Effect of variation in miRNA-binding site (rs8176318) of the BRCA1 gene in breast cancer patients

BACKGROUND/AIM: A variation in the 3 prime untranslated regions (3′-UTRs) affects the binding of microRNA (miRNA) to the breast cancer (BC) susceptibility gene 1 (BRCA1) gene, and thus regulate its expression. In this study, the consequences of a variation in the miRNA-binding site (rs8176318G>T) in the 3′-UTRs of BRCA1 and its association with the risk of BC were investigated. MATERIALS AND METHODS: The selected variation (rs8176318G>T) was genotyped in BC patients (n = 300) and healthy controls (n = 300) using allele-specific polymerase chain reaction (PCR) [tetra-primer amplification refractory mutation system-PCR (T-ARMS-PCR)]. The results of the T-ARMS-PCR were further confirmed by Sanger sequencing through a random selection of 10% previously analyzed samples by T-ARMS-PCR. Association of this variation with BC was tested by calculating the odds ratio (OR) (at 95% CI) and χ2-value using 4 different genetic models (codominant, dominant, recessive, and additive models). RESULTS: Using Fisher’s exact test, a significant association between variant rs8176318 (G>T) and BC was found in codominant [χ2-value = 15.68, df: 2 P < 0.0004], dominant [OR = 1.557 (1.082–2.241), P <0.0213], recessive [OR = 0.474 (0.3204–0.7017), P = 0.0002] and additive models [OR = 1.609 (1.282–2.018), P < 0.0001]. CONCLUSION: It was therefore concluded that there is a significant association between rs8176318 and BC risk in a case-control study in a Pakistani population. Furthermore, an association study using a large sample size is required to further verify these findings.