Molecular Epidemiology

The laboratory is interested in understanding how gene-environment interactions affect individual susceptibility to diseases such as cancer and asthma. These studies are concerned with questions of how specific genetic polymorphisms might predict the environmental etiology of a disease or its clinical outcome. For example, one project involved understanding how specific polymorphisms in Cytochrome P450 genes affect a woman’s risk of breast cancer if she is exposed to environmental chemicals such as tobacco smoke, alcohol or PCBs, polychlorinated biphenyls (1). Another project examined how polymorphisms in the metabolic pathways of oxidative agents such as free radicals affect a person risk of hearing loss when exposed to noise (2). A third project looked at how polymorphisms in the glutathione-S-transferase genes (GSTM1 and GSTT1) affect an individual's response to chemotherapy.

Figure 1. Genotyping GSTM1 and GSTT1

Figure 1 shows the method for determining GSTM1 and GSTT1 genotypes. CYP1A1 is included as an amplification control. Lane 21 is a molecular weight marker. Lane 21 is included as a negative control. Lanes 2-3, 5-20, 22 and 23 are GSTT1 present. Lanes 4 and 23 are GSTT1 null. Lanes 4, 6-7, and 10 are GSTM1 present. Lanes 2-3, 5, 8-9, 11-20, 22-24 are GSTM1 null. Samples are from a case-control study in progress on the relationship of PCB exposure, GST genotype and breast cancer.

References

1. Zhang, Y, Wise, Sr., J.P., Holford, T.R., Xie, H., Boyle, P., Zahm, S.H., Zou, K.Y., Zhang B., Owens, P.H., Zheng, T. Serum Polychlorinated Biphenyls, Cytochrome P4501A1 Polymorphisms, and Risk of Breast Cancer in Connecticut Women. American Journal of Epidemiology 160(12):1177-1183, 2004.
2. Rabinowitz, P.M., Wise, Sr., J.P., Antonucci, P.G., Mobo, B.H. Glutathione-S-Transferase Polymorphism and High Frequency Otoacoustic Emissions in Noise-Exposed Workers. Hearing Research 173: 164-171, 2002.