Reduced incidence of skin cancer in patients with alopecia areata: A retrospective cohort study

The risk of skin cancer in patients with alopecia areata (AA) is unknown. While the risk of skin cancer in chronic inflammatory alopecias may be elevated, AA shares many characteristics with vitiligo, an autoimmune illness associated with decreased risk of melanoma and non-melanoma skin cancers. In this retrospective cohort study, we determined the risk of developing skin cancer among patients with AA in a validated cohort relative to matched controls at two tertiary care hospitals in Massachusetts. There was a significantly decreased risk of NMSC in AA patients than controls (OR = 0.63, 95% CI = 0.48–0.81). There was a trend towards a protective effect of AA associated with melanoma (OR = 0.65, 95% CI = 0.39–1.09). There was no difference in anatomic distribution of skin cancer between patients with AA and controls. Our study demonstrates a decreased risk of nonmelanoma skin cancer and a trend towards reduced risk of melanoma in patients with AA.     

Long-term health risk to the skin of ultraviolet radiation

The major well-proven long-term health risks of excessive exposure to ultraviolet (UV) radiation relate to the skin. Premalignant skin lesions are seen very much earlier in white skinned populations exposed to excessive sunlight, and over time these same individuals develop larger numbers of all of the three major skin cancers than individuals who do not experience excessive UV exposure. These three skin cancers are squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and malignant melanoma. In the case of SCC the major aetiological pattern is chronic long-term exposure, but for BCCs the pattern appears to be slightly different with short-term burning episodes being more important. In the case of melanomas, there is evidence that for the 4 main types of melanomas, the pattern of excess UV exposure which is most injurious varies.     

A meta-analysis of second cancers after a diagnosis of nonmelanoma skin cancer: additional evidence that solar ultraviolet-B irradiance reduces the risk of internal cancers

BACKGROUND: Nearly 20 types of cancer have been found to be inversely correlated with solar ultraviolet-B (UVB) levels determined geographically in ecologic studies, assuming that personal solar UVB irradiances were directly related to July solar UVB doses. This assumption has been questioned. METHODS: Rates of second cancer after diagnosis of nonmelanoma skin cancer (NMSC) from the literature were used in linear regression analyses. The risk modification of NMSC due to smoking was accounted for by comparing second cancer risk ratios (RRs) with lung cancer RRs in regression analysis for each cancer. RESULTS: For a diagnosis of squamous cell carcinoma, RRs for subsequent colon, gastric, and rectal cancers were significantly reduced, with that for renal cancer being marginally insignificant. For NMSC, RRs for cervical, esophageal, gastric, and rectal cancer were significantly reduced; those for colon and gallbladder cancer were marginally insignificant, while those for female breast, laryngeal, ovarian, renal, and uterine corpus cancers were insignificantly reduced; RRs for lip and salivary gland cancers and melanoma were significantly increased. Melanoma was inversely correlated with lung cancer. CONCLUSION: These results provide nearly direct evidence that solar UVB irradiance reduces the risk of many internal cancers. The likely mechanism is production of Vitamin D.     

Seasonal variation in diagnosis of cutaneous invasive melanoma and cutaneous squamous cell carcinoma: A nationwide study in the Netherlands

BackgroundCurrently, there is no study that has reported on the seasonal trends of skin cancer in the Netherlands. This study aimed to investigate seasonal variation in diagnosis of cutaneous melanoma (CM) and cutaneous squamous cell carcinoma (cSCC) focusing on different subgroups.MethodsCM diagnosed from 2001 till 2019 and cSCCs from 2001 till 2015 were selected from the Netherlands Cancer Registry. The monthly distribution of CM and cSCC diagnoses were evaluated. Summer-to-winter ratios (SWRs) were calculated overall and stratified by patient and tumour characteristics.ResultsSignificant increases in melanoma incidence were noted over the summer months (SWR 1.39 (CI 1.37–1.40)). This increase was less apparent for cSCCs, as higher incidence rates were observed in the months September-November (SWR 1.13 (CI 1.12–1.14)). The seasonal variation of CM was greater in women and younger people, in superficial spreading melanoma and lentigo maligna melanoma, for the extremities, in thinner lesions, and for stage I at diagnosis. The seasonal variation of cSCC was similar for both sexes, most marked in patients 45‐69 and ≥ 70, and for the extremities.ConclusionsOur findings showed a pronounced seasonal variation in the diagnosis of CM with a peak in the summer months. For cSCC, no evident peak was observed, but an increase in diagnosis was noted in fall. Both CM and cSCC showed strong seasonal effects for the extremities.     

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.     

