Regular Intake of Green Tea Polyphenols Suppresses the Development of Nonmelanoma Skin Cancer through miR-29-Mediated Epigenetic Modifications

Previously, we and others have shown that the regular intake of green tea polyphenols (GTPs) reduces ultraviolet B (UVB) radiation-induced skin cancer by targeting multiple signaling pathways, including DNA damage, DNA repair, immunosuppression, and inflammation. Here, we determine the effect of GTPs on UVB-induced epigenetic changes, emphasizing DNA hypermethylation in UV-exposed skin and tumors and their association with miR-29, a key regulator of DNA methyltransferases (DNMTs). Skin cancer was induced in SKH-1 hairless mice following repeated exposures of UVB radiation (180 mJ/cm2, three times/week, 24 weeks) with or without GTPs supplementation (0.2%) in drinking water. Regular intake of GTPs inhibited tumor growth by hindering the cascade of DNA hypermethylation events. GTPs supplementation significantly blocked UVB-induced DNA hypermethylation in the skin (up to 35%; p < 0.0001) and in tumors (up to 50%; p < 0.0001). Experimental results showed that the levels of DNA hypermethylation were higher in GTPs-treated mice than in the control group. The expressions of miR-29a, miR-29b, and miR-29c were markedly decreased in UV-induced skin tumors, and GTPs administration blocked UVB-induced miR-29s depletion. Furthermore, these observations were verified using the in vitro approach in human skin cancer cells (A431) followed by treatment with GTPs or mimics of miR-29c. Increased levels of miR-29 were observed in GTPs-treated A431 cells, resulting in increased TET activity and decreased DNA hypermethylation. In conclusion, UVB-mediated miR-29 depletion promotes DNA hypermethylation and leads to enhanced tumor growth by silencing tumor suppressors. Regular intake of GTPs rescued UVB-induced miR-29 depletion and prevented tumor growth by maintaining reduced DNA hypermethylation and activating tumor suppressors. Our observations suggest that miR-based strategies and regular consumption of GTPs could minimize the risk of UVB-induced skin cancers and contribute to better management of NMSCs.

The non-fatal burden of cancer in Belgium, 2004–2019: a nationwide registry-based study

Background The importance of assessing and monitoring the health status of a population has grown in the last decades. Consistent and high quality data on the morbidity and mortality impact of a disease represent the key element for this assessment. Being increasingly used in global and national burden of diseases (BoD) studies, the Disability-Adjusted Life Year (DALY) is an indicator that combines healthy life years lost due to living with disease (Years Lived with Disability; YLD) and due to dying prematurely (Years of Life Lost; YLL). As a step towards a comprehensive national burden of disease study, this study aims to estimate the non-fatal burden of cancer in Belgium using national data. Methods We estimated the Belgian cancer burden from 2004 to 2019 in terms of YLD, using national population-based cancer registry data and international disease models. We developed a microsimulation model to translate incidence- into prevalence-based estimates, and used expert elicitation to integrate the long-term impact of increased disability due to surgical treatment. Results The age-standardized non-fatal burden of cancer increased from 2004 to 2019 by 6 and 3% respectively for incidence- and prevalence-based YLDs. In 2019, in Belgium, breast cancer had the highest morbidity impact among women, followed by colorectal and non-melanoma skin cancer. Among men, prostate cancer had the highest morbidity impact, followed by colorectal and non-melanoma skin cancer. Between 2004 and 2019, non-melanoma skin cancer significantly increased for both sexes in terms of age-standardized incidence-based YLD per 100,000, from 49 to 111 for men and from 15 to 44 for women. Important decreases were seen for colorectal cancer for both sexes in terms of age-standardized incidence-based YLD per 100,000, from 105 to 84 for men and from 66 to 58 for women. Conclusions Breast and prostate cancers represent the greatest proportion of cancer morbidity, while for both sexes the morbidity burden of skin cancer has shown an important increase from 2004 onwards. Integrating the current study in the Belgian national burden of disease study will allow monitoring of the burden of cancer over time, highlighting new trends and assessing the impact of public health policies.

