Scott Winkel defends Master's Technical Report on 8/5/05

Myeloperoxidase (MPO) is an enzyme located within azurophilic granules of neutrophils and lysosomes of monocytes. Its primary function is to assist the innate immune system by acting as a microbicidal agent. MPO activity may be associated with risk of breast cancer due to its ability to produce reactive oxygen species, and metabolize certain xenobiotic compounds. We analyzed DNA samples and exposure information from African-American and white cases and controls in the Carolina Breast Cancer Study to determine whether the /G/ -463 /A/ polymorphism in the promoter region of the MPO gene was associated with increased risk of breast cancer. Next, we evaluated whether MPO -463 genotype modified the effects of exposure to the organochlorines hexachlorobenzene (HCB) and trans-nonachlor. Finally, we looked at interaction between genotypes for MPO and glutathione-S-transferase theta 1 (GSTT1) on breast cancer risk. No association was observed between the MPO (-463) genotype and breast cancer in African American women (Odds Ratio (OR) =1.00; 95% Confidence Interval (CI), 0.80-1.24). Among white women, there was an increased risk for breast cancer in those with the homozygous /A/ allele genotype (OR=1.59; 95% CI, 1.09-2.32). A positive association for the highest lipid-adjusted trans-nonachlor levels was observed among women with the any MPO (-463) /A/ genotype (OR=1.76; 95% CI, 1.07-2.88). ORs for any /A/ allele MPO genotype and a null GSTT1 genotype indicate an increased risk for breast cancer (OR=1.76; 95% CI, 1.04-2.55; referent group = GSTT1 present and homozygous MPO /G/ allele). These findings suggest that the MPO -463/A/ polymorphism may influence breast cancer risk by modifying the effects of environmental exposures through specific metabolic pathways.

Research Adviser: Dr. Bob Millikan

Academic Adviser: Dr. Louise Ball

Committee Member: Dr. Temitope Keku

For further information please contact Rebecca Riggsbee Lloyd by email at Rebecca_Lloyd@unc.edu