Proportion of cancer cases and deaths attributable to lifestyle risk factors in Brazil

BackgroundLifestyle risk factors (tobacco smoking, alcohol consumption, overweight and obesity, unhealthy diet, and lack of physical activity) have been associated with increased risk of at least 20 types of cancer. We estimated the proportion of cancer cases and deaths that could be potentially avoided by eliminating or reducing lifestyle risk factors in Brazil.MethodsWe obtained the distribution of lifestyle risk factors by sex and age groups from recent representative health surveys in Brazil; relative risks from pooled analyses of prospective studies and meta-analyses; and cancer cases and deaths in 2012 from GLOBOCAN.ResultsWe found that 26.5% (114,497 cases) of all cancer cases and 33.6% (63,371 deaths) of all cancer deaths could be potentially avoided by eliminating lifestyle risk factors in Brazil. Plausible reductions in these exposures based on policy targets and cancer prevention recommendations could have potentially avoided 4.5% (19,731 cases) and 6.1% (11,480 deaths) of all cancer cases and deaths, respectively. Tobacco smoking accounted for most of the preventable cancer cases and deaths, followed by high body mass index and alcohol consumption. Larynx, lung, oropharynx, esophagus and colorectum cancer cases and deaths could be at least halved by eliminating these lifestyle risk factors.ConclusionFindings from this study may be useful to inform strategies for cancer prevention and control across Brazil.     

Trends in incidence and survival analysis in non-melanoma skin cancer from 1994 to 2012 in Girona,Spain: A population-based study

IntroductionWe present an epidemiological study focused on Non-melanoma skin cancers (NMSC), including squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Merkel cell carcinoma (MCC), dermatofibrosarcoma protuberans (DFS) and adnexal and skin appendages neoplasm (ASAN), a neoplasm understudied in cancer registries.Material and methodsWe analyze trends of incidence and survival of NMSC registered with the Cancer Registry of Girona, Spain.ResultsWe found 14389 cases of NMSC, accounting 3,474 SCC, 10729 BCC, 33 MCC, 61 DFSP and 71 ASAN. Incidence increased significantly in SCC and BCC with annual percentage of change of 1.6 and 1.5, respectively, but not in MCC, DFS or ASAN. Five-year relative survival for both sexes was 90.1% in SCC, 99.8% in BCC, 44.2% in MCC, 93.7% in DFS and 84% in ASAN.ConclusionsOur study confirms the increasing incidence and good survival of SCC and BCC and enhances knowledge on the epidemiology of the less incidental NMSC.     

Genome-wide association studies of pigmentation and skin cancer: a review and meta-analysis

Recent genome-wide association studies (GWAS) identified genetic loci associated with pigmentation, nevi, and skin cancer. We performed a review and meta-analysis of GWAS results, grouping them into four categories: (i) loci associated with pigmentation (hair, eye, and/or skin color), cutaneous UV-response (sun sensitivity and/or freckling), and skin cancer; (ii) loci associated with nevi and melanoma; (iii) loci associated with pigmentation and/or cutaneous UV-response but not skin cancer; and (iv) loci associated distinctly with skin cancer, mostly basal cell carcinoma, but not pigmentation or cutaneous UV-response. These findings suggest at least two pathways for melanoma development (via pigmentation and via nevi), and two pathways for basal cell carcinoma development (via pigmentation and independent of pigmentation). However, further work is necessary to separate the association with skin cancer from the association with pigmentation. As with any GWAS, the identified loci may not include the causal variants and may need confirmation by direct genome sequencing.     

