Colorectal Cancer In Iranian Population Research Articles

Oxidative balance score and dietary phytochemical index can reduce the risk of colorectal cancer in Iranian population

BackgroundNo previous study has assessed the association between oxidative balance score (OBS) and dietary phytochemical index (DPI) with colorectal cancer (CRC) simultaneously. Therefore, this study investigated the association between OBS and DPI with the odds of CRC among the Iranian population.MethodsThis hospital-based age and sex-matched case–control study was conducted between September 2008 and January 2010 (142 controls and 71 cases were entered for analysis). New diagnosed CRC cases were selected from the Cancer Institute, Imam Khomeini Hospital of Tehran. Dietary intakes were determined by a semi-quantitative food frequency questionnaire (FFQ). Then, dietary indices were calculated by food items and nutrient intake. Logistic regression was utilized for assessing the tertiles of OBS and DPI.ResultsIn multivariate analysis, OBS was associated with a 77% reduction in CRC odds in the last tertile than the first tertile (odds ratio (OR) = 0.23, confidence interval (CI): 0.07–0.72, Ptrend = 0.017). Also, we found a 64% reduction in CRC odds in the last tertile of DPI compared to the first tertile (OR = 0.36, CI: 0.15–0.86, Ptrend = 0.015).ConclusionsA diet rich in phytochemicals and anti-oxidants, including fruits and vegetables (citrus fruits, colored berries, and dark-green leafy vegetables) and whole grains, may reduce the CRC odds.

Antibiotic resistance, phylogenetic group, and genotyping investigation in Escherichia coli strains of gut flora in patients with colorectal cancer in Iranian population

Background: According to the World Health Organization, the prevalence of colorectal cancer (CRC) is the third-most common cancer in Iran. The population of Escherichia coli strains of the B2 phylogenetic group as one of the components of gut microbiota is increased in the gut of people with CRC and can also play a role in the process of cancerous intestinal cells or malignancy. The most common concern about treating infections and their association with cancer is multidrug resistance (MDR). Methods: In this study, stool samples of 20 patients with CRC were examined for sensitivity to 9 antibiotics and their genotypes were determined. Results: More than 90% of the isolates were MDR. Although among 20 isolates of E. coli gut flora in CRC patients, 11 (55%), 7 (35%), 0 (0%), and 2 (10%) strains belonged to phylogenetic groups B2, D, B1, and A, respectively. Conclusions: There was no significant relationship between the B2 phylogenetic group and MDR. Furthermore, the closeness of the species based on >90% similarity, seven clusters were observed that among five clusters, similarities were observed in terms of the phylogenetic group.

Association of Epidermal Growth Factor 61A>G, Survivin -31G>C, and EFNA1 -1732G>A Polymorphisms with Susceptibility to Colorectal Cancer.

Genetic polymorphisms play an important role in the development of colorectal cancer (CRC). Functional variants in the epidermal growth factor (EGF), survivin, and Ephrin A1 (EFNA1) genes have been previously reported to play a potential role in susceptibility to CRC, but these polymorphisms have not been well replicated. The aim of this study was to assess the association of the EGF 61A>G, Survivin -31G>C, and EFNA1 -1732G>A polymorphisms with the susceptibility to CRC in an Iranian population. A total of 148 cases diagnosed with CRC and 160 healthy subjects were recruited. The EGF 61A>G, survivin -31G>C, and EFNA1 -1732G>A polymorphisms were genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Our data revealed that the homozygous mutant genotype (CC: OR = 2.895, 95% CI = 1.092-7.673, p = 0.033) and mutant allele (C: OR = 1.629, 95% CI = 1.152-2.303, p = 0.006) of the survivin -31G>C were associated with an increased risk of CRC in the Iranian population. However, our results failed to show an association between the EGF 61A>G and EFNA1 -1732G>A polymorphisms and CRC risk. Our results revealed that the survivin -31G>C polymorphism might play an important role in development of CRC in Iranian population. However, no association of EGF 61A>G and EFNA1 -1732G>A polymorphisms with CRC risk was found.

Association study of TAAAA polymorphism in the first intron of p53 gene with risk of colorectal cancer in Iranian population

BackgroundColorectal cancer is the most common gastrointestinal cancer and the third most common cancer over the world. Genetic mutations in the p53 gene are associated with tumorigenesis of most cancers. So far, no study has been conducted on the association between TAAAA repeats in the first intron of the p53 gene and risk of colorectal cancer. In this study, we investigated the association of the TAAAA polymorphism in the first intron of p53 gene with colorectal cancer. We evaluated p53 gene polymorphism in 151 patients with colorectal cancer and a control group of 180 healthy individuals. For TAAAA repeat polymorphism evaluation, we used conventional polymerase chain reaction (PCR) to amplify the desired sequence and the number of TAAAA repeats was specified by polyacrylamide gel electrophoresis and direct sequencing.ResultsIn the present study, 5 different alleles of TAAAA repeat with 6–10 repeats and 13 allele genotypes were determined between cases and controls. The most frequent allele in both controls (59.8%) and cases (57.6%) was the 8 repeats of TAAAA. Results of homozygous genotypes equal or lower than 8 repeats are higher among the healthy individuals than among the cases. In contrast, the number of genotypes equal or higher than 9 (9.10, 9.9) was higher among the colorectal cancer patients. Because of the small size of the studied population, the statistical analysis did not demonstrate a significant relationship. Also, there is no significant association between genotype, metastasis, and age.ConclusionOur observations did not show a significant association between the TAAAA repeat polymorphism in the first intron of the p53 gene and the colorectal cancer risk.

