Retraction Note to: Epigenetich Mechanisms Involved in the Etiology of Lung Cancers: From Noncoding RNAs to Exosomal Noncoding RNAs.

Objectives: Genetic susceptibility also has significant effects on the etiology of lung cancer, besides smoking. Previously it has been reported that some genetic polymorphisms have important roles; especially Glutatyon S-Transferaz P1 (GSTP1) gene for the development of lung cancer. GSTP1 gene has a role in phase II of xenobiotic metabolism. GSTP1 Exon-6 polymorphisms have functional effects on gene production and causes differences in enzyme activity.The aim of this study was to investigate probable effects of GSTP1gene exon-6 (ala114val) polimorphism on the etiology of lung cancer. Materials and methods: Our research population consistsed of 160 subjects; 80 as control group and 80 suffering from lung cancer. Genomic DNA was extracted from peripheral blood leukocytes and the genotypes have been determined by using PCR and RFLP methods. Results: No effect of exon 6 (ala114val) polymorphism genotype of GSTP1 gene were found on etiology of lung cancer in present study. This study showed that smoking, old age and being male are important risk factors for lung cancer. Additionally, our sample\'s GSTP1 gene exon 6 (ala114val) polymorphism genotype frequencies were determined. Conclusions: Our data derived from present study did not suggest an effect of GSTP1gene exon-6 (ala114val) polimorphism on the etiology of lung cancer.

Lung cancer is associated with one of the highest cancer-related mortality rates and is the second most prevalent cancer worldwide. Diagnosis and treatment of lung cancer has different challenges as in most cases, and it is often diagnosed late when metastatic spread is widely disseminated. The development of chemo- and radioresistance of lung cancer, as well as a lack of specific treatment, has resulted in a very high mortality and morbidity. Noncoding RNAs (ncRNAs) are a group of RNAs with a wide spectrum of functions required for homeostasis. These RNAs modulate the expression of proteins posttranslationally and control the cell phenotype. Studies have shown that these RNAs could act as both oncogene and oncosuppressor, and due to their great therapeutic and diagnostic potential, recent studies have also focused on their use as biomarkers for early detection of cancers. Understanding the current findings in this field would help scientists to have an overview about different ncRNAs and their role in lung cancer progression. This chapter explores the landscape of ncRNA research related to lung cancer, highlighting the potential for novel diagnostic and therapeutic strategies.

The etiology of lung cancer in never-smokers remains elusive, despite 15% of lung cancer cases in men and 53% in women worldwide being unrelated to smoking. Here, we aimed to enhance our understanding of lung cancer pathogenesis among never-smokers using untargeted metabolomics. This nested case-control study included 395 never-smoking women who developed lung cancer and 395 matched never-smoking cancer-free women from the prospective Shanghai Women's Health Study with 15,353 metabolic features quantified in pre-diagnostic plasma using liquid chromatography high-resolution mass spectrometry. Recognizing that metabolites often correlate and seldom act independently in biological processes, we utilized a weighted correlation network analysis to agnostically construct 28 network modules of correlated metabolites. Using conditional logistic regression models, we assessed the associations for both metabolic network modules and individual metabolic features with lung cancer, accounting for multiple testing using a false discovery rate (FDR) < 0.20. We identified a network module of 121 features inversely associated with all lung cancer (p = .001, FDR = 0.028) and lung adenocarcinoma (p = .002, FDR = 0.056), where lyso-glycerophospholipids played a key role driving these associations. Another module of 440 features was inversely associated with lung adenocarcinoma (p = .014, FDR = 0.196). Individual metabolites within these network modules were enriched in biological pathways linked to oxidative stress, and energy metabolism. These pathways have been implicated in previous metabolomics studies involving populations exposed to known lung cancer risk factors such as traffic-related air pollution and polycyclic aromatic hydrocarbons. Our results suggest that untargeted plasma metabolomics could provide novel insights into the etiology and risk factors of lung cancer among never-smokers.

