Early-onset Basal Cell Carcinoma Research Articles

18F-FDG PET/CT and Whole-Body Bone Scan Findings in Gorlin-Goltz Syndrome.

Gorlin-Goltz syndrome (basal cell nevus syndromes) is an uncommon, autosomal dominant inherited disorder characterized by developing basal cell carcinomas from a young age. Other distinct clinical features include keratocystic odontogenic tumors, dyskeratotic palmar and plantar pitting, and skeletal abnormalities. Clinicopathological findings of the syndrome are very diverse, and many symptoms manifest during a certain period of life. We present the compelling whole-body bone scan and 18F-FDG PET/CT findings in a 32-year-old man with odontogenic keratocyst, early-onset basal cell carcinoma, multiple ectopic calcifications in extremities, calcified falx cerebri, spinal scoliosis, macrocephaly, and ocular hypertelorism.

Basal Cell Carcinoma and Hedgehog Pathway Inhibitors: Focus on Immune Response.

Basal cell carcinoma (BCC) is the most common form of skin cancer, affecting more often elderly patients, but sometimes even younger ones, particularly if immunocompromised or genetically predisposed. Specifically, the Gorlin-Goltz syndrome, an autosomal dominant genodermatosis, also known as nevoid basal cell carcinoma syndrome, characterizes for multiple early onset BCCs. It is caused by a germline mutation in PTCH1, a tumor suppressor gene whose product is the key component of Hedgehog (Hh) signaling pathway, which also appears somatically mutated in more than 85% of sporadic BCCs. Hh pathway inhibitors vismodegib and sonidegib are currently indicated for BCC, in adults with advanced or recurred tumor following surgery or radiation therapy. The principal mechanism of action of these drugs is the inhibition of Smoothened (SMO), a transmembrane protein involved in Hh signal transduction, that plays a role in both cellular differentiation and cancer development. Some studies have reported effects of Hh pathway inhibitors at different levels of the immune response, from cytotoxic T cells to a modified local cytokines pattern. Given the specific relation between immune system and BCC development in some conditions, we will review BCC with focus on immune system changes mediated by Hh signaling pathway and induced by the inhibitors vismodegib and sonidegib in the treatment of BCC. Thus, we will give an overview of their effects on the local immune response, as well as a brief note on the supposed function of Hh pathway inhibition on the systemic one.

Risk factors for early-onset basal cell carcinomas and the trend towards their female predominance.

A dramatic rise in the incidence rates of basal cell carcinoma (BCC) in young women has been reported. We investigate potential risk factors (RF) for sporadic BCC in young patients and the current distribution of such RF in the general population of Catalonia, comparing the differences among men and women. A case-control study was performed, 69 BCCs diagnosed in patients ≤45 years of age vs. 69 healthycontrols. Afterward, 1,078 participants from the general population completed an RF questionnaire. Repeated sunburns were more frequent in instances of early-onset BCC in covered skin than in sun-exposed skin (P = 0.029). In the general population, 39.1% of participants reported sunbed use (50.1% in women, 10.9% in men). Sunbed use was the only relevant RF more predominant in women than men, favoring the trend to female predominance of BCCs above other RF. Additionally, we found a significant trend in young participants for reduced sunbed use (P<0.001), although they had the same percentage of repeated sunburns. Repeated sunburns are the most relevant RF for early-onset BCCs that can be targeted in prevention campaigns. We should be aware of the more relevant RF for early-onset BCCs and their distribution among the general population to address preventive campaigns.

Early-Onset Basal Cell Carcinoma; Wide Case Series At A Single Tertiary Center In Middle Anatolia