沉默Gpr48基因表达对皮肤鳞状细胞癌细胞系A431 PKC信号通路活化及细胞侵袭的影响

目的分析沉默G蛋白偶联受体48 （Gpr48）基因表达对皮肤鳞状细胞癌（SCC）蛋白激酶C （PKC）信号通路及细胞侵袭能力的影响。 方法构建ShRNA感染皮肤SCC细胞株A431,设计干扰Gpr48表达shRNA（shRNA-Gpr48组）及阴性对照shRNA-NC组,采用实时定量反转录聚合酶联反应（RT-PCR）检测Gpr48相对表达量;以蛋白印迹法（Western Blot）测定PKC相关抗体蛋白表达情况,进行Transwell小室实验检测细胞侵袭能力,总结Gpr48缺失对三丙胺（TPA）刺激A431细胞株PKC活化及细胞侵袭能力的影响,为SCC靶向治疗提供参照。组间比较采用独立样本t检验。 结果qRT-PCR结果：shRNA-Gpr48组Gpr48相对表达量（0.27±0.06）低于shRNA-NC组（1.01±0.12）,差异具有统计学意义（t?= 17.441,P?< 0.01）,shRNA-Gpr48组p-PKCδ （0.463±0.035）低于shRNA-NC组（0.721±0.074）,shRNA-?Gpr48组NF-κB p65 mRNA （0.631±0.079）低于shRNA-NC组（0.834±0.102）,差异具有统计学意义（t?= 9.966、4.975,P均< 0.01）,Notch1 mRNA（0.981±0.037）高于shRNA-NC组（0.562±0.041）,差异具有统计学意义（t?= 23.991,P?< 0.01）;Western Blot结果：shRNA-Gpr48组p-PKCδ（0.221±0.034）低于shRNA-NC组（0.292±0.046）、NF-κB p65蛋白表达（0.512±0.047）低于shRNA-NC组（0.636±0.051）,差异具有统计学意义（t?= 3.925,5.653,P均< 0.01）,Notch1（0.524±0.063）高于shRNA-NC组（0.421±0.076）,差异具有统计学意义（t?= 3.299,P?< 0.01）;shRNA-Gpr48组侵袭细胞率为（35.03±1.54）﹪,低于shRNA-NC组的（51.83±2.76）﹪,差异具有统计学意义（t?= 16.809,P?< 0.01）。 结论沉默Gpr 48缺失表达可能通过抑制PKC活化,降低p-PKCδ、NF-κB p65表达,上调抑癌基因Notch1表达,抑制癌细胞增殖、侵袭。     

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

ObjectiveTo calculate pooled risk estimates of the association between pigmentary characteristics and basal cell carcinoma (BCC) of the skin.MethodsWe 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.ResultsWe 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.ConclusionsAlthough 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.     

Second primary malignancies in patients with non-melanoma skin cancer: Results from a cancer registry–based study in Emilia Romagna,north-east Italy

Backgroundprevious research on the risk of subsequent, primary non-cutaneous malignancies among patients with non-melanoma skin cancers (NMSCs) led to conflicting results. We aimed to investigate a possible link between NMSC and second primary malignancies by using the population-based data available in cancer registries.Methodsthis observational study retrospectively assessed the risk of occurrence of both synchronous and methachronous second primary tumours in a cohort of cancer patients whose first diagnosis was NMSC. The cohort came from the network of general cancer registries of the Emilia-Romagna Region, northeast Italy, in the period between 1978 and 2012, and was compared with the general population living in the same area. Two main indexes were used: i) Standardized Incidence Ratio (SIR), calculated as the ratio between the observed and the expected number of second cancers and ii) Excess Absolute Risk (EAR), expressing the absolute excess or deficit of second cancer incidence.Resultsin the period analysed (1978–2012, 72,503,157 person/years, PYs), 89,912 primary NMSC were found in 76,414 patients. Among them, 14,195 developed a second primary cancer in the subsequent 501,763 follow-up PYs. NMSC patients showed an overall SIR of 1.22 (CI 95% 1.20-1,24) and an EAR of 5.11 cases/1000 PYs (CI 95% 4.48–5.74).Conclusionsthe study results showed that NMSC patients had an increase in relative risk and, at least for some tumours, in absolute risk of developing a second cancer when compared with the general population. Genetic, environmental and personal risk factors may influence this finding.     

The EP1 subtype of prostaglandin E2 receptor: Role in keratinocyte differentiation and expression in non-melanoma skin cancer

We have previously demonstrated that the EP₁ subtype of PGE₂ receptor is expressed in the differentiated compartment of normal human epidermis and is coupled to intracellular calcium mobilization. We therefore hypothesized that the EP₁ receptor is coupled to keratinocyte differentiation. In in vitro studies, radioligand binding, RT-PCR, immunoblot and receptor agonist-induced second messenger studies demonstrate that the EP₁ receptor is up-regulated by high cell density in human keratinocytes and this up-regulation precedes corneocyte formation. Moreover, two different EP₁ receptor antagonists, SC51322 and AH6809, both inhibited corneocyte formation. SC51322 also inhibited the induction of differentiation-specific proteins, cytokeratin K10 and epidermal transglutaminase. We next examined the immunolocalization of the EP₁ receptor in non-melanoma skin cancer in humans. Well-differentiated SCCs exhibited significantly greater membrane staining, while spindle cell carcinomas and BCCs had significantly decreased membrane staining compared with normal epidermis. This data supports a role for the EP₁ receptor in regulating keratinocyte differentiation.     

