This project includes three studies. The first is a case-control study of genetic polymorphisms and lung cancer risk among African-Americans and Caucasians in Los Angeles. The second is a nested case-control study within a cohort study of 18,000 men in Shanghai, China. In the past year, we have examined polymorphisms in DNA repair genes in the Los Angeles study. These genes are XRCC1, XPD, and XRCC3. In the Shanghai cohort, we have examined the relation between insulin-like growth factor-1 (IGF-1) and its major binding protein, IGFBP-3, in relation to lung cancer risk using the prospectively collected samples. There are few prospective data on IGF-1 and lung cancer risk. In the past year, we found an interaction between a biomarker for dietary intake of isothiocyanates and glutathione S-transferase polymorphisms in relation to lung cancer risk in the Shanghai cohort. We are following up this observation in the Los Angeles samples. The third study is a collaborative pooling effort with other studies of lung cancer and genetic polymorphisms, the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens. In this study, we have the power to investigate gene-environment and gene-gene interactions that cannot be examined in the individual studies. We found that subjects with higher levels of IGFBP-3 were at reduced risk of lung cancer using the prospectively collected samples from the Shanghai cohort. Because the disease process, or its effects, may alter levels of IGF-1 and IGFBP-3, this association must be addressed in prospectively collected samples. This result adds to the literature because there is only one other prospective study of lung cancer and IGF-1 and ours is considerably larger. In the past year, we have published two papers on polymorphisms in DNA repair genes and lung cancer risk. We found that two polymorphisms in the XRCC1 gene may contribute to lung cancer risk in an interactive manner with amount smoked. We did not find an association with polymorphisms in the XPD and XRCC3 genes and have published this result as well.
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