scholarly journals The Role of DNA Methylation in the Development and Progression of Lung Adenocarcinoma

2007 ◽  
Vol 23 (1-2) ◽  
pp. 5-30 ◽  
Author(s):  
Keith M. Kerr ◽  
Janice S. Galler ◽  
Jeffrey A. Hagen ◽  
Peter W. Laird ◽  
Ite A. Laird-Offringa
Keyword(s):  
United States ◽  
Lung Cancer ◽  
Dna Methylation ◽  
Lung Adenocarcinoma ◽  
Western Europe ◽  
Cpg Islands ◽  
The United States ◽  
Smoke Inhalation ◽  
Genetic Changes ◽  
Never Smokers

Lung cancer, caused by smoking in ∼87% of cases, is the leading cause of cancer death in the United States and Western Europe. Adenocarcinoma is now the most common type of lung cancer in men and women in the United States, and the histological subtype most frequently seen in never-smokers and former smokers. The increasing frequency of adenocarcinoma, which occurs more peripherally in the lung, is thought to be at least partially related to modifications in cigarette manufacturing that have led to a change in the depth of smoke inhalation. The rising incidence of lung adenocarcinoma and its lethal nature underline the importance of understanding the development and progression of this disease. Alterations in DNA methylation are recognized as key epigenetic changes in cancer, contributing to chromosomal instability through global hypomethylation, and aberrant gene expression through alterations in the methylation levels at promoter CpG islands. The identification of sequential changes in DNA methylation during progression and metastasis of lung adenocarcinoma, and the elucidation of their interplay with genetic changes, will broaden our molecular understanding of this disease, providing insights that may be applicable to the development of targeted drugs, as well as powerful markers for early detection and patient classification.

scholarly journals Lung Cancer Mortality Among Smokers and Never-Smokers in the United States

Epidemiology ◽  
2020 ◽  
Vol 31 (3) ◽  
pp. e24-e25
Author(s):  
H. Dean Hosgood ◽  
Candace Cosgrove ◽  
Madelyn Klugman ◽  
Thomas Rohan ◽  
Sean Altekruse
Keyword(s):  
United States ◽  
Lung Cancer ◽  
Cancer Mortality ◽  
Lung Cancer Mortality ◽  
The United States ◽  
Never Smokers

scholarly journals Lung Adenocarcinoma Biomarker Incidence in Hispanic Versus Non-Hispanic White Patients

2013 ◽  
Vol 138 (3) ◽  
pp. 390-394 ◽  
Author(s):  
Elizabeth McQuitty ◽  
Wei Zhang ◽  
Heather Hendrickson ◽  
Fermin O. Tio ◽  
Jaishree Jagirdar ◽  
...  
Keyword(s):  
United States ◽  
Lung Adenocarcinoma ◽  
The United States ◽  
Smoking History ◽  
Genetic Changes ◽  
Mutational Frequency ◽  
Hispanic Patients ◽  
Biomarker Testing ◽  
Hispanic White ◽  
White Patients

Context.—Lung cancer is the leading cause of cancer deaths in the United States and worldwide. Biomarker testing is critical to personalized therapy in lung adenocarcinoma and has been extensively investigated in non-Hispanic whites, Asians, and African Americans. However, little information addresses the underlying genetic changes in lung adenocarcinoma among Hispanic patients in the United States. Objective.—To identify targetable biomarkers other than EGFR and EML4-ALK in Hispanic patients with lung adenocarcinoma. Design.—We tested DNA extracted from 85 lung adenocarcinoma specimens collected from 40 Hispanic and 43 non-Hispanic white patients for previously reported mutations in KRAS, MET, BRAF, mTOR, STAT3, JAK2, PIK3CA, AKT1 through AKT3, and PTEN with a custom Sequenom massARRAY assay (Sequenom, San Diego, California). Results.—Mutations in KRAS were identified in 11 cases (13%; 6 Hispanic [7%], 5 non-Hispanic white [6%]) and had no correlation with sex, age, or smoking history. Mutations in PIK3CA were identified in 2 of the 40 Hispanic patients (5%), including one patient (2.5%) with a concurrent KRAS mutation. The tumors were wild type for all other genes tested. Conclusions.—Targetable biomarkers other than EGFR and EML4-ALK were identified in 7 of the 40 Hispanic patients (18%) and 5 of the 43 non-Hispanic white patients (12%), suggesting a similar mutational frequency. Our highly multiplexed genotyping assay detected actionable mutations in 14% (12 of 83) more patients than would have been identified by EGFR and EML4-ALK testing alone.

scholarly journals Cost-effectiveness and health impact of lung cancer screening with low-dose computed tomography for never smokers in Japan and the United States: a modelling study

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Akiko Kowada
Keyword(s):  
United States ◽  
Lung Cancer ◽  
Cost Effectiveness ◽  
Lung Cancer Screening ◽  
Cost Effective ◽  
The United States ◽  
Sensitivity Analyses ◽  
Life Years ◽  
Never Smokers ◽  
Low Dose Computed Tomography

