Involvement of microRNA-423 Gene Variability in Breast Cancer Progression in Saudi Arabia.

Aim: microRNA-423 is an oncogenic factor which is frequently upregulated in cancer. However, associations with breast cancer risk remain inconsistent. Therefore, we investigated the prevalence of microRNA-423 rs6505162C>T gene variation with breast cancer susceptibility in Saudi women. Methodology: This study was conducted on 100 breast cancer patients and 124 matched healthy individuals. Genotyping of the microRNA-423 rs6505162C/T gene variation was performed by using the amplification refractory mutation system PCR method (ARMS-PCR). Results: A significant difference was observed in the genotype distribution between the breast cancer cases and controls (p=0.0001), the frequencies of the genotypes CC,CT and TT being 25%, 52% and 23% in patients and 65%,20% and 15% respectively, in controls. The microRNA-423 C>T variant was associated with an increased risk of breast cancer in codominant models for (OR = 6.73, 95 % CI, 3.50-12.97; RR 2.35(1.67-3.30, p=0.0001) the microRNA-423TT genotype and (OR = 4.14, 95 % CI, 1.93-8.87; p=0.0003) microRNA-423CT (OR= 6.73, 95% CI, 3.50-12.97; p=0.0001) and also with the dominant model (OR 5.6(3.14-1.01), p=0.0001) CT+TT vs CC) with a non-significant association for the recessive model (OR=1.75, 95%CI=0.08-3.44, P=0.139, TT vs CC+CT). The T allele significantly increased the risk of breast cancer (OR =2.63, 95 % CI, 1.77-3.91; p=0.001) compared to the C allele. Some 6.73 ,4.14 and 2.63 fold increased risk of developing breast cancer was associated with TT and CT genotypes and the T allele of microRNA-423 in the northwestern region of Saudi Arabia. Conclusion: Our findings indicate that the microRNA-423 TT genotype and the T allele are associated with an increased susceptibility, metastasis and advanced stage of breast cancer in Saudi Arabian patients. Further studies with larger sample sizes are necessary to confirm our findings.