated with a twofold increase in odds of being affected by one or more SK. Individuals with fair skin and the TT ⁄tt genotype had about a sevenfold increase, whereas fair-skinned people with the Tt genotype had a fourfold increase in odds of being affected by SK. Individuals with the TT ⁄tt genotype who were prone to burn and not tan on acute sun exposure had about a sixfold increase in odds of SK. Fair-skinned people with VDR-Apa AA ⁄aa genotypes had about an eightfold increase in odds of being affected by SK compared with a fivefold increase in individuals with the Aa genotype and fair skin. Conclusions The trend for homozygote genotypes to increase the odds of SK suggests that intermediate VDR activity is important in protection or that the heterodimer formed by a heterozygous genotype may have an altered binding potential. Overall, these analyses indicate that VDR may be important in SK development.

Cytogenetic alterations in nonmelanoma skin cancer : a review

Since the advent of cytogenetic analysis, knowledge about fundamental aspects of cancer biology has increased, allowing the processes of cancer development and progression to be more fully understood and appreciated. Classical cytogenetic analysis of solid tumors had been considered difficult, but new advances in culturing techniques and the addition of new cytogenetic technologies have enabled a more comprehensive analysis of chromosomal aberrations associated with solid tumors. Our purpose in this review is to discuss the cytogenetic findings on a number of nonmelanoma skin cancers, including squamous- and basal cell carcinomas, keratoacanthoma, squamous cell carcinoma in situ (Bowen's disease), and solar keratosis. Through classical cytogenetic techniques, as well as fluorescence-based techniques such as fluorescence in situ hybridization and comparative genomic hybridization, numerous chromosomal alterations have been identified. These aberrations may aid in further defining the stages and classifications of nonmelanoma skin cancer and also may implicate chromosomal regions involved in progression and metastatic potential. This information, along with the development of newer technologies (including laser capture microdissection and comparative genomic hybridization arrays) that allow for more refined analysis, will continue to increase our knowledge about the role of chromosomal events at all stages of cancer development and progression and, more specifically, about how they are associated with nonmelanoma skin cancer.

Focussing on genomic and phenomic correlations in respiration of non-melanotic skin cancers

In recent years, with the development of techniques in modern molecular biology, it has become possible to study the genetic basis of carcinogenesis down to the level of DNA sequence. Major advances have been made in our understanding of the genes involved in cell cycle control and descriptions of mutations in those genes. These developments have led to the definition of the role of specific oncogenes and tumour suppressor genes in several cancers, including, for example, colon cancers and some forms of breast cancer. Work reported from our laboratory has led to the identification of a number of candidate genes involved in the development of non-melanotic skin cancers. In this chapter, we attempt to further explain the observed (phenomic) alterations in metabolic pathways associated with oxygen consumption with the changes at the genetic level.

Cytogenetics of basal cell carcinoma and squamous cell carcinomas

Cytogenetic analysis is a powerful tool that allows analysis of chromosomal aberrations associated with diseased states. In particular, a combination of cytogenetic techniques has allowed the identification of aberrations associated with cancer development, including cancers of the skin. This chapter provides a comprehensive overview of cytogenetic alterations in basal and squamous cell carcinomas of the skin. These two distinct lesions have altered karyotypes that are consistent with their malignant potential. Basal cell carcinomas, although relatively stable lesions, are highly associated with recurrent aberrations of chromosomes 6, 7, 9 and X, as detected by a number of cytogenetic techniques. Squamous cell carcinomas, on the other hand are associated with a much higher degree of instability, involving aberrations of chromosomes 3, 7, 8, 11, 13, 17 and 18, as detected using a number of cytogenetic techniques. Overall, the numbers and types of aberrations associated with basal and squamous cell carcinoma, define the characteristic behaviour associated with these lesions and identification of these aberrations may aid in the understanding of malignant potential, prognosis and treatment of these skin cancers.

Current status of pharmacogenomics testing for anti-tumor drug therapies : approaches to non-melanoma skin cancer

Skin cancer is one of the most commonly occurring cancer types, with substantial social, physical, and financial burdens on both individuals and societies. Although the role of UV light in initiating skin cancer development has been well characterized, genetic studies continue to show that predisposing factors can influence an individual's susceptibility to skin cancer and response to treatment. In the future, it is hoped that genetic profiles, comprising a number of genetic markers collectively involved in skin cancer susceptibility and response to treatment or prognosis, will aid in more accurately informing practitioners' choices of treatment. Individualized treatment based on these profiles has the potential to increase the efficacy of treatments, saving both time and money for the patient by avoiding the need for extensive or repeated treatment. Increased treatment responses may in turn prevent recurrence of skin cancers, reducing the burden of this disease on society. Currently existing pharmacogenomic tests, such as those that assess variation in the metabolism of the anticancer drug fluorouracil, have the potential to reduce the toxic effects of anti-tumor drugs used in the treatment of non-melanoma skin cancer (NMSC) by determining individualized appropriate dosage. If the savings generated by reducing adverse events negate the costs of developing these tests, pharmacogenomic testing may increasingly inform personalized NMSC treatment.