OBJECTIVEAlthough basal cell carcinoma (BCC) is prevalent in the older population, it can be rarely seen in younger people. This study aims to investigate the risk factors and characteristics of BCC in young patients.METHODSPathology reports in a single tertiary care institution between 2010 and 2020 were retrospectively reviewed. Patients under the age of 35 who were diagnosed with BCC were included for the analysis. Data were gathered from medical records and pathology reports. Demographic characteristics, accompanying pathologies, and clinical findings of these patients were analyzed.RESULTSThere were a total of 32 patients in our cohort. Out of 32 patients, 20 were female and 12 were male. One male patient and five female patients were younger than 18. An accompanying risk factor (Gorlin syndrome, XP, renal transplantation, etc.) was present in six patients. There were no known additional diseases or risk factors in 26 patients. Metastasis and recurrence were not reported in any of our patients. Contrary to the information in the literature, the patients with BCC at a young age were not found more aggressive in our study.CONCLUSIONContrary to the information in the literature, the patients with BCC at a young age were not found more aggressive in our study. Understanding the risk factors associated with BCC is essential for designing prevention strategies and favoring early diagnosis. Awareness of early-onset BCC aids in early diagnosis and treatment of the disease. Therefore, BCC should be in the differential diagnosis of skin lesions in the young population. In addition, when we encounter early-onset BCC, we should not forget the accompanying risk factors and syndromes.

Cosmetic Tattooing and Early Onset Basal Cell Carcinoma: A Population-based Case-Control Study from New Hampshire.

Cosmetic tattoos use dyes with carcinogenic potential. Skin cancers arising in tattoos have been reported. We investigated whether risk of early onset basal cell carcinoma was related to the site and colors of cosmetic tattoos as part of a population-based case-control study of cases (ages 25-50 years), identified from a state-wide surveillance system, and age- and gender-matched controls, selected from driver's license records, randomly assigned an anatomic site of the cases. One hundred fifty-six cases (17%) with early onset basal cell carcinoma and 213 controls (26%) reported cosmetic tattoos. Among those with tattoos, the adjusted odds ratio of basal cell carcinoma at the tattoo site compared to another site was 1.8 (95% confidence interval = 1.0, 3.2). We observed the strongest associations for yellow and green tattoo colors. Our preliminary findings support the possibility of an enhanced risk of early onset basal cell carcinomas at the site of cosmetic tattoos.

Early-Onset Basal Cell Carcinoma in Young Female Endurance Athletes: A Report of Three Cases

No abstract available.

Early-Onset Basal Cell Carcinoma in Young Female Endurance Athletes: A Report of Three Cases

No abstract available.

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

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). To identify predictors of TD. 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. 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. Increased knowledge of those at risk for TD will allow appropriate interventions to be designed.

Body mass index, height and early-onset basal cell carcinoma in a case-control study

IntroductionBasal cell carcinoma (BCC) is the most common malignancy in the US. Body mass index (BMI) and height have been associated with a variety of cancer types, yet the evidence regarding BCC is limited. Therefore, we evaluated BMI and height in relation to early-onset BCC (under age 40) and explored the potential role of ultraviolet (UV) radiation exposure and estrogen-related exposures in the BMI-BCC relationship. MethodsBCC cases (n=377) were identified through a central dermatopathology facility in Connecticut. Control subjects (n=389) with benign skin conditions were randomly sampled from the same database and frequency matched to cases on age (median=36, interquartile range 33–39), gender, and biopsy site. Participants reported weight (usual adult and at age 18), adult height, sociodemographic, phenotypic, and medical characteristics, and prior UV exposures. We calculated multivariate odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression models. ResultsAdult BMI was inversely associated with early-onset BCC (obese vs. normal OR=0.43, 95% CI=0.26–0.71). A similar inverse association was present for BMI at age 18 (OR=0.54, 95% CI=0.34–0.85). Excluding UV exposures from the BMI models and including estrogen-related exposures among women only did not alter the association between BMI and BCC, indicating limited mediation or confounding. We did not observe an association between adult height and BCC (OR per cm=1.00, 95% CI=0.98–1.02). ConclusionsWe found a significant inverse association between BMI and early-onset BCC, but no association between height and BCC. This association was not explained by UV exposures or estrogen-related exposures in women.

The clinical and histopathological characteristics of early-onset basal cell carcinoma in Asians.

