Shift work with circadian disruption has been considered as a carcinogenic risk factor for skin cancer. the few prior studies that investigated the association between shift work and skin cancer have inconclusive results. our main objective was to evaluate the associations between shift work and the risks of different types of skin cancer. We systematically searched PubMed, Web of Science, Cochrane Library, EMBASE and Science Direct until October 2018 for studies that included a relationship between shift work and skin cancer. Our search yielded 193 articles and 9 studies met the criteria for our review. The included studies involved 3,579,147 participants and 17,308 skin cancer cases. Overall, ever shift work, was associated with increased risk of melanoma (RR = 1.10, 95% CI = 1.05-1.16) and a significant decrease in the risk of BCC (RR = 0.90, 95% CI = 0.88-0.93). No association between shift work and the risk of SCC was detected. Interestingly, our dose response analysis demonstrated that the risk of melanoma cumulatively increases by 2% for every year of shift work (RR = 1.02; 95% CI = 1.00-1.03). In conclusion, shift work is associated with increased risk of melanoma and deceased risk of BCC. Further studies are needed to confirm our findings and to elucidate the related potential biological mechanisms. Shift work is increasingly common, especially in industrially developed countries. It includes a wide range of schedules, such as evening work; night work; split, extended or rotating shifts; weekend work; and on-call work 1,2. According to the most recent data from the Bureau of Labour Statistics, approximately 15 million Americans work night shifts, and that number is expected to grow rapidly 3. Although such work imposes significant costs on workers, including many hazardous impacts not only on their relationships, social lives and sleep patterns but also on their overall health, it is unavoidable and is taken for granted by many companies. Indeed, the International Agency for Research in Cancer (IARC) considered shift work that involves circadian disruption to be a probable carcinogenic factor in humans (Group 2 A carcinogen) 4. The desynchronization that occurs in circadian rhythms with respect to sleep cycles and melatonin production predisposes employees to have a higher susceptibility to cardiovascular, neuropsychiatric and endocrine disorders and to the development of neoplastic growths 5. A recent meta-analysis showed that shift work increases the risks of multiple primary cancers, such as breast, prostate and digestive system cancers 6. According to the last annual report by the Skin Cancer Foundation, skin cancer is the most commonly diagnosed cancer in the USA 7. It can be classified into melanoma skin cancer, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The last two subtypes are grouped together as non-melanoma skin cancer which is the most frequently diagnosed cancer in white populations 8. Both BCC and SCC have a good prognosis when detected in their early stages. While most n...

miRNAs, a group of short noncoding RNAs, are key regulators of fundamental cellular processes and signaling pathways. Dysregulation of miRNA expression with known oncogenic or tumor suppressor functions has been associated with neoplastic transformation. Numerous studies have reported dysregulation of miRNA-141, miR-181b1, and miR-23b in a wide range of malignancies, including breast cancer. To the best of our knowledge, no previous study had demonstrated the expression of miR-141-3p, miR-181b1-5p, and miR-23b-3p in different histological grades and molecular subtypes of breast cancer. Here, we identified differential expression of these three miRNAs in breast cancer tissues compared with benign breast fibroadenomas. In addition, high expression levels of miR-141-3p and miR-181b1-5p are strongly associated with aggressive breast carcinomas. We also confirmed the clinical potential of using the three miRNAs individually or combined as diagnostic and prognostic markers in breast cancer. Using bioinformatics analyses, we identified 23 hub genes of these three miRNAs which are involved in key signaling pathways in breast cancer. Furthermore, the KM plotter online database analysis demonstrates the association between elevated expression of miR-141 and miR-181b and shorter overall survival of breast cancer patients. Together, our data suggest an oncogenic role of the studied miRNAs and highlight their molecular roles and potential clinical applications in breast cancer.

Phospholipase A2 receptor 1 (PLA2R1) expression and its role in the initiation and progression of breast cancer are an unresolved issue. PLA2R1 was found to endorse several tumor suppressive responses, including cellular senescence and apoptosis. Previous in vitro studies demonstrated that DNA hypermethylation was highly associated with the epigenetic silencing of PLA2R1 in breast cancer cell lines. Our objective was to study the level of PLA2R1 mRNA expression and the methylation of its promoter in different histological grades and molecular subtypes of breast cancer. We performed bioinformatics analyses on available human breast cancer expression datasets to assess the PLA2R1 mRNA expression. We used qRT-PCR to evaluate the PLA2R1 mRNA expression and its promoter’s methylation in breast cancer tissue in comparison to breast fibroadenomas. Our results describe, for the first time, the expression of PLA2R1 and the methylation of its promoter in human breast cancer tissues. A significant downregulation of PLA2R1, together with hypermethylation of the promoter was detected in breast cancers of different histological grades and molecular subtypes when compared to benign breast tissues. PLA2R1 promoter hypermethylation was associated with aggressive subtypes of breast cancer. In conclusion, PLA2R1 promoter hypermethylation is a potentially useful diagnostic and prognostic biomarker and could serve as a possible therapeutic target in breast cancer.