Breast cancer (BC) is one of the most causes of death in women worldwide. It affects Iranian female population approximately a decade earlier than those in other parts of the world. Previous studies have shown that vascular endothelial growth factor (VEGF) gene variants were associated with BC risk. The current study aimed to evaluate the impact of VEGF rs3025039 (+936C>T), rs2010963 (+405C>G), rs833061 (-460T>C), rs699947 (-2578C>A), and rs35569394 (18-bp I/D) polymorphisms on BC risk in an Iranian population in southeast of Iran. This case–control study was done on 250 BC patients and 215 healthy women. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or PCR was used to genotype the polymorphisms. Our findings showed that VEGF rs699947 variant increased the risk of BC (OR = 1.71, 95% CI = 1.15–2.54, P = 0.009, CA vs CC; OR = 2.12, 95% CI = 1.14–3.93, P = 0.021, AA vs CC; OR = 1.78, 95% CI = 1.22–2.60, P = 0.004, CA+AA vs CC; OR = 1.47, 95% CI = 1.12–1.92, P = 0.005, A vs C). The VEGF rs3025039, rs2010963, rs833061, and rs35569394 variants were not associated with risk/protection of BC. In conclusion, our results proposed that VEGF rs699947 polymorphism may increase the risk of BC development. Furthers studies with larger sample sizes and different ethnicities are necessary to confirm our findings.
Aim: MicroRNAs (miRNAs) are small noncoding RNAs that function as oncogene or tumor suppressors. The single nucleotide polymorphisms in miRNAs potentially can alter miRNA-binding sites on target genes as well as affecting miRNAs expression. The present study aimed to evaluate the impact of miR-608 rs4919510 C>G variant on breast cancer (BC) risk. Materials and Me thods: This case-control study conducted on 160 women with BC and 192 age-matched healthy women. Genotyping of miR608 rs4919510 was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: Our findings showed that GC genotype significantly decreased the risk of BC (odds ratio (OR) = 0.49, 95% confidence interval (CI) 0.28–0.88, p = 0.018) compared to CC genotype. Furthermore the G allele decreased the risk of BC (OR = 0.53, 95%CI 0.30–0.92, p = 0.024). No significant association was found between miR-609 genotypes and clinicopathological characteristics of BC patients (p > 0.05). Conclusion: Our findings indicate that miR-608 polymorphism might be associated with decreased risk of BC in an Iranian subpopulation. Further large-scale studies with different ethnicities are needed to verify our findings.
Abstract. MicroRNAs (miRNAs or miRs) are a family of small non-coding RNAs that function as oncogenes or tumor suppressor genes. Recent evidence suggests that the pri-miR-34b/c rs4938723 variant is associated with the development of cancer. At present, there is an inconsistent association between the single-nucleotide polymorphism in pri-miR-34b/c and cancer in the limited studies. The present study is a case-control investigation, with 263 breast cancer (BC) patients and 221 control women, which examined the potential association of the pri-miR-34b/c rs4938723 polymorphisms with BC susceptibility. The polymorphisms were genotyped by the polymerase chain reaction restriction fragment length polymorphism method. No significant association between the pri-miR-34b/c rs4938723 variant and BC was identified [TC vs. TT: Odds ratio (OR), 0.87; 95% confidence interval (CI), 0.60-1.26; P=0.506; CC vs. TT: OR, 1.22; 95% CI, 0.61-2.47; P= 0.600; TC+CC vs. TT: OR, 0.91; 95% CI, 0.64-1.31; P= 0.648; CC vs. TT+TC: OR, 1.32; 95% CI, 0.67-2.59; P= 0.498; C vs. T: OR, 0.99; 95% CI, 0.75-1.31; P= 0.986]. However, a significant association was observed between the pri-miR-34b/c rs4938723 genotypes and clinicopathological characteristics, such a grade, progesterone receptor and human epidermal growth factor receptor 2 status were observed (P<0.05). These findings suggest that the pri-miR-34b/c rs4938723 variant may not be a risk factor for the development of BC. IntroductionBreast cancer (BC), the most prevalent type of cancer in women, is a major public and global health problem and accounts for 14% of total annual cancer fatalities worldwide (1). Similarly, BC is the most common malignancy affecting Iranian women (2). Although the etiology of BC remains to be identified, genetic factors are shown to have important roles in the pathogenesis and progress of this malignancy (3-8).MicroRNAs (miRNAs or miRs) are a class of single-stranded non-coding RNA typically 17-25 nucleotides in length that have key roles in the regulation of cellular processes by targeting mRNAs for cleavage or translational repression (9,10). They regulate the expression of genes at the post-transcriptional level by targeting the 3' untranslated regions of mRNAs. Cumulative evidence suggests that the dysregulation of miRNA expression is involved in the tumorigenesis by acting as tumor suppressors or oncogenes (11-15). Single-nucleotide polymorphisms (SNPs) or mutations in miRNA genes can affect the miRNA biosynthesis and expression of target genes, therefore resulting in diverse functional consequences and thereby possibly representing potentially important biomarkers for the prognosis of cancer (7,(16)(17)(18).The pri-miR-34b/c gene resides in a CpG island within the intron of the B-cell translocation gene 4. Therefore, it is expected that pri-miR-34b/c is co-transcribed by either the promoter of the protein-coding gene or by its own transcription initiation region, as is the case with the majority of miRNAs, whether they are intergenic or located within the i...
Abstract. Flap endonuclease 1 (FEN1), a DNA repair protein, is important in preventing carcinogenesis. Two functional germ line variants -69G>A (rs174538) and +4150G>T (rs4246215) in the FEN1 gene have been associated with risk of various types of cancer. The aim of the present study was to evaluate the possible impact of FEN1 polymorphisms on risk of breast cancer (BC) in a sample of Iranian subjects. The FEN1 -69G>A and +4150G>T polymorphisms were analyzed in a case-control study that included 266 BC patients and 225 healthy females. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to genotype the variants. The findings demonstrated that the FEN1 -69G>A and +4150G>T polymorphisms were not associated with BC risk in co-dominant, dominant and recessive inheritance models. The findings indicated that GG/GT, GA/GG and GA/TT genotypes significantly decreased the risk of BC when compared with -69GG/+4150GG. Furthermore, haplotype analysis indicated that -69G/+4150T as well as -69A/+4150G significantly decreased the risk of BC compared with -69G/+4150G. Thus, these findings demonstrated that haplotypes of FEN1 -69G>A and +4150G>T polymorphisms decreased the risk of BC in an Iranian population. Further studies with larger sample sizes and different ethnicities are required to validate the present findings.
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