Marsha Frazier, Ph.D.
Present Title & Affiliation
Professor, Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX
- Genetic risk modifiers for pancreatic cancer
- Genetic predisposition to colorectal cancer (CRC)
- Modifier genes
My laboratory studies genetic factors involved in the pathogenesis of colorectal cancer (CRC). Patients with Lynch syndrome have germline mutations in mismatch repair genes which predispose a person to a variety of different cancers, with CRC being the most common. There is substantial variation in age at onset of cancer and tumor spectrum among Lynch syndrome patients. We are studying the role of additional genetic factors of this disease, such as single nucleotide polymorphisms (SNPs), which may be involved in this variation.
A second genetic disorder we are studying is Peutz-Jeghers syndrome (PJS) which is caused by mutations in the LKB1 gene, and is characterized by the development of intestinal hamartomatous polyps in association with mucocutaneous melanocytic macules. Patients with PJS have a 15-fold increased risk of developing intestinal cancer compared with that of the general population. They are also at increased risk for cancers at other sites as well. We have developed a mouse model for this syndrome and are examining new approaches to prevent the polyps that occur in these mice. This could lead to preventive approaches in humans with PJS.
Another area of research is the elucidation of genetic risk modifiers (SNPs) associated with the risk for development of pancreatic ductal adenocarcinoma (PDAC). Identifying individuals more likely to develop PDAC early will help to identify individuals who would benefit from surveillance. We are using a multigenic pathways-based approach, which assesses the combined effects of a comprehensive panel of SNPs that interact in pathways that are altered in PDAC. This may amplify the effects of individual SNPs and enhance the predictive power. The overall hypothesis of our study is that multiple SNPs in genes within pathways work together to influence age at onset of pancreatic carcinogenesis.
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