The MMP-2 -735 C Allele is a Risk Factor for Susceptibility to Breast Cancer

Yari, Kheirollah,Rahimi, Ziba,Moradi, Mohamad Taher,Rahimi, Zohreh Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.15

Background: The expression of MMP genes has been demonstrated to be associated with tumor invasion, metastasis and survival rate for a variety of cancers. The functional promoter polymorphism MMP-2 C-735T is associated with decreased expression of the MMP-2 gene. The aim of present study was to detect any association between MMP-2 C-735T and susceptibility to breast cancer. Materials and Methods: The MMP-2 C-735T polymorphism was studied in 233 women (98 with breast cancer and 135 healthy controls). All studied women were from Kermanshah and Ilam provinces of Western Iran. The MMP-2 C-735T polymorphism was detected using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: The frequencies of MMP-2 CC, CT and TT genotypes in healthy individuals were 59.3, 38.5 and 2.2%, respectively. However, in breast cancer patients, only CC (71.4%) and CT (28.6%) genotypes were observed (p=0.077). In patients the frequency of the MMP-2 C allele was significantly higher (85.7%) compared to that in controls (78.5 %, p=0.048). The presence of C allele of MMP-2 increased the risk of breast cancer by 1.64-fold [OR=1.64 (95%CI 1.01-2.7, p=0.049)]. The frequency of MMP-2 C allele was also higher in patients ${\leq}40$ years (88.9%) than those aged ${\geq}41$ years (67.5%, p=0.07). In addition, the frequency of MMP-2 C allele tended to be higher in patients with a family history of cancer in first-degree relatives (76.6%) compared to that without a family history of cancer (67.3%, p=0.31). Conclusions: Our findings indicate that the C allele of MMP-2 C-735T polymorphism is associated with increased risk of breast cancer. Also, the MMP-2 C allele might increase the risk of young onset breast cancer in our population.

IL-1B (C+3954T) Gene Polymorphism and Susceptibility to Gastric Cancer in the Iranian Population

Ismaili, Ahmad,Yari, Kheirollah,Moradi, Mohammad-Taher,Sohrabi, Maryam,Kahrizi, Danial,Kazemi, Elham,Souri, Zahra Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.2

Background: Gastric cancer as one of the most important diseases affecting health in all worldwide. Current studies have confirmed associations of cytokine gene polymorphisms with the risk of gastric cancer development. The current research aimed to assess the association of IL-1B+3954 genotypes with the risk of gastric cancer in the Iranian population. Materials and Methods: This case-control study covered 49 gastric cancer patients compared to 53 cancer free individuals as a control group. Genomic-DNA extraction was carried out from bioptic samples of patients and peripheral blood of healthy volunteers. Polymorphism of IL-1B +3954 genotypes were analysed with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: The frequencies of IL-1B +3954 A1A1, A1A2 and A2A2 genotypes in healthy individuals were 26.4, 66 and 7.6 %, respectively. However, in gastric cancer patients, A1A1, A1A2 and A2A2 with 4.1, 51 and 44.9% were observed (p<0.05). Conclusions: The findings of our results show a positive association between the IL-1B+3954 genotype distribution and the risk of gastric cancer disease in the Iranian population.

The first review study on association of DNA methylation with gastric cancer in Iranian population

Shahbazi, Mahsa,Yari, Kheirollah,Rezania, Niloufar Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.5