Abstract Background Never smokers in Asia have a higher incidence of lung cancer than in Europe and North America. We aimed to assess the cost-effectiveness of lung cancer screening with low-dose computed tomography (LDCT) for never smokers in Japan and the United States. Methods We developed a state-transition model for three strategies: LDCT, chest X-ray (CXR), and no screening, using a healthcare payer perspective over a lifetime horizon. Sensitivity analyses were also performed. Main outcomes were costs, quality-adjusted life-years (QALYs), life expectancy life-years (LYs), incremental cost-effectiveness ratios (ICERs), and deaths from lung cancer. The willingness-to-pay level was US$100,000 per QALY gained. Results LDCT yielded the greatest benefits with the lowest cost in Japan, but the ICERs of LDCT compared with CXR were US$3,001,304 per QALY gained for American men and US$2,097,969 per QALY gained for American women. Cost-effectiveness was sensitive to the incidence of lung cancer. Probabilistic sensitivity analyses demonstrated that LDCT was cost-effective 99.3–99.7% for Japanese, no screening was cost-effective 77.7% for American men, and CXR was cost-effective 93.2% for American women. Compared with CXR, LDCT has the cumulative lifetime potential for 60-year-old Japanese to save US$117 billion, increase 2,339,349 QALYs and 3,020,102 LYs, and reduce 224,749 deaths, and the potential for 60-year-old Americans to cost US$120 billion, increase 48,651 QALYs and 67,988 LYs, and reduce 2,309 deaths. Conclusions This modelling study suggests that LDCT screening for never smokers has the greatest benefits and cost savings in Japan, but is not cost-effective in the United States. Assessing the risk of lung cancer in never smokers is important for introducing population-based LDCT screening.

Lung Cancer in Never Smokers: A Review

2007 ◽  
Vol 25 (5) ◽  
pp. 561-570 ◽  
Author(s):  
Janakiraman Subramanian ◽  
Ramaswamy Govindan
Keyword(s):  
United States ◽  
Lung Cancer ◽  
Growth Factor Receptor ◽  
The United States ◽  
Management Options ◽  
Relative Significance ◽  
Histologic Subtype ◽  
Molecular Abnormalities ◽  
Tk Inhibitors ◽  
Never Smokers

Lung cancer is the leading cause of cancer-related death in the United States. Although tobacco smoking accounts for the majority of lung cancer, approximately 10% of patients with lung cancer in the United States are lifelong never smokers. Lung cancer in the never smokers (LCINS) affects women disproportionately more often than men. Only limited data are available on the etiopathogenesis, molecular abnormalities, and prognosis of LCINS. Several etiologic factors have been proposed for the development of LCINS, including exposure to radon, cooking fumes, asbestos, heavy metals, and environmental tobacco smoke, human papillomavirus infection, and inherited genetic susceptibility. However, the relative significance of these individual factors among different ethnic populations in the development of LCINS has not been well-characterized. Adenocarcinoma is the predominant histologic subtype reported with LCINS. Striking differences in response rates and outcomes are seen when patients with advanced non–small-cell lung cancer (NSCLC) who are lifelong never smokers are treated with epidermal growth factor receptor tyrosine kinase (EGFR-TK) inhibitors such as gefitinib or erlotinib compared with the outcomes with these agents in patients with tobacco-associated lung cancer. Interestingly, the activating mutations in the EGFR-TK inhibitors have been reported significantly more frequently in LCINS than in patients with tobacco-related NSCLC. This review will summarize available data on the epidemiology, risk factors, molecular genetics, management options, and outcomes of LCINS.

Anne O. Krueger, Constantine Michalopoulos and Vernon W. Ruttan. Aid and Development. Baltimore: The Johns Hopkins University Press. 1989. xiv + 386 pp.Price: U.S. $ 52.00

1991 ◽  
Vol 30 (2) ◽  
pp. 213-217
Author(s):  
Mir Annice Mahmood
Keyword(s):  
United States ◽  
Economic Development ◽  
International Development ◽  
Western Europe ◽  
Development Assistance ◽  
The United States ◽  
Social Infrastructure ◽  
Low Literacy ◽  
The Subject ◽  
The Impact

Foreign aid has been the subject of much examination and research ever since it entered the economic armamentarium approximately 45 years ago. This was the time when the Second World War had successfully ended for the Allies in the defeat of Germany and Japan. However, a new enemy, the Soviet Union, had materialized at the end of the conflict. To counter the threat from the East, the United States undertook the implementation of the Marshal Plan, which was extremely successful in rebuilding and revitalizing a shattered Western Europe. Aid had made its impact. The book under review is by three well-known economists and is the outcome of a study sponsored by the Department of State and the United States Agency for International Development. The major objective of this study was to evaluate the impact of assistance, i.e., aid, on economic development. This evaluation however, was to be based on the existing literature on the subject. The book has five major parts: Part One deals with development thought and development assistance; Part Two looks at the relationship between donors and recipients; Part Three evaluates the use of aid by sector; Part Four presents country case-studies; and Part Five synthesizes the lessons from development assistance. Part One of the book is very informative in that it summarises very concisely the theoretical underpinnings of the aid process. In the beginning, aid was thought to be the answer to underdevelopment which could be achieved by a transfer of capital from the rich to the poor. This approach, however, did not succeed as it was simplistic. Capital transfers were not sufficient in themselves to bring about development, as research in this area came to reveal. The development process is a complicated one, with inputs from all sectors of the economy. Thus, it came to be recognized that factors such as low literacy rates, poor health facilities, and lack of social infrastructure are also responsible for economic backwardness. Part One of the book, therefore, sums up appropriately the various trends in development thought. This is important because the book deals primarily with the issue of the effectiveness of aid as a catalyst to further economic development.

The tyrosine kinase TEK is differentially expressed in non-small cell lung adenocarcinomas.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
United States ◽  
Tyrosine Kinase ◽  
Lung Adenocarcinoma ◽  
Microarray Data ◽  
The United States ◽  
Small Cell ◽  
Small Cell Lung ◽  
Significant Differential Expression ◽  
Lung Cancers ◽  
Lung Adenocarcinomas

Non-small cell lung adenocarcinoma (NSCLC) is a leading cause of death in the United States and worldwide (1, 2). We mined published microarray data (3, 4, 5) to discover genes associated with NSCLC. We identified significant differential expression of the tyrosine kinase TEK in tumors from patients with NSCLC. TEK may be of relevance to the initiation, progression or maintenance of non-small cell lung cancers.

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