Predictors of tanning dependence in white non-Hispanic females and males.

BACKGROUND: Growing evidence suggests that some individuals may exhibit symptoms of dependence on ultraviolet (UV) light, a known carcinogen, in the context of tanning; however, few studies have investigated predictors of tanning dependence (TD). OBJECTIVE: To identify predictors of TD. METHODS: Non-Hispanics of European ancestry who had previously participated in a case-control study of early-onset basal cell carcinoma completed an online survey to ascertain TD and other behaviours (alcohol dependence, nicotine dependence, seasonal affective disorder (SAD), exercise 'addiction' and depression). Information on host factors, such as skin and eye colour and history of sunbathing and indoor tanning, was obtained from a study in which the participants were previously enrolled. Lifetime TD was assessed using the modified Cut down, Annoyed, Guilty, Eye-opener (mCAGE) and the modified Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (mDSM-IV-TR) questionnaires. Participants were classified as 'TD' if positive on both questionnaires and not TD if negative on both questionnaires. RESULTS: In total, 499 individuals completed the online survey (81.9% participation rate), and 24.4% were classified as 'TD'. In the multivariate model, women were more likely to be TD [odds ratio (OR) 6.93; 95% confidence intervals (95% CI) (3.36-14.27)] than men. Alcohol dependence (OR 6.55: 95% CI 3.19-13.42), SAD (OR 2.77; 95% CI 1.26-6.09) and exercise 'addiction' (OR 5.47; 95% CI 1.15-26.06) were all significant predictors for TD. CONCLUSION: Increased knowledge of those at risk for TD will allow appropriate interventions to be designed.

Alcohol intake and early-onset basal cell carcinoma in a case-control study.

BACKGROUND: Previous epidemiological studies of overall alcohol intake and basal cell carcinoma (BCC) are inconsistent, with some evidence for differences by type of alcoholic beverage. While alcohol may enhance the carcinogenicity of ultraviolet (UV) radiation, this has not been evaluated in existing epidemiological studies. OBJECTIVES: To evaluate alcohol intake in relation to early-onset BCC, and explore potential interactions with UV exposure. METHODS: Basal cell carcinoma cases (n = 380) and controls with benign skin conditions (n = 390) under 40 years of age were identified through Yale Dermatopathology. Participants provided information on lifetime alcohol intake, including type of beverage, during an in-person interview. Self-reported data on indoor tanning and outdoor sunbathing were used to categorize UV exposure. We calculated odds ratios (OR) and 95% confidence intervals (CIs) using unconditional multivariate logistic regression in the full sample and in women only. RESULTS: There was no statistically significant association between lifetime alcohol intake and early-onset BCC overall [above median intake vs. no regular alcohol intake (OR 1·10, 95% CI 0·69-1·73)] or in women only (OR 1·21, 95% CI 0·73-2·01). Similarly, intake of red wine, white wine, beer or spirits and mixed drinks was not associated with early-onset BCC. In exploratory analyses, we saw limited evidence for an interaction (P(interaction) = 0·003), with highest risk for high alcohol and high UV exposures, especially in women, but subgroup risk estimates had wide and overlapping CIs. CONCLUSIONS: Overall, we did not observe any clear association between lifetime alcohol intake and early-onset BCC.

The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas.

Basal cell carcinoma (BCC) is the most common cancer in humans. The majority of sporadic BCCs have allele loss on chromosome 9q22 implying that inactivation of a tumour suppressor in this region is an important step in BCC formation. The gene for nevoid basal cell carcinoma syndrome (NBCCS), an autosomal dominant disorder characterized by multiple BCCs, maps to the same region and is presumed to be the tumour suppressor inactivated at this site. NBCCS has been identified recently and encodes a protein with strong homology to the Drosophila segment polarity gene, patched. Analysis of Drosophila mutants indicates that patched interacts with the hedgehog signalling pathway, repressing the expression of various hedgehog target genes including wingless, decapentaplegic and patched itself. Using single strand conformational polymorphism (SSCP) to screen human patched in 37 sporadic BCCs, we detected mutations in one-third of the tumours. Direct sequencing of two BCCs without SSCP variants revealed mutations in those tumours as well suggesting that inactivation of patched is probably a necessary step in BCC development. Northern blots and RNA in situ hybridization showed that patched is expressed at high levels in tumour cells but not normal skin suggesting that mutational inactivation of the gene leads to overexpression of mutant transcript owing to failure of a negative feedback mechanism.

Relationship between sunlight exposure and a key genetic alteration in basal cell carcinoma.

