) Lung cancer has been the leading cause of death due to malignancy in the United States for decades. While cigarette smoking has been identified as a major risk factor, it is known that only a small proportion of all heavy smokers will develop lung cancer eventually. Evidence of lung cancer familial aggregation suggests variability in inherited susceptibility. Genetic polymorphisms in several microsomal mixed-function oxidases and phase II detoxification enzymes, both of which are important in the activation and detoxification of chemical carcinogens, have been reported to affect risk of lung cancer. Genomic alterations and instabilities have also been indicated for lung cancer risk in the recent literature. In addition, studies of both smokers and nonsmokers suggested overlapping etiology between lung cancer and selected chronic pulmonary diseases. Thoroughly evaluating the intricate roles and interactive effects of major susceptibility gene(s), risk modifier gene(s), and exogenous carcinogens requires a comprehensive study design and data resource which integrates the traditional epidemiologic approaches and newly developed genetic and molecular tools. The purpose of this protocol is to identify newly diagnosed lung cancer patients seen at Mayo Clinic and to build a patient, family and biosample resource for a comprehensive genetic-epidemiologic study of lung cancer. From the estimated 3,840 lung cancer patients newly diagnosed at the clinic between 1/1/1995 and 12/31/1998, 1,118 will be identified as study subjects. There are 250 Olmsted county residents anticipated for population-based studies. Data on approximately 900 selected clinical-based patients will be available for the following genetic and molecular epidemiologic studies: (1) 384 patients with positive family history of lung cancer and 152 patients with strong family history of cancer in general will be ascertained for identifying lung cancer susceptibility gene(s); (2) 190 nonsmoking and 114 young-age (50 years old at diagnosis) patients will be identified for investigating the causes other than or in addition to tobacco smoking; (3) 100 sporadic cases who are smokers older than 50 years will also be included as an internal comparison group. Thus, the developed data resource will enable us to further test and locate the lung cancer susceptibility gene and its interaction with other genes and tobacco exposure. A specific hypothesis, i.e. whether lung cancer is associated with alpha-1 antitrypsin deficiency heterozygous status, will be tested in this proposed study.
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