Basal cell carcinoma (BCC) is by far the most common cancer in white populations. In addition, recent reports have demonstrated an increasing incidence of BCC in Korea. We have observed a significant number of early-onset BCC cases in which the disease occurred in patients younger than 50 years. To investigate the clinicopathological characteristics of early-onset BCC in an Asian population, specifically in Koreans. One hundred and five patients with early-onset BCC were enrolled from a total of 1047 BCC patients who underwent surgery between January 1997 and December 2014 (942 patients over the age of 50 years were designated as the control group). Early-onset BCC accounted for 10.03% of all 1047 cases and the incidence over time displayed an incremental trend. The early-onset group displayed similar results as the control group, with a predominance of female BCC patients and the majority of tumours displaying the following characteristics: small in size, occurring in sun-exposed areas and belonging to the noduloulcerative clinical subtype and nodular histopathological subtype. In comparison with a previous study in a Western population, the incidence of the disease in non-exposed areas of the body, as well as the proportion of tumours of the superficial histological subtype, were lower in Asian patients. Although the clinicopathological characteristics of BCC are well-known, these characteristics have not been determined for early-onset BCC in an Asian population. Therefore, this study is the first report on early-onset BCC in Asians, specifically in a Korean patient group.

Sex hormones and the risk of keratinocyte cancers among women in the United States: A population-based case-control study.

Men are at a higher risk of developing both squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) than women, but there is emerging evidence that women may be experiencing greater increases in the incidence rates of these malignancies than men. One possible explanation is the expanding use of sex steroids among women, although only a few studies have examined this hypothesis. As part of a population-based, case-control study of women in New Hampshire, USA, we sought to evaluate the risk of SCC, BCC, and early-onset BCC in relation to exogenous and endogenous sex hormones. We found that oral contraceptive (OC) use was associated with an increased risk of SCC (OR = 1.4, 95% CI = 1.1-1.8) and BCC (OR = 1.4, 95% CI = 1.0-1.8), particularly high estrogen dose (>50 mg) OC use. Hormone replacement therapy (HRT) use also related to SCC, with an elevated OR largely for progestin use (OR = 1.4, 95% CI = 1.1-1.8). Additionally, both OC use and combination HRT use were associated with more aggressive BCC subtypes. In contrast, menstrual and reproductive history did not appear to influence keratinocyte cancer risk in our data. Our findings provide evidence that use of sex steroids may enhance risk of keratinocyte cancer.

Tanning bed exposure and multiple early-onset basal cell carcinoma

Tanning bed exposure and multiple early-onset basal cell carcinoma

Distinct Histologic Subtypes and Risk Factors for Early Onset Basal Cell Carcinoma: A Population-Based Case Control Study from New Hampshire

Distinct Histologic Subtypes and Risk Factors for Early Onset Basal Cell Carcinoma: A Population-Based Case Control Study from New Hampshire

Abstract A50: Impact of indoor tanning and MC1R genotype on basal cell carcinoma risk in young people

