Author(s): Emma Richardson
Mentor(s): Holli Loomans-Kropp
Institution BYU
Colorectal cancer (CRC) is projected to be the third most diagnosed cancer in 2024 and one of the top four causes of cancer-related deaths. Prior research has shown that individuals with type 2 diabetes mellitus (T2DM) have an increased risk of CRC. Metformin is the most prescribed drug used to treat T2DM and has been associated with reduced CRC risk. Despite the suspected cancer preventive efficacy of metformin, some individuals who take metformin continue to develop CRC. Furthermore, the pathway through which metformin works to prevent CRC remains unknown. The objective of the current study is to investigate the differences in gene expression, and ultimately key pathways, of CRC patients who used metformin, compared to non-users. This case-control study utilized genomic and clinical data collected as part of the Oncology Research Information Exchange Network (ORIEN) and The Ohio State University Total Cancer Care Protocol. Cases had a diagnosis of T2DM and a history of metformin use. Controls had a diagnosis of T2DM and no history of metformin use. The RNA of participant tumors was sequenced, and Galaxy was used for sequencing analysis. An adjusted p-value <.05 served as the reference for statistical significance. SAS was utilized for statistical analysis of clinical data. We identified 27 eligible participants, 15 without T2DM, 6 metformin users with T2DM and 6 non-metformin users with T2DM. Only participants with T2DM were used for gene expression analysis. Approximately 92% of the study was white, with 58% being male and 42% being female. The average age of metformin users was 67.5 years, and the average age of non-metformin users was 62.0 years. Principle component analysis of RNA sequencing data showed no distinct clustering between analysis groups (PC1:30%, PC2:22%). Compared to non-users, the MUC5AC gene was found to have decreased expression in T2DM participants using metformin with a log fold change of -9.42 (p-value = 1.30*10-8). Future work should validate these findings in vitro on CRC cells and through a large prospective study of known metformin users and non-users.