Risk Factors For Basal Cell Carcinoma Research Articles

Association between cathepsins and skin cancers: A bidirectional two-sample Mendelian randomization study.

Several cathepsins have been identified as being involved in the development of cancer. Nevertheless, the connection between cathepsins and skin cancers remained highly elusive. A bidirectional Mendelian randomization (MR) analysis was performed to investigate the causal association between cathepsins and skin malignancies. The genome-wide association studies (GWAS) data for cathepsins, malignant melanoma (MM), and basal cell carcinoma (BCC) were obtained from European research. The primary method employed was inverse variance weighted. In addition, MR-Egger, weighted median, weighted mode, and simple mode were also executed. Sensitivity analysis was performed using Cochran's Q test, MR-Egger, and MR-PRESSO. From univariable MR (UVMR), cathepsin H, and S were determined to have a causal relationship with BCC. Additionally, cathepsin H was identified as associated with MM. Multivariable MR (MVMR) showed that after correcting for risk factors of skin carcinoma, cathepsin H was detected to be protective against BCC, whereas cathepsin S has been observed as a risk factor for BCC. No substantial pleiotropy and heterogeneity were identified in the sensitivity analysis. This study was the first to establish a direct link between cathepsins and skin malignancies. Cathepsin H and S have the potential to serve as new biomarkers for BCC, offering valuable assistance in the prompt identification, treatment, and prevention of the disease. Nevertheless, additional clinical trials are required to validate our findings.

Assessment of sun-related behavior and serum vitamin D in basal cell carcinoma: Preliminary results.

Ultraviolet radiation (UV), mainly from sunlight, is the main risk factor of the most common human skin cancer, basal cell carcinoma (BCC). A positive effect of UV on the skin is its contribution to the synthesis of vitamin D, which is important in sustaining general health, but having high levels of vitamin D is considered a risk factor for BCC. However, vitamin D receptor has antagonistic effects to UV radiation in regulating Sonic Hedgehog pathway. This is a pilot study aimed at characterizing the sun-related behavior and vitamin D status of 52 BCC patients and 59 controls from our geographical area. Patients were included in 4 subgroups: Single, multiple, recurrent, and both multiple and recurrent BCCs. Patients, more than controls, had at least one sunburn in childhood and lentigines (P<0.001). Also, they spent daily, on average, more time in the sun than controls (P<0.001) (3.00-8.00 and 1.50-4.00 h respectively). Outdoor work was similar in both groups. Participants had lower vitamin D serum levels than expected. Due to the small number of cases, no statistically significant differences were found between the subgroups but some tendencies were noted. Patients with only one recurrent BCC had less sunburns than the ones who also developed tumors at multiple sites (P=0.2). Patients with multiple and recurrent tumors had slightly lower vitamin D levels compared with single BCC patients (P=0.1) although they used more vitamin D supplements after the BCC diagnosis (P=0.2). Having a diagnosis of BCC, made patients more compliant to the use of sunscreen cream, but even so, half of them still did not use it. In conclusion, more effort should be invested in sun-related education and public health actions should focus on vitamin D deficiencies.

Basal Cell Carcinoma Risk and TP53 Arg72Pro Polymorphism: An Algerian Population Study

Background: Basal cell carcinoma (BCC) is the commonest skin cancer in human. It is characterized by a strictly local malignity with a frequent tendency to relapse. BCC development results from the interaction between environmental factors and genetic alterations, including mutations in the TP53 gene involved in its progression and relapse. TP53 gene is named “guardian of the genome”, as it plays major roles in genomic stability. In addition to mutations, several polymorphisms had been detected in the wild-type TP53. The polymorphic variant is usually associated to BCC diseases at codon 72 of TP53 (Arg72Pro). Objectives: In the present study, we undertook a case control study to explore a possible association between TP53 Arg72Pro polymorphism and the predisposition to BCC in Northwest Algerian population. Methods: TP53 Arg72Pro polymorphism was investigated by PCR/RFLP then confirmed by DNA sequencing of 61 controls versus 50 BCC cases. Results: This study allows us to characterize BCC subgroups regarding age, tumor location, and relapse. No correlation was found between any of these criteria and each of the two variants of TP53 Arg72Pro. No association was found between TP53 Arg72Pro variants and developing BCC either (BCC group: Pro = 54%, versus Control group: Pro = 53 %, P > 0.05, OR 1.52 (0.89 - 2.60)). Finally, as expected, sun-exposure was confirmed as a risk factor for BCC. Conclusions: This study supports that analyzing TP53 Arg72Pro polymorphism is of no interest for identifying high-risk subjects for BCC in the Algerian population. Further studies are needed to explain the role of this polymorphism in genetic predisposition to BCC in some other populations.