Lung cancer is a dominant cause of cancer mortality. The etiology of lung cancer is mainly related to cigarette smoking, airborne genotoxic carcinogens, and arsenic, but its sex-specific incidence suggests that other mechanisms, such as hormones, may also be involved in the process of carcinogenesis. A number of agents commonly present in the living environment can have dual biological effects: not only are they genotoxic / carcinogenic, but they are also hormonally active as xenoestrogens. This dualism may explain sex-specific differences reported in both types and incidence of lung cancer. In a novel approach to investigate the complexity of lung cancer, etiology, including systems biology, will be used as a tool for a simultaneous interpretation of measurable environmental and biological parameters. Using this approach, the etiology of human lung cancer can be more thoroughly investigated using the available data from oncology and environmental health. The information gained could be applied in the introduction of preventive measures, in personalized medicine, and in more relevant legislation, which should be adjusted to reflect the current knowledge on the complex environmental interactions underlying this life-threatening disease.

Lung cancer is the leading cause of cancer death among women in the United States and other Western nations. The predominant cause of lung cancer in women is active cigarette smoking. Secondhand exposure to tobacco smoke is another important cause. The hypothesis that women are more susceptible than men to smoking-induced lung cancer has not been supported by the preponderance of current data, as noted by De Matteis et al. (Am J Epidemiol. 2013;177(7):601-612) in the accompanying article. However, aspects of lung cancer in men and women continue to indicate potential male-female differences in the etiology of lung cancer, based on several observations: 1) among never smokers, women have higher lung cancer incidence rates than men; 2) there is evidence that estrogen may contribute to lung cancer risk and progression; and 3) there are different clinical characteristics of lung cancer in women compared with men, such as the higher percentage of adenocarcinomas in never smokers, the greater prevalence of epidermal growth factor receptor gene (EGFR) mutations in adenocarcinomas among never smokers, and better prognosis. Considered in total, observations such as these offer enticing clues that, even amid cigarette smoking and other commonalities in the etiology of lung cancer in men and women, distinct differences may remain to be delineated that could potentially be of scientific and clinical relevance.

P2.10-01 Analysis of Human Papilloma Viruses (HPV) and Human Polyoma Viruses (HPyV) in Lung Cancer from Swedish Never-Smokers

Background: The etiology of lung cancer among never-smokers is unclear despite 15% of cases in men and 53% in women worldwide are not smoking-related. Metabolomics provides a snapshot of dynamic biochemical activities, including those found to be driving tumor formation and progression. This study used untargeted metabolomics with network analysis to agnostically identify network modules and independent metabolites in pre-diagnostic blood samples among never-smokers to further understand the pathogenesis of lung cancer. Methods: Within the prospective Shanghai Women’s Health Study, we conducted a nested case-control study of 395 never-smoking incident lung cancer cases and 395 never-smoking controls matched on age. We performed liquid chromatography high-resolution mass spectrometry to quantify 20,348 unique metabolic features in plasma. Because metabolic features are expected to be highly correlated and more likely to be involved in biological processes as a network of intertwined features than individually, we agnostically constructed 28 network modules using a weighted correlation network analysis approach. The associations between metabolite network modules and individual metabolites with lung cancer were assessed using conditional logistic regression models, adjusting for age, body mass index, and exposure to environmental tobacco smoke. We accounted for multiple testing using a false discovery rate (FDR) &amp;lt; 0.20. Results: We identified a network module of 122 metabolic features enriched in lysophosphatidylethanolamines that was associated with all lung cancer combined (p = 0.001, FDR = 0.028) and lung adenocarcinoma (p = 0.002, FDR = 0.056) and another network module of 440 metabolic features that was associated with lung adenocarcinoma (p = 0.014, FDR = 0.196). Metabolic features were enriched in pathways associated with cell growth and proliferation, including oxidative stress, bile acid biosynthesis, and metabolism of nucleic acids, carbohydrates, and amino acids, including 1-carbon compounds. Conclusions: Our prospective study suggests that untargeted plasma metabolomics in pre-diagnostic samples could provide new insights into the etiology of lung cancer in never-smokers. Replication and further characterization of these associations are warranted. Citation Format: Mohammad L. Rahman, Xiao-Ou Shu, Douglas Walker, Dean P. Jones, Wei Hu, Bu-tian Ji, Batel Blechter, Jason YY Wong, Qiuyin Cai, Gong Yang, Tu-Tang Gao, Wei Zheng, Nathaniel Rothman, Qing Lan. A nested case-control study of untargeted plasma metabolomics and lung cancer risk among never-smoking women in the prospective Shanghai Women’s Health Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6056.