BACKGROUND: Basal cell carcinoma (BCC) of the skin is the most common cancer in humans. Epidemiologic studies implicate sunlight exposure as one risk factor, but the limited association between BCCs and UVB radiation (i.e., UV radiation of a wavelength of 280-320 nm) suggests that additional factors must be involved. At the molecular level, not much is known about the role of specific environmental agents in the pathogenesis of BCCs. Point mutations of the types produced by UVB radiation are seen in the p53 gene (also known as TP53; chromosome 17p) of 40%-56% of BCCs. Loss of heterozygosity (LOH) on chromosome 9q22, however, is the most frequent genetic alteration in these tumors, and its causative agent is unknown. PURPOSE: We investigated whether the genetic alteration in chromosome 9 is common to all clinical subtypes of BCCs and whether inactivation of this putative tumor suppressor is related to sunlight exposure. The presence of UVB radiation-related point mutations in the p53 gene was used as an internal control for sunlight exposure to the precursor cells. METHODS: Tumor and blood samples were obtained from skin cancer patients by a surgeon who used Mohs' micrographic surgical technique. Clinical information on each tumor included location, size, histologic, subtype and whether it was primary or recurrent and sporadic or hereditary. Sixty BCCs from 58 patients were evaluated for LOH with 12 polymorphic markers that span chromosome 9. A subset of 18 tumors was evaluated for point mutations in exons 2-11 of the p53 gene, and a subset of 26 tumors was evaluated for LOH by use of a polymorphism in exon 4 of the p53 gene. Associations between tumor characteristics and molecular alterations were tested by a two-tailed chi-squared analysis or a two-tailed Fisher's exact test, depending on sample size. RESULTS: In a clinically diverse series of 47 informative tumors, 32 (68%) showed LOH for chromosome 9q markers, irrespective of histologic characteristics or clinical behavior. Forty-four (94%) of the 47 tumors were from sun-exposed areas of the body, defined as the head and neck in both sexes, shoulders or chest in males, and legs in females. No association was found between chromosome 9q LOH and sunlight exposure, as assessed by either the location of tumors on the body or the presence of UVB radiation-related p53 mutations. Of note, there was a striking difference between the frequency of LOH on chromosome 17p (two [12.5%] of 16 informative tumors) and on chromosome 9q (32 [68%] of 47 informative tumors; P < .001). CONCLUSIONS: Inactivation of a gene on chromosome 9q22 may be a necessary event for basal cell carcinogenesis. The pathogenesis of mutations in this gene may involve factors other than sunlight in a large proportion of tumors. IMPLICATIONS: The limited association between sunlight exposure and BCC incidence may reflect an etiologic contribution of additional environmental agents.

Nevoid basal cell carcinoma syndrome.

The nevoid basal cell carcinoma syndrome is an autosomal dominant disorder that predisposes to basal cell carcinomas of the skin, ovarian fibromas, and medulloblastomas. Unlike other hereditary disorders associated with cancer, it features widespread developmental defects. Laboratory studies of radiation sensitivity and chromosome instability over the past 20 years have generally yielded negative or inconclusive results. Recently, screening for allelic loss in sporadic and hereditary basal cell carcinomas, hereditary ovarian fibromas, and sporadic medulloblastomas provided evidence for a tumor suppressor gene on chromosome 9q, important in all three tumor types. Demonstration of a chromosome 9q deletion in an unusual patient with this syndrome and genetic linkage studies in large kindreds indicated that the nevoid basal cell carcinoma syndrome gene maps to the exact same location lost in tumors. These data show that tumors arise with homozygous inactivation of the gene and imply that it normally functions as a tumor suppressor. In contrast, hemizygous germ-line mutations lead to multiple congenital anomalies.

The molecular basis of nonmelanoma skin cancer: new understanding.

Nonmelanoma skin cancers, including basal cell carcinomas and squamous cell carcinomas, represent the most common malignant neoplasms in humans. Although many environmental and genetic factors contribute to the development of skin cancers, the most important is chronic exposure to UV radiation in sunlight. We now appreciate that the role of UV in the development of nonmelanoma skin cancers is 2-fold. First, UV radiation causes mutations in cellular DNA. Failure to repair these genetic alterations ultimately leads to unrestrained growth and tumor formation. Second, UV radiation has profound effects on the cutaneous immune system, inducing a state of relative immunosuppression that prevents tumor rejection. The purpose of this review is to educate clinical dermatologists about the recent developments in molecular biology and immunology that have greatly enhanced our understanding of how skin cancers arise. The clinical implications of this new knowledge are far-reaching and likely to soon impact the diagnosis, treatment, and prevention of a variety of benign and malignant skin conditions. It will be important for the clinician to understand the biological mechanisms underlying these new therapeutic developments to implement them effectively.

