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Background: Non-smoking-related lung adenocarcinoma (LUAD) has its own characteristics. Genetic and microenvironmental differences in smoking and non-smoking LUAD patients were analyzed to elucidate the oncogenesis of non-smoking-related LUAD, which will improve our understanding of the underlying molecular mechanism and be of clinical use in the future., Methods: The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) databases were used for clinical and genomic information. Various bioinformatics tools were used to analyze differences in somatic mutations, RNA and microRNA (miRNA) expression, immune infiltration, and stemness indices. GO, KEGG, and GSVA analyses were performed with R. A merged protein-protein interaction (PPI) network was constructed and analyzed. A miRNA-differentially expressed gene network was constructed with miRNet. qRT-PCR was used for validation of 4 most significantly differently expressed genes and 2 miRNAs in tumor samples obtained from 20 pairs of non-smoking and smoking patients., Results: Five hundred and one patients with LUAD were obtained, including 210 in the non-smoking group and 292 in the smoking group. A total of 174 significantly altered somatic mutations were detected, including mutations in tumor protein p53 and epidermal growth factor receptor, which were downregulated in non-smoking-related LUAD. At the RNA level, 231 significantly differentially expressed genes were obtained; 124 were upregulated and 107 downregulated in the non-smoking group. GSVA analysis revealed 42 significant pathways. Other functional and enrichment analyses of somatic mutations and RNA expression levels revealed that these genes were significantly enriched in receptor activity regulation and receptor binding. Differences in microenvironments including immune infiltration (e.g., CD8 + T cells and resting mast cells) and stemness indices were also found between groups. A 79-pair interaction was found between differentially expressed genes and miRNAs, of which miR-335-5p and miR-34a-5p were located in the center. Twenty-one genes, including vitronectin, neurotensin, and neuronatin, were differentially expressed in both non-smoking LUAD patients and DMSO-treated A549 cells. And the different expression of neurotensin, neuronatin, trefoil factor family2, regenerating family member 4, miR-377-5p, miR-34a were verified with the same tendency in our own samples., Conclusions: Non-smoking LUAD patients, compared to smokers, have different characteristics in terms of somatic mutation, gene, and miRNA expression and the microenvironment, indicating a diverse mechanism of oncogenesis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-276). The authors have no conflicts of interest to declare., (2020 Translational Lung Cancer Research. All rights reserved.)

A 48-year-old woman with severe pain and numbness of her right leg and foot was admitted to our hospital. She had never smoked and had little exposure to passive smoking. Initially, polyarteritis nodosa with anti-phospholipid antibodies was considered. Combination therapy with methylprednisolone pulse therapy, intravenous cyclophosphamide pulse therapy, vasodilators, antiplatelet agents, and anticoagulants was not effective. Vasculopathy was progressive, and she presented with gangrene of the toes. She required amputation of her right leg. The pathological findings of the amputated leg revealed thromboangiitis obliterans (TAO). TAO should be considered even in non-smoking women. Non-response to immunosuppressant and anticoagulant therapies may be a clue to the diagnosis of TAO.

Background: DNA methylation is associated with cancer, metabolic, neurological, and autoimmune disorders. Hypomethylation of aryl hydrocarbon receptor repressor (AHRR) especially at cg05575921 is associated with smoking and lung cancer. Studies on the association between AHRR methylation at cg05575921 and sources of polycyclic aromatic hydrocarbon (PAH) other than smoking are limited. The aim of our study was to assess the pattern of blood DNA methylation at cg05575921 in non-smoking Taiwanese adults living in areas with different PM2.5 levels. Methods: Data on blood DNA methylation, smoking, and residence were retrieved from the Taiwan Biobank dataset (2008–2015). Current and former smokers, as well as individuals with incomplete information were excluded from the current study. The final analysis included 708 participants (279 men and 429 women) aged 30–70 years. PM2.5 levels have been shown to increase as one moves from the northern through central towards southern Taiwan. Based on this trend, the study areas were categorized into northern, north-central, central, and southern regions. Results: Living in PM2.5 areas was associated with lower methylation levels: compared with the northern area (reference area), living in north-central, central, and southern areas was associated with lower methylation levels at cg05575921. However, only methylation levels in those living in central and southern areas were significant (β= − 0.01003, P = 0.009 and β = − 0.01480, P < 0.001, respectively. Even though methylation levels in those living in the north-central area were not statistically significant, the test for linear trend was significant (P < 0.001). When PM2.5 was included in the regression model, a unit increase in PM2.5 was associated with 0.00115 (P < 0.001) lower cg05575921 methylation levels. Conclusion: Living in PM2.5 areas was inversely associated with blood AHRR methylation levels at cg05575921. The methylation levels were lowest in participants residing in southern followed by central and north-central areas. Moreover, when PM2.5 was included in the regression model, it was inversely associated with methylation levels at cg05575921. Blood methylation at cg05575921 (AHRR) in non-smokers might indicate different exposures to PM2.5 and lung cancer which is a PM2.5-related disease. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of dietary factors on tongue cancer in smoking and non-smoking population., Methods: A case-control study was performed including 251 tongue cancer patients with pathologically confirmed in a hospital in Fuzhou and 1382 healthy community controls from December 2011 to March 2016. Face-to-face interviews were used to collect the information about demographics characteristics, dietary habits, smoking, drinking, etc. Unconditional logistic regression analysis was used to calculate the odds ratios( ORs) and 95% confidence intervals( 95% CI) to examine thedietary factors related to tongue cancer and to assess multiplicative interactions., Results: Intake of fish ≥3 times/week, seafood ≥1 times/week, milk and dairy products ≥1times/week, green vegetables ≥1 times/day, non-green leafy vegetables ≥ 1 times/day and fruits ≥3 times/week were all associated with decreased risk of tongue cancer. When stratified by smoking, the protective effects of fish, seafood, green vegetables and nongreen leafy vegetables on tongue cancer were more obvious in smokers. And the statistically significant association between daily intake of meat ≥3 times/week and tongue cancer was only emerged in smokers( adjusted OR = 1. 55, 95% CI 1. 02- 2. 34). Moreover, there is a positive multiplicative interaction between smoking and meat intake( OR multiplicative = 2. 08, 95% CI1. 43-3. 03)., Conclusion: Moderate intake of fresh fruits and vegetables, fish and seafood, milk and dairy products, and low intake of meat( especially for smokers) may reduce tongue cancer risk to a certain extent.