Dissertation Defense: Joy Adigun
Candidate Name: Joy Adigun
Major: Biochemistry and Molecular Biology
Thesis Advisor: MaryBeth Martin, Ph.D.
Title: Associations between Polymorphisms in Genes in the Nitrite Synthesis Pathway and Mammographic Breast Density, a Biomarker of Breast Cancer Risk
The nitrite synthesis pathway can play a role in breast cancer by activating the estrogen receptor alpha (ERα), in the absence of estradiol, through an interaction with the ligand binding domain of the receptor. ERα plays significant roles in breast tissue proliferation and development, and thus mammographic breast density (MBD). As MBD is an established risk factor for breast cancer and an intermediate biomarker of breast cancer risk, we investigated the association between polymorphisms in twenty-three genes in the nitrite synthesis pathway and elevated MBD. This was done to enable a better understanding the role of this pathway in breast cancer etiology and its role in breast cancer risk.
We investigated associations between mean percent breast density (PBD), as proxy for MBD, and 530 single nucleotide polymorphisms (SNPs) in two SNP genotype studies of 1400 adult women enrolled in a cross-sectional study between 2005 and 2019. The study centers were MedStar Georgetown University Hospital and the Georgetown University’s Capital Breast Care Center, both in Washington, D.C. We measured breast density using the user assisted Cumulus software from the University of Toronto. SNP genotype data were generated using Illumina’s Inc.’s GoldenGate® Genotyping Assay with Veracode technologyTM on the BeadXpress reader, and Illumina’s global screening array version 3 plus (GSAv3+) on the iScan system.
We observed allele-specific associations in a total of twenty SNPs across nine genes in the nitrite synthesis pathway. We also observed significant differences in mean PBD values in study participants with a combination of alleles identified to be associated with mean PBD, compared to participants with few or none of the identified alleles. Our findings support the novel hypothesis that the nitrite synthesis pathway may play a role in breast cancer etiology. Our results highlight the impact on elevated breast density values in participants with several of the identified SNPs that are associated with mean PBD, thus providing an improvement to the understanding of how MBD serves as a risk factor for breast cancer. Our results underscore the need to further investigate the role of signaling pathways in breast cancer risk.