In vivo fluorescence of human skin. A potential marker of photoaging.

Fluorescence is a feature of elastin and collagen, both major compounds of human dermis that are altered by age and photoexposure. We studied the intrinsic fluorescence of skin in vivo in 28 human volunteers to determine whether photoaging and chronologic aging of the skin could be evaluated by this noninvasive technique. We demonstrate that the excitation of skin autofluorescence by laser ultraviolet radiation yields characteristic tissue fluorescence spectra that are unrelated to age, pigmentation, or skin thickness. The differences in skin autofluorescence appear to be related to photoexposure. Thus, laser-induced fluorimetry, a noninvasive technique, may be adaptable as a marker of photoaging.

Aggressive-growth basal cell carcinoma in young adults.

Aggressive-growth basal cell carcinoma (AG-BCC) defines a group of basal cell cancers that are histologically and clinically aggressive. This group includes morpheaform, infiltrating, and recurrent BCCs. Because of the clinical observation that the incidence of AG-BCC may be increased in patients under 35 years of age, compared with those older, we performed a retrospective study. We reviewed the pathologic findings of 3381 patients diagnosed with BCC, including 102 patients with BCC referred for Mohs surgery to determine whether AG-BCC occurs with increased frequency in patients younger than than 35 years of age. Among patients under 35 years of age, 38% of women had AG-BCC compared with 9% of women in the older age group. Similarly, 25% of men under 35 years of age had AG-BCC compared with 11% among men in the older age group. Aggressive-growth BCC is more frequently noted in patients under 35 years of age than in those older. Failure to diagnose this type of BCC, which may be clinically subtle, may lead to incomplete or inadequate treatment. Because of the tendency of these tumors to recur, greater long-term morbidity may result.

Electrosurgical facial resurfacing: a prospective multicenter study of efficacy and safety.

BACKGROUND: A novel electrosurgical technology that uses a bipolar electrode-tipped stylet to deliver relatively low-radiofrequency energy through an electrically conductive medium has been developed. OBJECTIVE: To evaluate the efficacy and safety of the radiofrequency resurfacing system for the treatment of facial wrinkles. DESIGN: Multicenter, prospective, noncomparative study with longitudinal follow-up. SETTING: Four US academic dermatologic surgery clinics. PATIENTS: Ninety-five patients with mild to severe photodamage (Fitzpatrick classes I-III) involving periorbital (75 treatment sites) and perioral (50 sites) facial skin. INTERVENTION: Radiofrequency resurfacing with the use of 2 to 3 passes at 125 or 139 V. MAIN OUTCOME MEASURES: Wrinkle and cosmetic improvements evaluated by patients, investigators, and, by means of photographs, an independent panel of 5 evaluators. RESULTS: All evaluators determined a positive mean improvement in wrinkles for both periorbital and perioral anatomic sites, with greater improvement for patients with more severe wrinkles at baseline. An increased number of passes and higher voltage settings had a positive impact on wrinkle improvement. Transient postinflammatory hyperpigmentation occurred in 26% of periorbital and 4% of perioral sites. Hypertrophic scars occurred in 3.8% of treatment sites, with all but 1 scar resolving by 6 months. For the most part, healing was rapid, pain was minimal, and erythema largely resolved within 2 months. Other untoward effects were relatively few and short-lived. CONCLUSIONS: At the study settings used, radiofrequency resurfacing is an effective modality in the treatment of periorbital and perioral wrinkles in patients with Fitzpatrick class I, II, and III photodamage. There is less severe postoperative morbidity than seen with carbon dioxide or coagulating erbium:YAG lasers. The potential risks are similar to those seen with other resurfacing modalities.

Lasers in dermatology and ophthalmology.

Dermatology and ophthalmology are two specialties that have made exceptional use of laser technology. In dermatology, port wine stains and hemangiomas, neoplastic lesions, and adnexal tumors are amenable to laser treatment. In ophthalmology, the use of lasers to effect photocoagulation, photoradiation, photovaporization, photodisruption, and photodecomposition has permitted the treatment of vascular retinal disease, macular edema, intraocular tumors, open angle glaucoma, and angle closure glaucoma. Although great strides in laser technology have been made, the future is even more promising as laser devices are further modified to treat specific disease processes.

Preoperative assessment of the elderly patient.

Preoperative assessment of the elderly patient for surgery is vital to the success of the surgical procedure. A thorough evaluation must first begin with an understanding of the physiologic and pathophysiologic changes unique to the elderly patient and the aging skin. A complete preoperative assessment entails assessing the patient and dermatologic problem, preparing the patient and caregivers for the surgery and its expected outcomes, and highlighting issues and problems that need to be managed prior to the procedure. With the continued growth of the geriatric population, all dermatologic surgeons should be aware of the special issues related to their geriatric patients. With heightened awareness of and screening for potential pitfalls in the elderly surgical patient, adverse outcomes can be avoided.