The incidence and predictors of lower limb split skin graft failure and primary closure dehiscence in day case surgical patients

This project was an observational study of outpatients following lower limb surgical procedures for removal of skin cancers. Findings highlight a previously unreported high surgical site failure rate. Results also identified four potential risk factors (increasing age, presence of leg pain, split skin graft and haematoma) which negatively impact on surgical site healing in this population.

Skin cancer prevention and fashion – frontier bedfellows

Problem Queensland has the highest rates of skin cancer in the world, even after wide-ranging public programs promoting sun safety awareness. To-date, public awareness campaigns on the dangers of excessive sun exposure have been highly successful. For adolescents, however, where a significant amount of lifetime sun exposure occurs, perilous exposure still ensues, despite awareness of the risks. New frontier approaches are required to target this key audience cluster, for this significant national problem. Approach For the majority of adolescents, being part of a collective norm defines their visual, attitudinal and behavioural actions and fashion has been validated as one of the most powerful forces that can form, shape and bolster these norms. Considering clothing is the easiest method to limit the amount of skin exposed to UV, fashion (in its many subtle, yet influential guises) is proposed as an avenue to advance positive sun safe practices for adolescents. Through an action-led methodology, this research explores the potential of fashion, as one of the key parts of a complex equation, to be a prime driver to facilitate sun safety for adolescents. Findings This paper advocates that fashion, as distinguishable from clothing, has the potential to positively influence sun protective behaviour. The findings go further and recommend the use of fashion as a stealth driver for sun safety advancement, for adolescents in particular, via shifts in norms of beauty and targeted generational communication strategies. This frontier approach has the potential to significantly reduce risky sun exposure in adolescence.

Skin cancer detection by one click - are we any closer?

To the editor...

Characterisation of a human skin equivalent model to study the effects of ultraviolet B radiation on keratinocytes

The incidences of skin cancers resulting from chronic ultraviolet radiation (UVR) exposure are on the incline both in Australia and globally. Hence, the cellular and molecular pathways associated with UVR-induced photocarcinogenesis urgently need to be elucidated, in order to develop more robust preventative and treatment strategies against skin cancers. In vitro investigations into the effects of UVR (in particular the highly-mutagenic UVB wavelength) have, to date, mainly involved the use of cell culture and animal models. However, these models possess biological disparities to native skin, which to some extent have limited their relevance to the in vivo situation. To address this, we characterised a 3-dimensional, tissue-engineered human skin equivalent (HSE) model (consisting of primary human keratinocytes cultured on a dermal-derived scaffold) as a representation of a more physiologically-relevant platform to study keratinocyte responses to UVB. Significantly, we demonstrate that this model retains several important epidermal properties of native skin. Moreover, UVB-irradiation of the HSE constructs was shown to induce key markers of photodamage in the HSE keratinocytes, including the formation of cyclobutane pyrimidine dimers, the activation of apoptotic pathways, the accumulation of p53 and the secretion of inflammatory cytokines. Importantly, we also demonstrate that the UVB-exposed HSE constructs retain the capacity for epidermal repair and regeneration following photodamage. Together, our results demonstrate the potential of this skin equivalent model as a tool to study various aspects of the acute responses of human keratinocytes to UVB radiation damage.

Interventions to decrease skin cancer risk in outdoor workers : update to a 2007 systematic review

BACKGROUND: Outdoor workers are at high risk of harmful ultraviolet radiation exposure and are identified as an at risk group for the development of skin cancer. This systematic evidence based review provides an update to a previous review published in 2007 about interventions for the prevention of skin cancer in outdoor workers. RESULTS: This review includes interventions published between 2007-2012 and presents findings about sun protection behaviours and/or objective measures of skin cancer risk. Six papers met inclusion criteria and were included in the review. Large studies with extended follow-up times demonstrated the efficacy of educational and multi-component interventions to increase sun protection, with some higher use of personal protective equipment such as sunscreen. However, there is less evidence for the effectiveness of policy or specific intervention components. CONCLUSIONS: Further research aimed at improving overall attitudes towards sun protection in outdoor workers is needed to provide an overarching framework.