INHBB variants as genetic determinants of breast density modulate breast cancer risk

Background: One of the most common cancers worldwide is breast cancer (BC), which is influenced by genetics and environmental factors such as mammographic density. Studies suggested INHBB genetic polymorphisms as potential risk factors for breast cancer/density. Therefore, this study was conducted to validate this correlation in a cohort of the Iranian population. Methods: Five ml of peripheral blood was collected from 200 patients and 200 healthy women. Mammographic density was determined by mammograms. rs11902591, rs4328642, and rs10183524 of the INHBB gene were genotyped using the ARMS-PCR method. Haplotype frequencies and statistical analysis were estimated using PHASE and SPSS 16.0 software, respectively. Results: There was no association between rs1192591 and breast density, whereas this polymorphism was associated with breast cancer risk [per allele p = 0.040; OR = 0.56, 95%CI (0.32-0.97)]. Conversely, the C/T genotype of rs4328642 was significantly higher in individuals with dense breasts [p = 0.002; OR = 2.31, 95%CI (1.37-3.89)]. Furthermore, rs10183524 was statistically associated with breast density [p = 0.009; OR = 0.55, 95%CI (0.35-0.86)] and cancer risk [p = 0.031; OR = 0.52, 95%CI (0.29-0.94)]. Also, certain haplotypes and diplotypes of these markers were associated with BC risk and/or breast density. Conclusion: According to the findings, INHBB gene polymorphisms affect cancer risk and density of the breast, and the interaction between alleles in the form of haplotypes and diplotypes may modulate the amount of the risk conferred by these variants.