Evaluation of prodynorphin gene polymorphisms and their association with heroin addiction in a sample of the southeast Iranian population.

Genetic factors are supposed to account for about 30-50% of the predisposition to cocaine and heroin addiction. This study aims at investigating the effect of rs2281285, rs2235749, rs910080 and 68bp VNTR polymorphisms of prodynorphin (PDYN) gene on heroin dependence risk in a sample of the southeast Iranian population. This case-control study was done on 216 heroin dependence subjects and 219 healthy subjects. Genomic DNA was extracted from peripheral blood cells using salting out method. Genotyping of PDYN polymorphisms were performed using polymerase chain reaction (PCR) or PCR-RFLP method. The findings showed that PDYN rs910080 T>C variant significantly increased the risk of heroin dependence (OR=7.91, 95%CI=3.36-18.61, P<0.0001, CC vs TT; OR=7.53, 95%CI=3.30-17.16, P<0.0001, CC vs TT+TC; OR=1.75, 95%CI=1.33-2.32, p<0.0001, C vs T). The rs2235749 C>T, rs2281285 A>G and 68bp VNTR variants of PDYN gene were not associated with heroin dependence. Altogether, our results provide an association between rs910080 polymorphism of PDYN gene and risk of heroin dependence in a sample of the southeast Iranian population.

Association of Single Nucleotide Polymorphisms of the MDM4 Gene With the Susceptibility to Breast Cancer in a Southeast Iranian Population Sample.

INTRODUCTION: The murine double minute 4 (MDM4) protein is a negative regulator of p53, and its upregulation has been observed in many tumor types. Previous literature suggested that genetic variations in the MDM4 gene are associated with risk of different cancers. The objective of the present study was to examine the effect of 3 common genetic variants of MDM4, rs4245739 A>C, rs11801299 G>A, and rs1380576 C>G, on the risk of breast cancer (BC) in a southeast Iranian population sample. PATIENTS AND METHODS: A total of 265 BC patients and 221 healthy women were included in this case-control study. We used polymerase chain reaction (PCR)-restriction fragment length polymorphism and tetra amplification refractory mutation system-PCR methods for detection of MDM4 polymorphisms. RESULTS: Our findings showed that rs1380576 C>G was associated with a reduced risk of BC using co-dominant (GC vs. CC: odds ratio [OR], 0.54; 95% confidence interval [CI], 0.34-0.84; P = .006; and GG vs. CC: OR, 0.49; 95% CI, 0.26-0.94; P = .044), dominant (CG+GG vs. CC: OR, 0.54; 95% CI, 0.35-0.82; P = .004), and allele models (G vs. C: OR, 0.74; 95% CI, 0.57-0.96; P = .025). However, our study failed to show any relationship between rs4245739 A>C and rs11801299 G>A variants and BC risk (P > .05). We also found no significant association between MDM4 variants and clinical characteristics of BC patients (P > .05). CONCLUSION: Our findings proposed that the MDM4 rs1380576 C>G polymorphism was a protective factor for BC risk in our population. Additional studies with larger sample sizes and diverse ethnicities are required to confirm our findings.

KRAS Gene Polymorphisms and their Impact on Breast Cancer Risk in an Iranian Population

Single nucleotide polymorphisms (SNPs) in the let-7 miRNA binding site within the 3' untranslated region (3'UTR) of KRAS appear related to the risk of cancer. The present case-control study was conducted with 244 BC patients and 204 healthy women to examine whether KRAS polymorphisms (rs61764370 T/G and rs712 G/T) are associated with breast cancer (BC) risk in an Iranian population. The polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping of KRAS SNPs. Our results showed that the rs61764370 TG genotype (OR= 3.73; 95% CI =1.38-10.08; P=0.007) as well as the G allele OR= 3.56; 95% CI =1.33-9.53; P=0.008, respectively) increased the risk of BC. However, the KRAS rs712 TT vs GG+GT genotype in a recessive model was associated with a reduced risk of BC (OR= 0.56; 95% CI =0.38-0.84; P=0.006). In addition, the rs712 T allele decreased the risk of BC compared with the G allele (OR=0.75, 95%CI=0.58-0.97, P=0.031). However, we found no relationship among KRAS SNPs and clinicopathological characteristics of BC patients (P>0.05). Taken together, the present study provided evidence of relationships between KRAS polymorphisms and BC risk in a southeast Iranian population. Additional studies using larger sample sizes and diverse ethnicities are now warranted.

FEN1 -69G>A and +4150G>T polymorphisms and breast cancer risk.

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.

Association Between Vascular Endothelial Growth Factor Gene Polymorphisms with Breast Cancer Risk in an Iranian Population.

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.

Evaluation of the pri-miR-34b/c rs4938723 polymorphism and its association with breast cancer risk.

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.