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Abstract Over the past years, our understanding of the pathogenesis of lung cancer has advanced impressively. Environmental carcinogens and a gene locus determining susceptibility have been identified. The pathology of lung cancer has been classified into categories with major clinical implications.
The cellular and molecular genetic changes underlying lung cancer have become better understood over the past 25 years, but the stepwise progression of respiratory epithelium from normal to neoplastic is not yet well demarcated, limiting abilities to advance early detection and chemoprevention.
The translation of improved understanding of dominant signal transduction pathways in lung cancer to rationally designed therapeutic strategies has had recent successes, demonstrating a proof of principle for targeted therapy in lung cancer.
Improvement in overall patient outcomes has been stubbornly slow and will require concerted efforts. Etiology A century ago, one occupational cause of lung cancer was known.
An association between lung cancer and work in the Schneeberg mines in Germany was described by Harting and Hesse in 2. Subsequently, high levels of radon gas were found in the mines and an etiologic connection between radioactive gas exposure and lung carcinogenesis was proposed early in the twentieth century.
Tobacco was used for centuries before the modern epidemic of lung cancer occurred. However, with the development of machines for the commercial production of cigarettes in the late nineteenth century, tobacco products became more widely and intensively used.
Tobacco smoke was suspected as causing lung cancer as early as the late s, when physicians began seeing increasing numbers of patients with this heretofore rare disease and noted that nearly all were cigarette smokers.
Muller reported a case-control study implicating tobacco smoke in causing lung cancer in Germany inbut the message was largely lost as the Pathophysiology of lung cancer community was distracted by the larger disaster of World War II, as reviewed by Muller and by Witschi 34.
Inseveral case-control studies were published, all showing an association between cigarette smoking and lung cancer 56.
A number of studies have demonstrated that risk for lung cancer decreases with smoking cessation, most recently and elegantly described in the Lung Health Study, where the efficacy of smoking cessation interventions in decreasing lung cancer deaths was demonstrated in a prospective, controlled trial 7.
Inthe German scientific consensus was that asbestos exposure caused lung cancer. Experiments performed by the asbestos industry showed that asbestos exposure caused lung tumors in mice, but were unpublished 8.
InDoll published a landmark manuscript demonstrating a highly persuasive association between heavy asbestos exposure and lung cancer 9. Similar to tobacco, there was a long delay between the documentation of the etiologic effect of asbestos in lung carcinogenesis and implementation of policies to protect the public.
Additional industrial and environmental exposures, including heavy metals and petrochemicals, causing lung cancer have been described. Viral causation of lung cancer has been intermittently considered. Bronchioloalveolar carcinoma in sheep is transmitted by a retrovirus, but no studies in human lung cancer have supported a retroviral etiology There is recent evidence supporting human papilloma viruses as possibly contributing to lung cancer, especially in never-smokers from Pacific Rim countries 11 Different carcinogens give rise to specific mutations i.
Thus, sequence analysis of the mutational spectrum of target genes, such as p53, in different populations can be informative regarding the probable culprit carcinogen in that population.
This approach to determining etiology has been termed molecular epidemiology or molecular archeology and has been instrumental in providing additional support for tobacco smoke as a major etiology of lung cancer 13 — A number of reports suggest increasing numbers of lung cancer cases in never-smokers, particularly females from Asia This is particularly alarming and mandates aggressive investigation, including both standard and molecular epidemiology, to determine if new etiologies for lung cancer are emerging.
Small cell lung cancer SCLC was first described as a tumor of the bronchus, as opposed to a round cell sarcoma, by Barnard in Azzopardi further refined the pathologic description in and Watson and Berg described some of the distinctive clinical features in 18 Although the subtypes of SCLC are not clinically useful in determining therapy, the recognition that mixed tumors containing two or more elements of SCLC, adenocarcinoma, or squamous cell carcinoma has promoted the concept that the major forms of lung cancer are closely related, perhaps arising from a common stem cell.
Genetic Susceptibility Mice develop pulmonary adenomas, either spontaneously or in response to carcinogens, that progress to adenocarcinomas in a strain-dependent fashion This strain difference in susceptibility to lung tumors has been used to map murine pulmonary adenoma susceptibility and resistance genes.
To date, murine lung tumor susceptibility genes have not lead to the identification of similar susceptibility genes in humans. An inherited genetic susceptibility to lung cancer in humans was first suggested in the early s More recently, family history of lung cancer has been confirmed as a strong risk factor for the development of lung cancer Segregation analysis supported the presence of a highly penetrant autosomal gene determining genetic susceptibility to lung cancer This has been a daunting task, due to the difficulties in obtaining DNA from cases, most of whom are deceased.
Ina locus on chromosome 6q23—25 was reported as conferring lung cancer susceptibility among families with multiple members affected by lung or head and neck cancer Of great interest, in carriers even a small exposure to tobacco smoke greatly increases risk for lung cancer.
The identity of this gene is currently a topic of intense research interest.It causes about 90 percent of lung cancer cases. Tobacco smoke contains many chemicals that are known to cause lung cancer. If you still smoke, quitting smoking is the single best thing you can do for your lung .
Lung cancer is one of the most common cancers in the world. It is a leading cause of cancer death in men and women in the United States.
Cigarette smoking causes most lung cancers. Oct 23, · The pathophysiology of lung cancer is a complicated issue. Genes that are influenced in the pathogenesis of lung cancer are proteins that are involved in a variety of processes including cell growth and differentiation, cell cycle processes, and angiogenesis, which is .
Lung cancer includes two main types: non-small cell lung cancer and small cell lung cancer. Smoking causes most lung cancers, but nonsmokers can also develop lung cancer.
Explore the links on this page to learn more about lung cancer treatment, prevention, screening, statistics, research, clinical. The incidence of lung cancer is strongly correlated with cigarette smoking, with about 90% of lung cancers arising as a result of tobacco use.
. Lung cancer is one of the most common cancers in the world. It is a leading cause of cancer death in men and women in the United States. Cigarette smoking causes most .