Moderators of the Effects of mySmartSkin, a Web-Based Intervention to Promote Skin Self-examination and Sun Protection Among Individuals Diagnosed With Melanoma

Background Identifying the characteristics of persons who benefit more from behavioral interventions can help health care providers decide which individuals should be offered particular interventions because this is the subgroup of persons who are more likely to derive greater benefit from the intervention and refine the underlying constructs of the model guiding the intervention. Purpose This study evaluated possible demographic, medical, knowledge and attitudinal, and psychosocial variables that may moderate the impact of an online intervention, called mySmartSkin (MSS), on engagement in skin self-examination (SSE) and sun protection behaviors among melanoma survivors. Methods Participants completed a baseline survey and were then randomized to the MSS condition or usual care. Follow-up surveys were completed by participants at 8-, 24-, and 48-week postrandomization. Results A greater impact of MSS on SSE was illustrated among participants with more phenotypic skin cancer risk factors and participants reporting lower baseline self-efficacy in conducting SSE. A more favorable response of MSS on sun protection behaviors was shown when initial knowledge about abnormal lesions and sun protection barriers were high. Greater use of MSS and more favorable evaluations of it were also associated with higher intervention response. Conclusions Future studies seeking to improve SSE and sun protection among melanoma survivors might benefit from focusing on survivors who report more skin cancer risk factors, lower self-efficacy in conducting SSE, less knowledge about what abnormal skin lesions look like, more perceived barriers to sun protection behaviors, and less worry about recurrence and cancer-related distress.

The skin we live in: pigmentation traits and tanning behaviour in British young adults, an observational and genetically-informed study.

Background: Skin cancer incidence has been increasing worldwide, representing a particularly high burden for populations of European ancestry. Outdoor and indoor tanning using ultraviolet radiation (UVR) devices are major risk factors for skin cancer. While tanning behaviours can be modified by targeted interventions to reduce skin cancer rates, there is insufficient evidence on the motivations for tanning preferences and their relationship with pigmentation phenotypes. The present observational and genetically-informed study investigates motives for tanning and the role that pigmentation phenotypes play on outdoor and indoor tanning behaviour in British young adults. Methods: This study included 3722 participants from the Avon Longitudinal Study of Parents and Children in South West England. Skin, hair and eye colour features, and tanning ability and preferences were collected using a questionnaire applied when participants were ~25 years of age. Genotypes for 41 single nucleotide polymorphisms (SNPs) associated with pigmentation were obtained from a subset of participants who provided a biological sample, and used to estimate the probability of having particular pigmentation traits with the HIrisPlex-S system. Results: Liking to tan and outdoor tanning were strongly influenced by skin, hair and eye pigmentation, and tanning ability. However, the association of these traits with UV indoor tanning was weaker. Conversely, females, participants of lower socioeconomic position, individuals who were unhappy with their pigmentation phenotype during adolescence, and participants who believed that tanning helps prevent sunburn were more likely to have used UVR-based tanning devices. Conclusion: Our results provide evidence to support the implementation of skin cancer preventative interventions that consider individual biological characteristics and motives for undergoing outdoor and indoor tanning.

Immunotherapy in skin cancers - A narrative review

Immunotherapy, in the context of cancers, involves the use of various drugs to stimulate the immune system to target cancer cells. Immunotherapy is being increasingly used for cutaneous malignancies, especially melanoma. Immunity plays an important part in protection against cancer. One of the factors limiting the effectiveness of host immunity is improper recognition of cancer cells. Sometimes, despite recognizing the cancer cells as abnormal, the immune response, for various reasons might not be strong enough to deal effectively with the cancer cells. Immunotherapy basically tries to address the two points mentioned above by improving the capacity of the immune system to recognize and effectively destroy cancer cells. In skin cancers, immunotherapy is best established for melanomas, but is increasingly being used for non-melanoma skin cancers too. This article reviews some of the general concepts about immunotherapy in cancer and discusses in detail, the available options and future possibilities in the applications of immunotherapy in skin cancer.