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BMC Medicine (1)
Bondy, Melissa L. (1)
Brothers, John F (1)
El-Zein, Randa A (1)
Hijazi, Kahkeshan (1)
Mascaux, Celine (1)
Spira, Avrum (1)
Spitz, Margaret R (1)
Spitz, Margaret R. (1)
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Bridging the clinical gaps: genetic, epigenetic and transcriptomic biomarkers for the early detection of lung cancer in the post-National Lung Screening Trial era
Brothers, John F
El-Zein, Randa A
Lung cancer is the leading cause of cancer death worldwide in part due to our inability to identify which smokers are at highest risk and the lack of effective tools to detect the disease at its earliest and potentially curable stage. Recent results from the National Lung Screening Trial have shown that annual screening of high-risk smokers with low-dose helical computed tomography of the chest can reduce lung cancer mortality. However, molecular biomarkers are needed to identify which current and former smokers would benefit most from annual computed tomography scan screening in order to reduce the costs and morbidity associated with this procedure. Additionally, there is an urgent clinical need to develop biomarkers that can distinguish benign from malignant lesions found on computed tomography of the chest given its very high false positive rate. This review highlights recent genetic, transcriptomic and epigenomic biomarkers that are emerging as tools for the early detection of lung cancer both in the diagnostic and screening setting.
Biomarker; Diagnostics; Early detection; Epigenetics; Genetics; Lung cancer; Screening; Transcriptomics
The evolving discipline of molecular epidemiology of cancer
Bondy, Melissa L.
Classical epidemiologic studies have made seminal contributions to identifying the etiology of most common cancers. Molecular epidemiology was conceived of as an extension of traditional epidemiology to incorporate biomarkers with questionnaire data to further our understanding of the mechanisms of carcinogenesis. Early molecular epidemiologic studies employed functional assays. These studies were hampered by the need for sequential and/or prediagnostic samples, viable lymphocytes and the uncertainty of how well these functional data (derived from surrogate lymphocytic tissue) reflected events in the target tissue. The completion of the Human Genome Project and Hapmap Project, together with the unparalleled advances in high-throughput genotyping revolutionized the practice of molecular epidemiology. Early studies had been constrained by existing technology to use the hypothesis-driven candidate gene approach, with disappointing results. Pathway analysis addressed some of the concerns, although the study of interacting and overlapping gene networks remained a challenge. Whole-genome scanning approaches were designed as agnostic studies using a dense set of markers to capture much of the common genome variation to study germ-line genetic variation as risk factors for common complex diseases. It should be possible to exploit the wealth of these data for pharmacogenetic studies to realize the promise of personalized therapy. Going forward, the temptation for epidemiologists to be lured by high-tech ‘omics’ will be immense. Systems Epidemiology, the observational prototype of systems biology, is an extension of classical epidemiology to include powerful new platforms such as the transcriptome, proteome and metabolome. However, there will always be the need for impeccably designed and well-powered epidemiologic studies with rigorous quality control of data, specimen acquisition and statistical analysis.
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