A prospective study of cigarette smoking and basal cell carcinoma.

To investigate the relationship between smoking and primary basal cell carcinoma (BCC), we analyzed data from a 16year prospective study among randomly selected adults in Nambour, Queensland, Australia. Participants underwent a skin examination in 1992 and took part in an intervention study and follow-up. Information about complexion type and smoking habits including duration and number of cigarettes smoked per day and sun exposure behavior were collected at baseline in 1992, with updates to end of follow-up in 2007. Newly-diagnosed BCCs were ascertained from regional pathology laboratories. Relative risks (RR) of BCC among former and current smokers were estimated using generalized linear models specifying a Poisson distribution with robust error variance and (log) person-years at-risk as offset, adjusting for BCC risk factors. From 1992 to 2007, 281 BCCs were diagnosed in 1,277 participants with available smoking history and no past BCC. Relative to non-smokers, a non-significant inverse association between current smoking and BCC was seen (RR 0.69; 95% CI 0.45-1.05) but not for former smokers (RR 1.05; 95% CI 0.84-1.31). Amongst current smokers, inverse associations with BCC were found in those who smoked for up to 18years (RR 0.44) but not more and those who smoked up to 15 cigarettes per day but not more. The associations with both current and former smoking varied by degree of sunburn propensity. The modest inverse association between current smoking and BCC is considered unlikely to be causal given lack of clear relation with duration or intensity of smoking.

Update of the European guidelines for basal cell carcinoma management.

European guidelines for the management of basal cell carcinoma (BCC) prepared by the former BCC subcommittee of the Guidelines Committee of the European Dermatology Forum (EDF) were published in 2006. To present updated guidelines that include consensual expert definitions on various BCC types, prognosis and risk factors for BCC as well as review recommendations for diagnosis and treatment reflecting current published evidence. These guidelines (S1 type) were prepared by the new BCC subgroup of the European Dermatology Forum (EDF)'s Guidelines Committee through extensive literature review (up to 2012) and expert experience; they were extensively discussed within the EDF subcommittee and approved by peer reviewers of the EDF. Results BCC is a common tumour with an incidence rising worldwide. Three major clinical types of BCC are recognized: nodular, superficial and morpheaform. Four histological subtypes are defined: superficial, nodular, infiltrative and morpheaform. On the basis of the risk of relapse, three prognosis groups have been identified: high, intermediate and low risk. According to these classifications and evidence-based evaluation of the therapeutic strategies available, a decision tree is proposed for the management of BCCs. The guidelines offer a useful tool that will help dermatologists to select the most appropriate treatment for individual patients.

Predictors of Basal Cell Carcinoma in High-Risk Patients in the VATTC (VA Topical Tretinoin Chemoprevention) Trial

Basal cell carcinoma (BCC) is the most common cancer in the United States today, and patients who have had one are likely to have multiple carcinomas over time. Predictors of new BCCs on the face and ears among those at very high risk have not been studied in detail. We sought to do so prospectively in the context of a 6-year trial. We found that the number of BCCs in the prior 5 years was the most important predictor. Age, sun sensitivity, occupational sun exposure before the age of 30 years (but not afterward), lower educational level, history of eczema, the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and more sunscreen use in the week, but not the 6 months, before enrollment were also independent predictors, but sunburns, baseline sun exposure, and other sun-protective measures, other skin cancers, and actinic keratoses were not. None of the eczema patients had a history of topical calcineurin use. The cumulative risk of BCC was 55% at 5 years. These findings document the key risk factors in this very high-risk population, suggesting that the history of eczema may increase the risk in those at high risk and that early sun exposure is important even in this group, and underscoring the need for chemopreventive strategies.

Risk factors for basal cell carcinoma in a southern Brazilian population: a case–control study

Basal cell carcinoma (BCC) is the most common cancer to occur in Caucasian populations, and its incidence is increasing. Despite its frequency, there is a paucity of data on risk factors for BCC in some regions. This study investigated the association between pigmentary characteristics, distinctive patterns of solar exposure, habits and lifestyle, and risk for BCC among patients attending a dermatology center in a region in southern Brazil. We conducted a hospital-based, case-control study that included 127 case patients with histologically confirmed BCC and 280 cancer-free control subjects with other dermatologic conditions, observed between January 2006 and December 2007. The study was conducted using a questionnaire and physical examination by a dermatologist. Relative risks were estimated using exposure odds ratios generated by cross-tabulation and logistic regression models. Risk for BCC was associated with family history of skin cancer, Fitzpatrick skin type I, and the presence of actinic keratoses, solar lentigines, leukoderma, and elastosis romboidalis nuchae. No effect was found for different patterns of solar exposure, eye, hair or skin color, exposure to non-solar ultraviolet radiation (UVR), or lifestyle-related habits such as sunscreen use and cigarette smoking. The results of this study suggest that skin type and family history of skin cancer may be important in establishing risk for developing BCC. Additionally, the detection by clinical examination of skin markers related to UVR action is important in establishing which patients are more likely to develop BCC.

