Date of Award


Document Type

Campus Access Dissertation


Biological Sciences

First Advisor

Bert Ely


Background: Breast cancer is a heterogeneous disease with no single specific cause and is the second most frequent type of cancer in women in the US. Five percent of breast cancer is caused by mutations in highly penetrant genes such as BRCA1, BRCA2, and p53. The causes of the remaining 95% are still unknown. We hypothesize that germline mutations can affect the risk for specific types of breast cancer.

Methods: RFLP and sequencing were used to assay 17 polymorphic loci in 629 breast cancer patients from South Carolina recruited between the years 2004-2008. Loci were selected based on studies in the literature suggesting that these loci might be associated with breast cancer or with aggressive cancer. Regression analyses were used to examine the relationships between alleles and patient and breast cancer characteristics. To facilitate identifying statistically significance associations in the context of multiple tests, patients were divided into a test group and a validation group based upon date of recruitment, and then randomized to generate a second test and validation group.

Results: Statistically significant associations between several loci and various breast cancer or patient characteristics were identified. After Bonferroni correction for multiple tests, only one locus-parameter association remained significant: the ERα Pos-397 polymorphism was negatively associated with estrogen receptor positive expression status (OR= 0.33, p-value = 0.001).

Conclusions: Comparisons of significant parameter-locus relationships between the two groups of patients were effective at identifying locus-parameters that might be associated with breast cancer subtypes. The ERα-397 locus was statistically associated with estrogen receptor status in our breast cancer patient population.