Nonexcisional treatment of benign and premalignant cutaneous lesions.

The correct diagnosis of benign and premalignant cutaneous lesions requires appropriate biopsy techniques that reflect an understanding of the specific cutaneous pathology. Violation of the basement membrane zone generally results in scarring. Knowledge of the healing processes of the epidermis, dermis, and subcutis permit the least destructive diagnostic and treatment techniques, resulting in the best functional and cosmetic results. Excessive scarring or procedures inappropriate to the lesion under consideration should be avoided.

Water-in-oil emollients as steroid-sparing adjunctive therapy in the treatment of psoriasis.

An open label study of ninety-six patients with chronic plaque-type psoriasis demonstrated the efficacy of the addition of water-in-oil emollients to a topical corticosteroid regimen. Twice daily application of betamethasone dipropionate cream and once daily application of both betamethasone dipropionate cream and either a water-in-oil based moisturizing cream or lotion were equivalent in efficacy (p = 0.05). Once daily application of both betamethasone dipropionate cream and either a water-in-oil based cream or lotion was significantly better than once daily application of betamethasone dipropionate cream alone (p = 0.05). Water-in-oil emollients are useful in the therapy of chronic, plaque-type psoriasis and provide a steroid-sparing effect.

PTCH codon 1315 polymorphism and risk for nonmelanoma skin cancer.

BACKGROUND: The PTCH tumour suppressor gene is involved in the development of nearly all basal cell carcinomas (BCCs) of the skin and a fraction of squamous cell carcinomas (SCCs). A nonconservative Pro/Leu nucleotide polymorphism within PTCH exon 23 at codon 1315 was recently reported to be potentially important for the development of breast epithelial cell cancers. Objectives Accordingly, the status of PTCH codon 1315 was analysed for a possible association with the development of nonmelanoma skin cancers (NMSCs) in a pilot study. Because skin cancer risk is affected by specific population-dependent phenotypes such as skin and hair colour, codon 1315 was also analysed for normal allele frequency variation in human populations having differing extents of eumelanin vs. phaeomelanin. METHODS: The single nucleotide polymorphism in codon 1315 of the human PTCH gene was analysed in genomic DNA from six different populations comprising 472 blood samples and from 170 patients in four different categories with NMSC. Polymerase chain reaction and pyrosequencing were used to determine the allele frequencies. Allelic loss was furthermore determined in tumours following microdissection. RESULTS: The Pro/Pro genotype frequency ranged from 30% to 65% between populations, with a significant trend for a reduced frequency of the Pro/Pro genotype in populations having lighter pigmentation (P = 0.020). Pro/Pro frequency showed an increasing trend with increasing tumour case severity (P = 0.027). In 260 samples from 180 Swedish patients with NMSC and a control group of 96 healthy ethnically matched volunteers, no statistically significant pairwise differences between groups were detected in the PTCH codon 1315 allelic distribution, neither was a difference seen for multiple or early onset cases of BCC in the Swedish population. In Swedish patients with single tumours, allelic loss (loss of heterozygosity) was observed in 20 of 30 (67%) patients with BCC and four of 22 (18%) patients with SCC, with no preference in the allele lost. In contrast, the Pro/Pro genotype was frequent in seven U.S. patients having multiple independent BCCs. One of these patients was heterozygous, enabling allelic loss studies. Of 20 independent tumours, 11 had lost an allele; 10 of the 11 had lost Leu, suggesting nonrandom loss that favoured retention of Pro (P = 0.0059). CONCLUSIONS: Our results indicate an association between the eumelanin-to-phaeomelanin shift and a shift from the Pro/Pro genotype to Leu-containing genotypes. Failure to lose Pro during the shift to phaeomelanin may be associated with an increased population risk for BCC and increased individual risk for multiple BCC. During development of a tumour, the effect of Pro may be magnified by loss of the Leu allele.

An educational device for Mohs micrographic surgery. A three-dimensional model of basal cell carcinoma.

Mohs micrographic surgery for skin cancer (fresh-tissue technique) involves the processing of tissue in a complex fashion. The advantages of this method relate to the asymmetric three-dimensional growth of basal cell carcinoma (BCC). A device is described here based on published knowledge about the growth of BCC. The model demonstrates the precise way in which Mohs surgery varies from other surgical approaches to yield higher cure rates in specific circumstances. This device may be helpful in educating residents and medical students about Mohs surgery and in preparing patients for this procedure.