Interaction between functional polymorphic variants in cytokine genes, established risk factors and susceptibility to basal cell carcinoma of skin

Basal cell carcinoma (BCC) of the skin is the most common neoplasm among the Caucasian population of the Western world. Inflammation may result in oxidative stress and contribute to promotion and progression of tumors, including BCC. The role of cytokines, which are inflammatory modulators, in the biology of tumors has been extensively studied and it is well known that they are aberrantly produced by cancer cells, macrophages and other phagocytic cells. Genetic polymorphisms are known in several cytokine genes, which result in altered expression. In the present association study, we investigated the association of 14 functional polymorphisms in 11 cytokines genes with BCC risk in 529 BCC cases and 532 healthy controls. We have also tested the possible interactions between the genetic variants and three known risk factors for BCC: skin complexion, sun effect and skin response to sun exposure. We did not observe any statistically significant association between SNPs and BCC risk. However, we found that, in a subgroup of subjects more prone to skin burns, carriers of at least one copy of the G allele of rs1800629 (TNF) had an increased risk of BCC [odds ratio (OR) = 2.40, 95% confidence interval (CI) 1.38-4.16, P = 0.0005]. Moreover, in subjects less prone to sunburns, we observed that carriers of the C allele of rs1143627 (IL1B) showed a decreased risk (OR = 0.53, 95% CI 0.34-0.82, P = 0.0019). In conclusion, we found that two polymorphisms in inflammatory genes interacting with environmental risk factors could modulate BCC risk.

Use of nonsteroidal anti-inflammatory drugs and risk of basal cell carcinoma in the United States radiologic technologists study

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with reduced risk of colorectal and other cancers, but the association with basal cell carcinoma (BCC) is unclear. Previous epidemiological studies have been small in size, conducted in especially vulnerable populations, or have not accounted for solar ultraviolet exposure, a major risk factor for BCC. In the United States Radiologic Technologists cohort, we followed subjects to assess NSAID use on risk of first incident BCC. We included Caucasian participants who responded to both second and third questionnaires (administered from 1994 to 1998 and 2003 to 2005, respectively), and who reported no cancer at the time of the second questionnaire, N = 58,213. BCC, constituent risk factors (e.g., eye color, complexion, hair color) and sun exposure history were assessed through self-administered survey. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Of the 58,213 people in the study population, 2,291 went on to develop BCC. Any NSAID use was not associated with subsequent incidence of BCC (HR = 1.04, 95% CI: 0.92-1.16) after adjusting for age, sex and estimated lifetime summer sun exposure. Neither association was observed when stratified by NSAID type (aspirin and other NSAIDs), nor did dose-response patterns emerge by frequency of use (average days per month). Further analyses did not reveal interaction with sex, birth cohort, smoking, alcohol consumption, sun exposure, occupational radiation exposure or personal risk factors for BCC. In this large nationwide study, we observed no association between NSAID use and subsequent BCC risk.

POMC and TP53 genetic variability and risk of basal cell carcinoma of skin: Interaction between host and genetic factors

Basal cell carcinoma (BCC) of the skin is the most common neoplasm among the Caucasian population of the western world. Ultraviolet (UV) radiation-induced p53 activation promotes cutaneous pigmentation by increasing transcriptional activity of pro-opiomelanocortin (POMC) in the skin. Induction of POMC/α-melanocyte-stimulating hormone (α-MSH) activates the melanocortin 1 receptor (MC1R), resulting in skin pigmentation. The tumor suppressor p53 is a key player in stress responses that preserve genomic stability, responding to a variety of insults including DNA damage, hypoxia, metabolic stress and oncogene activation. Malfunction of the p53 pathway is an almost universal hallmark of human tumors. Polymorphisms in the gene encoding p53 (TP53) alter its transcriptional activity, which in turn may influence the UV radiation-induced tanning response. The aim of the present work is to test association between POMC and TP53 genetic variability, the possible interplay with host factors and the risk of basal cell carcinoma of skin. We covered the variability of the two genes we used 17 tagging polymorphisms in 529 BCC cases and 532 healthy controls. We have also tested the possible interactions between the genetic variants and three known risk factors for BCC: skin complexion, sun effect and skin response to sun exposure. We did not observe any statistically significant association between SNPs in these two genes and BCC risk overall, nor interactions of SNPs with known BCC risk factors. However we found that, in the group of subjects with lower sun exposure, carriers of one copy of the C allele of the TP53 SNP rs12951053 had a decreased risk of BCC (OR=0.28, 95% CI 0.12-0.62, P=0.002). We have observed that the interplay of an environmental risk factor and one polymorphism in TP53 gene could modulate the risk of BCC.