Incidence trends in oesophageal cancer by histological type: An updated analysis in Sweden

BackgroundWe aimed to update incidence trends of oesophageal cancer by histological type in Sweden.MethodsUsing data from the Swedish Cancer Registry, we examined incidence trends of oesophageal cancer by histological types in individuals aged ≥50 years in 1970–2014 using log-linear joinpoint regressions.ResultsThe age-standardised incidence rate of oesophageal adenocarcinoma in men increased on average by 3.0% per year in 1970–1994, followed by a more rapid increase of 13.7% per year in 1994–2000, and a slower increase of 2.6% per year in 2010–2014. The rate of oesophageal adenocarcinoma in women increased on average by 4.2% per year during the entire period. The rate of squamous cell carcinoma generally decreased over the past 2–3 decades in both sexes.ConclusionsThe incidence of oesophageal adenocarcinoma continues to rise in Sweden, although the increase seems to have slowed down in men since 2000. The incidence of oesophageal squamous cell carcinoma is decreasing.     

Potential use of melatonin in skin cancer treatment: A review of current biological evidence

Skin cancer, particularly melanoma, is a leading cause of death worldwide. The therapeutic methods for this malignancy are not effective, and due to the side effects of these treatments, applying an appropriate alternative or complementary treatment is important. According to available data, melatonin as the main product of the pineal gland has oncostatic and antitumoral properties. Also, melatonin acts as an anti-inflammatory and reactive oxygen species inducer agent which suppresses the growth of tumors. It also has apoptosis induction characteristics through regulating signaling pathways, including heat shock protein 70, nuclear factor-erythroid 2 p45-related factor 2 and others. Thus, adding melatonin to chemo- and radiotherapy may have synergistic therapeutic effects and increase the survival time in patients with skin cancer. Few clinical studies have evaluated the efficacy of melatonin in skin cancer. Based on the related mechanisms, this review discusses about how melatonin may improve outcomes in skin cancer patients.     

Hyperuricemia and gout are associated with cancer incidence and mortality: A meta-analysis based on cohort studies

The association between hyperuricemia or gout and cancer risk has been investigated in various published studies, but their results are conflicting. We conducted a meta-analysis to investigate whether hyperuricemia or gout was associated with the cancer incidence and mortality. Linear and nonlinear trend analyses were conducted to explore the dose–response association between them. The pooled relative risk (RR) and 95% confidence interval (CI) were used to evaluate cancer risk. A total of 24 articles (33 independent studies) were eligible for inclusion. When compared participants with the highest SUA (hyperuricemia) levels and those with the lowest SUA levels, the pooled RR was 1.08 (95% CI, 1.04–1.12), it was significantly associated among males but not among females (males, RR = 1.07; 95% CI, 1.03–1.11; females, RR = 1.06; 95% CI, 0.96–1.17). Hyperuricemia increased total cancer mortality (RR = 1.15; 95% CI, 1.05–1.26), but a significant association was observed in females rather than in males (females: RR = 1.26; 95% CI, 1.09–1.45; males, RR = 1.02; 95% CI, 0.80–1.30). Linear relationships of SUA levels with overall cancer incidence (p for nonlinearity = 0.238) and overall cancer mortality (p for nonlinearity = 0.263) were identified. However, 1 mg/dL increment in SUA levels was weakly significant in overall cancer incidence (RR = 1.01; 95% CI, 1.01–1.01) but not associated with overall cancer mortality (RR = 1.01; 95% CI, 0.99–1.03). Gout was significantly associated with increased cancer incidence (RR = 1.19; 95% CI, 1.12–1.25). In conclusion, Hyperuricemia or gout was associated with higher cancer incidence and mortality. Though a potential linear relationship between them was found, we'd better treat this result with caution.     

Assessment of skin dose in breast cancer radiotherapy: on-phantom measurement and Monte Carlo simulation

AimThe main purpose of the present study is assessment of skin dose in breast cancer radiotherapy.BackgroundAccurate assessment of skin dose in radiotherapy can provide useful information for clinical considerations.Materials and methodsA RANDO phantom was irradiated using a 6 MV Siemens Primus linac with medial and tangential radiotherapy fields for simulating breast cancer treatment. Dosimetry was also performed on various positions across the fields using an EBT3 radiochromic film. Similar conditions of measurement on the RANDO phantom including field size, irradiation angle, number of fields, etc. were subsequently simulated via the Monte Carlo N-Particle Transport code (MCNP). Ultimately, dose values for corresponding points from both methods were compared.ResultsConsidering dosimetry using radiochromic films on the RANDO phantom, there were points having underdose and overdose based on the prescribed dose and skin tolerance levels. In this respect, 81.25% and 18.75% of the points had underdose and overdose, respectively. In some cases, several differences were observed between the measurement and the MCNP simulation results associated with skin dose.ConclusionBased on the results of the points which had underdose, it was suggested that a bolus should be used for the given points. With regard to overdose points, it was advocated to consider skin tolerance dose in treatment planning. Differences between the measurement and the MCNP simulation results might be due to voxel size of tally cells in simulations, effect of beam’s angle of incidence, validation time of linac’s head, lack of electronic equilibrium in the build-up region, as well as MCNP tally type.