News and Events BMDCR
Huggins Lecture Series
Saturdays, January 14 through March 4, 2006
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Most breast cancers occur sporadically (or randomly within a population), but 5-10% of breast cancers occur in clusters within families. These cases are usually caused by inherited mutations in one of two tumor suppressor genes, either BRCA1 or BRCA2. Inherited mutations in these genes are among the strongest predictors of breast cancer occurrence, so patients with strong family histories of breast cancer are often advised to seek genetic screening for BRCA1 or BRCA2 mutations.
The BRCA1 and BRCA2 proteins encoded by these genes are important for repairing damaged DNA and many other functions, but much is still unknown about how they affect breast and ovarian cancer risk. For example: 1) Why do mutations in BRCA1 or BRCA2 result in cancers of the breast and ovary, but few (if any) other tissues? 2) Do the BRCA1 or BRCA2 genes participate in sporadic breast cancers, even when they are not inherited in a mutated state? 3) What are the other genes or environmental conditions that influence the BRCA1 and BRCA2 gene functions? Addressing these and other questions may help clinicians determine who is at greatest risk for breast cancer, and how different individuals may respond to different prevention and treatment strategies.
We examine the naturally occurring variations (or changes in the DNA structure) in the BRCA1 and BRCA2 genes in breast cancer patients and healthy control individuals from Nigeria. Some of these variations are mutations associated with increased breast and ovarian cancer risk. Other variations are “polymorphisms,” or genetic changes that have no impact on gene function. Still other DNA changes are described as “unclassified variants,” and it is not known whether these variants affect gene function or not. We use these variants to address several questions: 1) Are different parts of the BRCA1 and BRCA2 genes required for different functions of the BRCA1 and BRCA2 proteins? 2) Are there variations in the BRCA1 and BRCA2 genes that increase cancer risk in some groups of patients but not others? 3) Are there genetic variations in the BRCA1 or BRCA2 genes that inactivate gene in ways we cannot predict with current screening technologies?
Individuals from Nigeria have a greater diversity of BRCA1 and BRCA2 gene variants than most other populations, and may provide the most data for teasing apart their numerous functions. This diversity may also contribute to the poor breast cancer outcomes in patients of African descent. We characterize the variant groups (haplotypes) that may be associated with breast cancer risk by determining their frequencies in patient and control populations. We also examine the messenger RNA (mRNA) copied from the BRCA1 and BRCA2 gene DNA to identify mutations that might not be detected by DNA sequencing alone. We have already identified a recurring BRCA1 mutation that lies within a haplotype of likely African Ancestry. These studies are being incorporated into a multi-disciplinary information network that may provide better tools for predicting cancer risk, enhancing early-detection screening, and providing individualized treatments for cancer patients.
| Overview and introduction to cancer | January 14, 2006 |
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| Early experiments in genetics: the science of heredity | January 21, 2006 |
| Later experiments in genetics: the science of molecular biology | January 28, 2006 |
| The DNA double helix: structural basis of heredity and molecular biology | February 4, 2006 |
| Gene mutations and cancer, part 1: oncogenes and tumor suppressor genes regulate tumor development | February 11, 2006 |
| Gene mutations and cancer, part 2: hormone action in normal cells and breast tumors | February 18 , 2006 |
| Genetic studies point the way to better treatments | February 25, 2006 |
| From Genetics to Genomics | March 4 , 2006 |