Common variants on 1p36 and 1q42 are associated with cutaneous basal cell carcinoma but not with melanoma or pigmentation traits

To search for new sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conducted a genome-wide SNP association study of 930 Icelanders with BCC and 33,117 controls. After analyzing 304,083 SNPs, we observed signals from loci at 1p36 and 1q42, and replicated these associations in additional sample sets from Iceland and Eastern Europe. Overall, the most significant signals were from rs7538876 on 1p36 (OR = 1.28, P = 4.4 x 10(-12)) and rs801114 on 1q42 (OR = 1.28, P = 5.9 x 10(-12)). The 1p36 locus contains the candidate genes PADI4, PADI6, RCC2 and ARHGEF10L, and the gene nearest to the 1q42 locus is the ras-homolog RHOU. Neither locus was associated with fair pigmentation traits that are known risk factors for BCC, and no risk was observed for melanoma. Approximately 1.6% of individuals of European ancestry are homozygous for both variants, and their estimated risk of BCC is 2.68 times that of noncarriers.

Risk Factors for Histological Types and Anatomic Sites of Cutaneous Basal-Cell Carcinoma: An Italian Case–Control Study

Different clinico-pathologic subtypes and anatomic sites of basal-cell carcinoma (BCC) may display distinct characteristics and mechanisms of development. However, scanty information exists on potential differences in etiological factors for BCC according to histotype and anatomic location. Thus, we analyzed data from an Italian case-control study, including 528 subjects with newly diagnosed, histologically confirmed BCC and 512 controls admitted to the same hospitals with acute conditions. The multivariate odds ratio (OR) of nodular (OR=1.53) but not superficial (OR=0.71) BCC was increased for occupational exposure to sunlight. Considering the anatomic site of BCC, the corresponding values were 1.46 for head/neck and 0.74 for truncal location. Direct associations were observed with recreational sunlight exposure, eye color, red hair, and number and early age of severe sunburn episodes, along with some differences in risk between histotypes and anatomic sites. This study confirmed the role of (intermittent) sun exposure and phenotypic characteristics as risk factors for BCC, and suggested etiological differences between nodular and superficial histotypes and between head/neck and truncal locations.

Pigmentary and cutaneous risk factors for non‐melanocytic skin cancer—A case‐control study

The roles of ethnic origin, pigmentary traits, sun sensitivity and other cutaneous characteristics as risk factors for basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) were examined in a case-control study of prevalent and incident cases of histopathologically confirmed skin cancers. Two hundred and twenty six confirmed cases of BCC, 45 of SCC and 1,015 controls with no lesions were identified in a population-based survey of skin cancer in 1987 in Geraldton, Western Australia. The risk of both cancers was higher in native-born Australians than in migrants. The risk of BCC decreased with increasing age at arrival in Australia. Southern European ancestry was strongly protective against BCC (for any southern European grandparents) and SCC (no case of SCC had any grandparents of southern European origin). Inability to tan was the strongest pigmentary risk factor for both BCC and SCC. Among factors that incorporated a measure of sun exposure as well as sun sensitivity, freckling on the arm in childhood was important for both cancers, the number of moles on the back was important for BCC, and forearm skin colour and having a permanent colour difference between the neck and adjacent protected areas were important for SCC. Among measures of sun damage to the skin, solar elastosis of the neck was a strong risk factor for both BCC and SCC, loss of fine texture of the skin of the back of the hands (as measured by cutaneous microtopography) was important for BCC and telangiectasia of the face for SCC. When all important variables for each cancer were examined together in a single model with age, sex, migrant status or age at arrival in Australia, and ethnicity, in ability to tan, solar elastosis of the neck, and the number of moles on the back were independently significant risk factors for BCC and solar elastosis of the neck and having a permanent colour difference between the neck and adjacent protected areas were independently significant risk factors for SCC. The effects of age at arrival or migrant status and ethnic origin remained important in the models incorporating these factors. A history of ever having acne and a history of warts were protective for BCC and a history of acne was protective for SCC.