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Background: MDM2 (Murine Double Minute2) is an oncoprotein that inhibits the P53 activity. Overexpression of MDM2 gene has been reported in several human tumors. In the present study, we aimed to evaluate the impact of 40-bp insertion/deletion (ins/del) polymorphism on the promoter of MDM2 and susceptibility to breast cancer in a sample of Iranian population. Methods: This case-control study was carried out on 236 patients with breast cancer and 203 healthy individuals. Genomic DNA was extracted from the whole blood by the salting-out method. The 40-bp ins/del polymorphism was determined by using polymerase chain reaction. Results: The findings indicated that MDM2 ins/del variant increased the risk of breast cancer in co-dominant- (odds ratio [OR] = 2.09, 95% CI = 1.14-3.85, P = 0.018, del/del vs. ins/ins), dominant- (OR = 1.49, 95% CI = 1.02-2.18, P = 0.038, ins/del + del/del vs. ins/ins), and recessive- (OR = 1.86, 95% CI = 1.03-3.34, P = 0.038, del/del vs. ins/ins + ins/del) tested inheritance models. The del allele increased the risk of breast cancer (OR= 1.48, 95% CI=1.11-1.98, P=0.008) compared with ins allele. Conclusions: Our result revealed that 40-bp ins/del polymorphism in the promoter of MDM2 increased the risk of breast cancer in an Iranian population. Further investigations with larger sample sizes and diverse ethnicities are needed to verify our findings.

Keywords: Breast cancer, Murine Double Minute2 (MDM2), Polymorphism

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