Exosomal non-coding RNAs have a significant effect on tumor metastasis

To determine the role of meat consumption and related mutagens in the etiology of lung cancer, we conducted a case-control study among Uruguayan males in the time period 1996-2004. The study included 846 cases and 846 controls, frequency matched on age and residence. Both series were drawn from the four major public hospitals in Montevideo, Uruguay. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) of lung cancer by quartiles of meat intake and mutagens. The highest vs. the lowest quartile of intake of total meat (OR = 2.04, 95% CI 1.42-2.92), red meat (OR = 2.33, 95% CI 1.63-3.32), and processed meat (OR = 1.79, 95% CI 1.22-2.65) was associated with increased risk of lung cancer, while intake of total white meat, poultry and fish was not. Heterocyclic amines (IQ, MeIQx, PhIP), nitrosamines and benzo[a]pyrene were directly associated with the risk of lung cancer (OR for PhIP 2.16, 95% CI 1.48-3.15). Moreover, both red meat and meat mutagens displayed higher risks among former smokers compared with current smokers. This study suggests that red and processed meat and meat mutagens may play a role in the etiology of lung cancer.

CA: A Cancer Journal for CliniciansVolume 4, Issue 2 p. 49-53 ArticleFree Access The place of tobacco in the etiology of lung cancer E. Cuyler Hammond Sc.D., E. Cuyler Hammond Sc.D.Search for more papers by this author E. Cuyler Hammond Sc.D., E. Cuyler Hammond Sc.D.Search for more papers by this author First published: March 1954 https://doi.org/10.3322/canjclin.4.2.49Citations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume4, Issue2March 1954Pages 49-53 ReferencesRelatedInformation

Colorectal cancer (CRC) accounts for 9.7% of all cancers which makes it one of the three most commonly diagnosed cancer types worldwide. Prognosis of the patients with CRC depends mainly on the extent of the disease at the time of diagnosis. Therefore, the early detection of CRC and precancerous lesions is one of the main requirements of successful treatment. In recent years exosomes emerged as potential reservoirs of clinically useful biomarkers. Exosomes are 30-150 nm sized membranous vesicles that are endogenously produced by almost all cell types. They participate in intercellular communication by delivering proteins, microRNAs (miRNAs), mRNAs or long non-coding RNAs (lncRNAs) to recipient cells. In the context of cancer, intercellular communication allows cancer cells to create a favorable microenvironment for their growth. It has been shown that cancer-derived exosomes promote pathways contributing to hallmarks of cancer.To investigate diagnostic potential of exosomal RNA in CRC, blood serum samples were collected from patients with CRC and age- and sex-matched controls. Exosome isolation protocol was optimized, and the presence of vesicles in the exosome size range was confirmed using both dynamic light scattering (DLS) analysis as well as electron microscopy (TEM). Downstream analysis of serum exosomal RNA using next-generation sequencing (Illumina NextSeq 550) from exploratory cohort of CRC samples (N=50) and healthy controls (N=20) revealed both coding and non-coding RNAs to be differentially expressed (FC&amp;gt;1.5, p-value &amp;lt; 0.01). Among these were genes already reported to be dysregulated in CRC such as GAS5, but also lncRNAs previously unreported in CRC exosomes (AC103760.1, LINC02709 or PGBP) were identified. Gene set enrichment analysis (GSEA) was used to link RNAs identified within exosomes to their molecular functions. Using the Hallmark gene sets (MsigDB) as a reference, we discovered high enrichment of genes related to MYC targets, E2F targets and G2M checkpoint in healthy controls compared to CRC samples. All three hallmarks comprise genes crucial for cell proliferation. The first results indicated that the exosomal RNAs could be promising candidates as new diagnostic biomarkers in CRC, although further in vitro and in vivo exploration of identified differentially expressed lncRNAs is necessary. This work was supported by Ministry of Health of the Czech Republic grant nr. NU20-03-00127, NV19-03-00501 and NV19-03-00559. All rights reserved. Citation Format: Tina Catela Ivkovic, Marie Mądrzyk, Karolina Trachtova, Petra Faltejskova-Vychytilova, Tana Machackova, Petra Pokorna, Jaroslav Juracek, Jiri Sana, Ondrej Slaby. Molecular and functional characterization of colorectal cancer derived-exosomes and exosomal coding and long non-coding RNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2802.

ObjectivesGenetic susceptibility in work-related lung cancer aetiology could have an important public health impact. Few studies have previously evaluated this issue, with inconsistent results. We aimed to investigate interactions between...

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