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Breast cancer (BC) is the most frequently diagnosed cancer among women in the world. Genetic polymorphisms in Interleukin (IL) genes are one of the most important risk factors in BC. The aim of this study was to investigate the association of rs1946518 C/A polymorphism in the promoter region of the IL-18 gene and BC risk in Iranian women. In this case-control study, we recruited 140 women with BC as a case group and 140 age and ethnically matched women as healthy controls from East Azerbaijan, Tabriz in Iran. The genomic DNA was extracted using a salting-out method from peripheral blood leukocytes. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The genotype distribution in BC patients was 37.86% CC, 47.14% CA, and 15.00% AA, whereas in healthy controls these were 40.72% CC, 42.85% CA, and 16.43% AA. Statistical analysis showed that the genotype and allele frequencies of IL-18 rs1946518 C/A polymorphism were not significantly different between BC patients and healthy controls (p>0.05). The only significant difference between cases and controls was related to family history (p=0.023). In conclusion, our study indicated that IL-18 rs1946518 C/A polymorphism was not associated with BC in the Iranian women population. However, more studies on different races and geographic areas are required to determine the exact role of rs1946518 C/A polymorphism in prognosis, diagnosis, and risk of BC. [ABSTRACT FROM AUTHOR]