Association of Genetic Risk Variants in SETBP1, FANCM, and LSP1 with Familial Breast Cancer in the Pakistani Pashtun Population

Background and Objective: Familial breast cancer is often linked to inherited gene mutations. These mutations significantly increase the risk of developing breast cancer within affected families. The objective of this study was to identify genetic risk variants in SETBP1, FANCM, and LSP1 genes and its association with familial breast cancer in Pakistani Pashtun population. Methodology: This case-control study was conducted at the Genomic Center, Rehman Medical Institute, Peshawar, from January 10/2018 to February 01/2020. A total of n=172 individuals were included in the study, consisting of 86 breast cancer subjects (cases) and 86 Healthy participants (controls). Whole exome sequencing and follow-up association analysis was used to identify risk variants associated with breast cancer. Results: Exome sequencing identified four variants in genes of our interest (SETBP1, FANCM, and LSP1). Among these, the SNP rs11082414 in SETBP1 (crude P=0.011; adjusted p=0.003) showed a strong positive association with breast cancer in the Pakistani Pashtun population. Whereas SNPs rs34252356 in FANCM (crude P=0.260; adjusted p=0.199), rs793842 in LSP1 (crude P=0.220; adjusted p=0.173), and rs621679 in SETBP1 (crude P=0.112; adjusted p=0.207) showed no notable association with breast cancer in the study population. Conclusion: This research enhances our understanding of the genetic risk factors for breast cancer in the Pashtun population and underscores the potential importance of the SETBP1 rs11082414 variant in identifying individuals at risk. The identification of genetic biomarkers can facilitate the development of targeted drug therapies, improve early detection, and enhance the effective management of breast cancer.