Project 3: Variation in Hormone and Xenobiotic Metabolizing Enzyme Genes and Breast Cancer
In this project, we are testing whether sequence variation in genes involved in the metabolism of sex hormones (e.g., estrogen and androgens) and xenobiotics (e.g., environmental toxins and anticancer drugs) increases the risk of breast cancer. To accomplish this, we have extended existing studies to determine whether sequence variation in specific clusters of genes and enzymes influence breast cancer risk. Constructing genetic profiles for use in risk assessment may increase understanding of the role of gene environment interactions in breast cancer etiology and treatment. Moreover, by researching the role of these genes and enzymes in the metabolism of anticancer agents, the information obtained through these studies may help in dissecting the genetic basis of individual variability in response to cancer treatment and, ultimately, lead to individualized therapy. This would lead to reduced breast cancer morbidity and mortality and improved clinical outcomes for all women with breast cancer. Currently, our specific aims are to:
Aim 1: Re-sequence the UGT2B gene cluster based on comparative genomics analyses in ethnically diverse population samples to select specific pieces of DNA for an association study.
Aim 2: Examine whether variations in the UGT2B genes are associated with breast cancer risk in women of African descent.
Aim 3: Examine whether UGT2B genes and environmental factors are associated with age at diagnosis, tumor grade, and estrogen receptor/progesterone receptor staining.