Lung cancer is the epitome of an environmentally induced disease. Eighty-seven percent of lung cancers are attributed to tobacco exposure. However, only a fraction of smokers develop neoplastic lesions. Genetically determined modulation of environmental exposures is an attractive possible mechanism for the variation in host susceptibility. In vitro chromosomal analyses have been frequently used to study individual sensitivity to genotoxicity and cancer risk. Screening of peripheral blood lymphocytes (PBLs) for cytogenetic defects has proven useful in studying other cancers. Deletion of chromosome 9p has been reported in numerous tumor types, especially lung cancer. We have shown that spontaneous chromosome aberrations on chromosome 9 in PBLs were a significant risk predictor for lung cancer. This proposal is designed to build upon those preliminary data and within the recently funded lung-cancer SPORE study which involves collaboration among investigators in basic, clinical, and public-health sciences at The University of Texas Southwestern medical Center and M.D. Anderson Cancer Center. The ongoing study is integrating epidemiologic data with molecular susceptibility factors in patients with newly diagnosed lung cancer to determine the extent of host factors that predispose to lung cancer risk.
The specific aims of this proposed supplementary study are: 1. To determine the relationship between family history of lung cancer and spontaneous chromosome aberrations in PBLs of 00 lung cancer patients with (cases) and 100 without a family history of lung cancer (controls). Our working hypothesis is that spontaneous chromosome aberrations reflect genetic instability and that individuals with such aberrations are more likely to report a family history of cancer than individuals without such aberrations. Chromosome 9 aberrations may be a marker of cancer susceptibility and may be associated with familial aggregation of cancer. 2. To access the associations between the genetic marker and age, cigarette smoking status, and nutrition status by integrating epidemiologic data with the cytogenetic, molecular cytogenetic, and molecular genetic data. Our hypothesis is that spontaneous chromosome 9 aberrations in PBLs are inherited genetic defects that are not associated with specific exposures. These data are being routinely collected in SPORE Project 2. The long-term goal of this study is to further our understanding of lung carcinogenesis. Chromosome 9 aberrations may be useful as biomarkers to identify high-risk populations. Because it builds on an existing study of lung cancer, this proposal is both time and cost effective.
| Zhu, Yong; Spitz, Margaret R; Strom, Sara et al. (2002) A case-control analysis of lymphocytic chromosome 9 aberrations in lung cancer. Int J Cancer 102:536-40 |
