Background and objectives: Breast cancer is the leading cause of death in women. Cytokines regulate the intensity and continuity of immune response by balancing cell-mediated immunity and humoral responses. This study aimed to investigate the relationship between two polymorphisms of the interleukin-16 (IL-16) gene and risk of breast cancer. Methods: Blood samples were collected from 80 breast cancer patients and 80 healthy individuals. Polymorphisms rs11556218 T/G and rs4072111 C/T were investigated by polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR). Then, genotype and allele frequency distributions were evaluated in each group using the SPSS software (version 24). Results: The frequency of genotype rs11556218 differed significantly between the patients and controls (P=0.007). The TG genotype (odds ratio [OR]= 2.471, 95% confidence intervals [CI]: 1.229-4.965, P= 0.001) and total TG+GG genotypes (OR= 3.095, 95% CI: 1.624-5.899, P= 0.001) had a significant relationship with increased risk for breast cancer. The allele and genotype frequencies of rs4072111 C/T polymorphism did not differ significantly between the patients and controls. Conclusion: Our findings suggest that the rs11556218 T/G polymorphism of the IL- 16 gene may be associated with susceptibility to breast cancer