Abstract Background: The incidence of basal cell carcinoma (BCC), which accounts for the majority of non-melanoma skin cancer (NMSC), is increasing, particularly in young people. While BCC is treatable, it can be associated with significant morbidity and health care costs. The ability to identify individuals at the highest risk of early-onset BCC could help focus public health efforts and mitigate the increasing incidence. However, to date, few risk prediction models exist for BCC. To identify individuals at risk of BCC at young ages, we assessed the utility of existing skin cancer risk prediction models (for melanoma or overall skin cancer) in the setting of early-onset BCC and built a novel risk prediction model, with a focus on indoor tanning and melanocortin 1 receptor (MC1R) genotype. Methods: We evaluated unconditional multivariate logistic regression models among 759 (376 cases, 383 controls) non-Hispanic whites from the Yale Study of Skin Health, a case-control study of early-onset BCC conducted in Connecticut among individuals under age 40. BCC cases and randomly sampled controls with minor benign skin conditions diagnosed between July 2006 and September 2010 were identified through Yale University's Dermatopathology database. Participants completed a structured in-person interview, self-administered questionnaires, and provided a saliva sample. We gathered self-reported eye color, skin color (inner upper arm), hair color (natural color), freckling on the arms (based on images), number of moles on the back ≥ 5 mm (clear acetate size template), mole removal, skin reaction to sunlight for the first time in the summer for one hour without sunscreen, skin reaction after repeated and prolonged exposure to sunlight, family history of melanoma and NMSC, and indoor and outdoor ultraviolet (UV) radiation exposure. We assessed the predictive performance of our novel risk prediction model and two models in the literature via summary measures of calibration, misclassification, and discrimination. We employed bootstrapping to better reflect the area under the receiver operating characteristic curve (AUC) expected when the model is tested on an independent, but similar set of patients. To investigate if indoor tanning and MC1R improved prediction performance over our early-onset BCC base model, we evaluated the regression coefficients for the markers in the expanded risk model and the corresponding likelihood ratio test statistic. All statistical tests were two-sided and analyses were performed in the statistical software R (Version 3.0.2). Results: An existing model by Han et al. (2006) included seven MC1R variants and in our data the bootstrapped AUC for this model was 0.72 (95% CI, 0.66-0.78). Another existing model by Smith et al. (2012) with MC1R and indoor tanning resulted in a bootstrapped AUC of 0.69 (95% CI 0.63-0.75) in our population. Our base model, which included hair color, skin color, skin reaction with prolonged sun exposure, education, freckles on arm, family history of NMSC, and outdoor sun exposure in warm months, had greater predictive ability (bootstrapped AUC=0.75, 95% CI=0.72-0.79) than the existing models we evaluated. We also found that our model was significantly improved when we added ever indoor tanning, burns from indoor tanning, and the R151C MC1R variant (bootstrapped AUC=0.77, 95% CI, 0.74-0.81). Conclusions: Our risk prediction model incorporating both MC1R and indoor tanning in the risk of early-onset BCC, validates and extends the work of other skin cancer risk prediction models and emphasizes the value of considering both genotype and indoor tanning in skin cancer risk prediction in young people. Therefore, in addition to the typical skin cancer characteristics clinicians rely on, assessing and counseling young people to reduce both indoor and outdoor UV exposure is needed to reduce BCC risk. Citation Format: Annette M. Molinaro, Leah M. Ferrucci, Brenda Cartmel, Erikka Loftfield, David J. Leffell, Allen E. Bale, Susan T. Mayne. Impact of indoor tanning and MC1R genotype on basal cell carcinoma risk in young people. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A50.

Family history of skin cancer is associated with early-onset basal cell carcinoma independent of MC1R genotype

BackgroundAs a marker of genetic susceptibility and shared lifestyle characteristics, family history of cancer is often used to evaluate an individual’s risk for developing a particular malignancy. With comprehensive data on pigment characteristics, lifestyle factors, and melanocortin 1 receptor (MC1R) gene sequence, we sought to clarify the role of family history of skin cancer in early-onset basal cell carcinoma (BCC). Materials and methodsEarly onset BCC cases (n=376) and controls with benign skin conditions (n=383) under age 40 were identified through Yale dermatopathology. Self-report data on family history of skin cancer (melanoma and non-melanoma skin cancer), including age of onset in relatives, was available from a structured interview. Participants also provided saliva samples for sequencing of MC1R. ResultsA family history of skin cancer was associated with an increased risk of early-onset BCC (OR 2.49, 95% CI 1.80–3.45). In multivariate models, family history remained a strong risk factor for early-onset BCC after adjustment for pigment characteristics, UV exposure, and MC1R genotype (OR 2.41, 95% CI 1.74–3.35). ConclusionsRisk for BCC varied based upon the type and age of onset of skin cancer among affected relatives; individuals with a first-degree relative diagnosed with skin cancer prior to age 50 were at highest risk for BCC (OR 4.79, 95% CI 2.90–7.90). Even after taking into account potential confounding effects of MC1R genotype and various lifestyle factors that close relatives may share, family history of skin cancer remained strongly associated with early-onset BCC.

Indoor tanning and the MC1R genotype: risk prediction for basal cell carcinoma risk in young people.

