Abstract
BACKGROUND: Genetic studies play a significant role in understanding the underlying risk factors of breast cancer. Polymorphism in the tumor suppressor gene TP 53, CDH1 and ATM genes are found to increase susceptibility for breast cancer globally. OBJECTIVE: This study aimed to identify/analyze the contribution of genetic polymorphisms in the breast cancer candidate genes ATM, TP53 and CDH1 that may be associated with familial breast cancer risk in the Khyber Pakhtunkhwa population. SUBJECTS AND METHODS: In the present case-control study, Whole Exome Sequencing (WES) of the 100 breast cancer patients and 100 ethnic controls were performed for the selected genes in the target population. RESULTS: Of the studied variants rs3743674 of the CDH1 gene (crude P=0.014 and adjusted p=0.000) evident significant association with breast cancer in Pakistani Pashtun population. Whereas TP53rs1042522 (crude P=0.251 and adjusted P=0.851) and ATM rs659243 (crude p=0.256 and adjusted p=0.975) showed no or negative association with breast cancer in study population. CONCLUSION: The present study demonstrates that CDH1rs3743674 polymorphism is associated with elevated breast cancer risk in the Pashtun ethic population of Khyber Pakhtunkhwa.