Background: Gastric cancer (GC) is the second leading cause of cancer-related death worldwide. Several environmental, genetic and epigenetic factors have been suggested to have a role in GC development. Epigenetic mechanisms like histone changes and promoter hyper-methylation are now being increasingly studied. Associations between methylation of many gene promoters with the risk of gastric cancer have been investigated worldwide. Such aberrant methylation may result in silencing of specific genes related to cell cycling, cell adhesion, apoptosis and DNA repair. Thus this molecular mechanism might have a key role in proliferation and migration of cancerous cells. Materials and Methods: In this review article we included studies conducted on DNA methylation and gastric cancer in Iranian populations. Using Science direct, Pubmed/PMC, Springer, Wiley online library and SciELO databases, all published data until 31 January 2016 were gathered. We also searched Science direct data base for similar investigations around the world to make a comparison between Iran and other countries. Results: By searching these databases, we found that the association between methylation of seven gene promoters and gastric cancer had been studied in Iran until 31 January 2016. These genes were p16, hLMH1, E-cadherin, CTLA4, $THR{\beta}$, mir9 and APC. Searching in science direct database also showed that 92 articles had been published around the world till January 2016. Our investigation revealed that despite the importance of GC and its high prevalence in Iran, the methylation status of only a few gene promoters has been studied so far. More studies with higher sample numbers are needed to reveal the relation of methylation status of gene promoters to gastric cancer in Iran. Conclusions: Further studies will be helpful in identifying associations of DNA methylation in candidate genes with gastric cancer risk in Iranian populations.

Manganese Superoxide Dismutase (MnSOD Val-9Ala) Gene Polymorphism and Susceptibility to Gastric Cancer

Moradi, Mohammad-Taher,Yari, Kheirollah,Rahimi, Zohreh,Kazemi, Elham,Shahbazi, Mehrdad Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.2

Background: Oxidative stress caused by the generation of reactive oxygen species plays an important role in human carcinogenesis. Manganese superoxide dismutase (MnSOD) Val-9Ala in the mitochondrial target sequence is the best known polymorphism of this enzyme. The purpose of the current research was to assess the association of MnSOD Val-9Ala genotypes with the risk of gastric cancer. Materials and Methods: This case-control study covered 54 gastric cancer patients compared to 100 cancer free subjects as controls. Extraction of DNA was performed on bioptic samples and genotypes were identified with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: The frequencies of MnSOD Ala/Ala, Ala/Val and Val/Val genotypes in healthy individuals were 24.3, 66.7 and 9%, respectively. However, in gastric cancer patients, Ala/Ala, Ala/Val and Val/Val were observed in 24.0, 48.0 and 28.0% (p=0.01). In patients the frequency of MnSOD Val allele was higher (52%) compared to that in controls (42%). Conclusions: The results of this study show a positive association between MnSOD Val-9Ala gene polymorphism and risk of gastric cancer disease in Iranian population.

The GPX1 Pro198Leu polymorphism in gastric cancer patients with and without Helicobacter pylori infection

Mohammad‑Taher Moradi,Kheirollah Yari,Zohreh Rahimi 한국유전학회 2017 Genes & Genomics Vol.39 No.11

Helicobacter pylori infection could induce oxidative stress. Oxidative stress is involved in the pathogenesis of gastric diseases. Glutathione peroxidase 1 (GPX1), is part of the enzymatic antioxidant defense, preventing oxidative damage. The aim of the present study was to assess the association of GPX1 Pro198Leu genotypes with gastric cancer in patients with and without H. pylori infection in a population of Northern Iran. The present case-control study consisted of 50 patients with gastric cancer and 78 cancer-free subjects as controls. Extraction of DNA was performed on bioptic samples and the GPX1 genotypes were identified using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The frequencies of GPX1 Pro/Pro, Pro/Leu and Leu/Leu genotypes in controls were 21.8, 71.8 and 6.4%, respectively. However, in gastric cancer patients, the frequencies of 34, 56 and 10% were observed for Pro/Pro, Pro/Leu and Leu/Leu genotypes, respectively (p = 0.185). In 38 (76%) patients infected with H. pylori, the frequencies of Pro and Leu alleles were 94.7 and 3.3%, respectively. There was a higher frequency of combined genotype of Pro/Leu + Leu/ Leu (94.7%) in H. pylori positive patients than that in patients without H. pylori infection (75%, p = 0.047). The presence of this genotype tended to increase the risk of H. pylori related gastric cancer by 5.88–fold (p = 0.069) in our population. Our findings indicated the absence of association between the GPX1 Pro198Leu polymorphism and the risk of gastric cancer in an Iranian population. However, we detected an association between H. pylori related gastric cancer with GPX1 Pro/Leu + Leu/Leu genotype.