Basal cell carcinoma (BCC) incidence is increasing, particularly in young people, and can be associated with significant morbidity and treatment costs. To identify young individuals at risk of BCC, we assessed existing melanoma or overall skin cancer risk prediction models and built a novel risk prediction model, with a focus on indoor tanning and the melanocortin 1 receptor gene, MC1R. We evaluated logistic regression models among 759 non-Hispanic whites from a case-control study of patients seen between 2006 and 2010 in New Haven, Connecticut. In our data, the adjusted area under the receiver operating characteristic curve (AUC) for a model by Han et al. (Int J Cancer. 2006;119(8):1976-1984) with 7 MC1R variants was 0.72 (95% confidence interval (CI): 0.66, 0.78), while that by Smith et al. (J Clin Oncol. 2012;30(15 suppl):8574) with MC1R and indoor tanning had an AUC of 0.69 (95% CI: 0.63, 0.75). Our base model had greater predictive ability than existing models and was significantly improved when we added ever-indoor tanning, burns from indoor tanning, and MC1R (AUC = 0.77, 95% CI: 0.74, 0.81). Our early-onset BCC risk prediction model incorporating MC1R and indoor tanning extends the work of other skin cancer risk prediction models, emphasizes the value of both genotype and indoor tanning in skin cancer risk prediction in young people, and should be validated with an independent cohort.

History of allergy and atopic dermatitis in relation to squamous cell and Basal cell carcinoma of the skin.

Little is known about whether history of allergies and atopy is related to the occurrence of keratinocyte cancers. Thus, we evaluated the association between history of allergies and atopy and the incidence of squamous cell carcinoma (SCC) and early onset basal cell carcinoma (BCC). As part of a population-based case-control study, interviews were conducted with 1,050 residents of New Hampshire (375 early onset BCC cases and 251 controls, 254 SCC cases and 432 controls). ORs of SCC and early onset BCC and history of allergy and atopic dermatitis were computed using logistic regression, while controlling for potential confounding factors. An overall inverse association was observed between a history of allergy and early onset BCC [OR, 0.61; 95% confidence interval (CI), 0.38-0.97] but not SCC (OR, 1.18; 95% CI, 0.78-1.79). Among women, we found reduced ORs of both early onset BCC and of SCC in relation to allergy history (early onset BCC OR, 0.53; 95% CI, 0.31-0.92 and SCC OR, 0.59; 95% CI, 0.29-1.19). Among men, we observed no clear association with early onset BCC (OR, 0.87; 95% CI, 0.39-1.99) and an increased risk of SCC (OR, 1.58; 95% CI, 0.93-2.69). Our findings suggest that allergies and atopy may influence risk of early onset BCC and SCC, and that effects may be gender specific. A deeper understanding of the immune mechanisms underlying allergies and atopy may provide new routes of preventing keratinocyte cancers.

Melanoma of unknown primary origin coexisting with early-onset multifocal basal cell carcinoma.

Melanoma of unknown primary origin coexisting with early-onset multifocal basal cell carcinoma.

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

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. To evaluate alcohol intake in relation to early-onset BCC, and explore potential interactions with UV exposure. 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. 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. Overall, we did not observe any clear association between lifetime alcohol intake and early-onset BCC.

Common variants modify the age of onset for basal cell carcinomas in Gorlin syndrome.

Gorlin syndrome is an autosomal dominant disorder, characterized by multiple early-onset basal cell carcinomas (BCCs) and jaw keratocysts. Through association studies in cohorts of sporadic BCC, nine genetic variants have previously been identified to increase the risk of BCC. The nine SNPs were genotyped by Taqman allelic discrimination in 125 individuals with Gorlin syndrome. Kaplan-Meier survival curves and Cox proportional-Hazard regression analysis were applied to determine the association between genotypes and age of first BCC in individuals with Gorlin syndrome. The p.(Arg151Cys) variant in MC1R (rs1805007) was associated with an earlier median age of onset of BCC of 27 years (95% CI: 20-34) compared with 34 years (95% CI: 30-40) for wild-type individuals (hazard ratio (HR)=1.64, 95% CI: 1.04-2.58, P=0.034). The risk allele of the variant at the chromosome 5p15 locus encompassing TERT-CLPTM1L (rs401681) was also associated with an earlier median onset of BCC, 31 years (95% CI: 28-37) compared with 41 years (95% CI: 32-48, HR=1.44, 95% CI: 1.08-1.93, P=0.014). In individuals with a risk allele at either rs1805007 or rs401681 the median time to BCC was 31 years of age (95% CI: 28-34) compared with 44 years of age (95% CI: 38-53) in wild-type individuals (HR=2.48, 95% CI: 1.47-4.17, P=0.0002). Our findings may have implications for future personalized risk estimates and BCC screening strategies in individuals with Gorlin syndrome.