Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES049017-07
Application #
6672960
Study Section
Epidemiology and Biometry Training Committee (EB)
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2002
Total Cost
Indirect Cost

  Institution

Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Carpenter, Catherine L; Yu, Mimi C; London, Stephanie J (2009) Dietary isothiocyanates, glutathione S-transferase M1 (GSTM1), and lung cancer risk in African Americans and Caucasians from Los Angeles County, California. Nutr Cancer 61:492-9
Lee, Won Jin; Brennan, Paul; Boffetta, Paolo et al. (2002) Microsomal epoxide hydrolase polymorphisms and lung cancer risk: a quantitative review. Biomarkers 7:230-41
Benhamou, Simone; Lee, Won Jin; Alexandrie, Anna-Karin et al. (2002) Meta- and pooled analyses of the effects of glutathione S-transferase M1 polymorphisms and smoking on lung cancer risk. Carcinogenesis 23:1343-50
London, Stephanie J; Yuan, Jian-Min; Travlos, Gregory S et al. (2002) Insulin-like growth factor I, IGF-binding protein 3, and lung cancer risk in a prospective study of men in China. J Natl Cancer Inst 94:749-54
David-Beabes, G L; London, S J (2001) Genetic polymorphism of XRCC1 and lung cancer risk among African-Americans and Caucasians. Lung Cancer 34:333-9
Stern, M C; Umbach, D M; Yu, M C et al. (2001) Hepatitis B, aflatoxin B(1), and p53 codon 249 mutation in hepatocellular carcinomas from Guangxi, People's Republic of China, and a meta-analysis of existing studies. Cancer Epidemiol Biomarkers Prev 10:617-25
Garte, S; Gaspari, L; Alexandrie, A K et al. (2001) Metabolic gene polymorphism frequencies in control populations. Cancer Epidemiol Biomarkers Prev 10:1239-48
Devereux, T R; Stern, M C; Flake, G P et al. (2001) CTNNB1 mutations and beta-catenin protein accumulation in human hepatocellular carcinomas associated with high exposure to aflatoxin B1. Mol Carcinog 31:68-73
David-Beabes, G L; Lunn, R M; London, S J (2001) No association between the XPD (Lys751G1n) polymorphism or the XRCC3 (Thr241Met) polymorphism and lung cancer risk. Cancer Epidemiol Biomarkers Prev 10:911-2
Stucker, I; Boffetta, P; Antilla, S et al. (2001) Lack of interaction between asbestos exposure and glutathione S-transferase M1 and T1 genotypes in lung carcinogenesis. Cancer Epidemiol Biomarkers Prev 10:1253-8

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