High polygenic risk score is a risk factor associated with colorectal cancer based on data from the UK Biobank

by Mei Yang, Vagheesh M. Narasimhan, F. Benjamin Zhan

Colorectal cancer (CRC) is a common cancer among both men and women and is one of the leading causes of cancer death worldwide. It is important to identify risk factors that may be used to help reduce morbidity and mortality of the disease. We used a case-control study design to explore the association between CRC, polygenic risk scores (PRS), and other factors. We extracted data about 2,585 CRC cases and 9,362 controls from the UK Biobank, calculated the PRS for these cases and controls based on 140 single nucleotide polymorphisms, and performed logistic regression analyses for the 11,947 cases and controls, for an older group (ages 50+), and for a younger group (younger than 50). Five significant risk factors were identified when all 11,947 cases and controls were considered. These factors were, in descending order of the values of the adjusted odds ratios (aOR), high PRS (aOR: 2.70, CI: 2.27–3.19), male sex (aOR: 1.52, CI: 1.39–1.66), unemployment (aOR: 1.47, CI: 1.17–1.85), family history of CRC (aOR: 1.44, CI: 1.28–1.62), and age (aOR: 1.01, CI: 1.01–1.02). These five risk factors also remained significant in the older group. For the younger group, only high PRS (aOR: 2.87, CI: 1.65–5.00) and family history of CRC (aOR: 1.73, CI: 1.12–2.67) were significant risk factors. These findings indicate that genetic risk for the disease is a significant risk factor for CRC even after adjusting for family history. Additional studies are needed to examine this association using larger samples and different population groups.