Investigating the Association Between miR-608 rs4919510 and miR-149 rs2292832 with Colorectal Cancer in Iranian Population.

Single Nucleotide Polymorphisms (SNPs) in microRNA (miRNA) networks may serve as diagnostic and prognostic biomarkers of a variety of diseases such as cancer. Some studies have been performed to examine associations between miR-149 and miR-608 polymorphisms and susceptibility to colorectal cancer, but the results remain controversial and race-dependent. The aim of our study was to investigate the association of miR-608 (rs4919510) and miR- 149 (rs2292832) with colorectal cancer and its clinical features in a sample of Iranian population. This retrospective study was conducted on 76 CRC cases and 70 controls. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) method. To confirm the RFLP process, 10% of the PCR products were validated by direct sequencing. Our findings showed significant correlation between adjusted data of rs2292832 with sex and age in TT genotype (OR= 5.148, 95% CI=1.081 ± 24.511, P=0.04). Distribution of rs4919510 polymorphism was not significantly different between controls and patients (CG, adjusted OR= 1.243, 95% CI=0.546 ± 2.831; P=0.604 and GG, adjusted OR= 0.249, 95% CI=0.063 ± 0.959; P=0.05). On the other hand, our results showed that a significant correlation was present between metastatic clinicopathological features and miR-608 (rs4919510) polymorphism (P=0.044). Our findings reveal that genotypes of rs2292832 and rs4919510 are not associated with risk of colorectal cancer in Iranian population. Moreover, the CC genotype of rs4919510 contributes to the metastatic features of the colorectal cancer.

Single nucleotide polymorphism rs4648298 in miRNAs hsa-miR21 and hsa-miR590 binding site of COX gene is a strong colorectal cancer determinant.

Genetic determinants are considered as driving forces in development colorectal cancer (CRC), a malignancy that ranks as the second cause of cancer death in the world. Single nucleotide polymorphisms (SNPs), are considered as the main genetic factor in cancers susceptibility. MicroRNAs are critical players in posttranslational gene regulation by binding to their specific recognition sequences located at 3' untranslated region (UTR) of mRNAs. In present study we have elucidated the role of 9,850 A > G (rs4648298), in development of sporadic CRC in Iranian population. A case-control study using 88 CRC patients and 88 noncancerous counterparts was undertaken in order to determine rs4648298 genotypes using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Also, a meta-analysis was performed based on 9 articles accessed via the MEDLINE, Cochrane review, Google Scholar and Scopus databases. AA genotype was determined to be associated with significant decreased risk of CRC in our study population [odds ratio (OR) =0.14; 95% confidence interval (CI), 0.05-0.34; P<0.001]. In a meta-analysis on 6 risk estimates for the AG versus AA genotype, we found a significant inverse association between AG SNPs and risk of gastric adenocarcinoma, CRC, breast cancer and prostate cancer (OR =0.86; 95% CI, 0.76-0.98; P<0.02). Our results suggest significant correlation between rs4648298 polymorphism and CRC risk in Iranian population.

MIR196A2 rs11614913 contributes to susceptibility to colorectal cancer in Iranian population: A multi-center case-control study and meta-analysis

Maturation of MIR196A2 as a gene regulator with a high potential for targeted cancer therapy can be modulated by the rs11614913 polymorphism. Several studies evaluating the association between this variant and pathogenesis of colorectal cancer (CRC) found significant results in various ethnic groups. This study aimed at investigating this relationship in a large sample size of Iranians as well as in a systematic review and meta-analysis of the pooled data of the current study with previous reports from Iran and other populations. After extraction of genomic DNA from the formalin-fixed paraffin-embedded tissues and whole blood of 2150 subjects (42% CRC patients), the rs11614913 was genotyped in both cases and controls. Furthermore, we conducted a meta-analysis of the present case-control study together with a previous report from Iranian population. The results of case-control study identified significant association between the rs11614913 and susceptibility to CRC [TT vs. CC: 1.58 (1.26–1.98), p < 0.01; TT vs. CT: 3.94 (3.07–5.05), p < 0.01; TT vs. CC + CT: 0.70 (0.59–0.83), p < 0.01; and CT + TT vs. CC: 1.43 (1.21–1.70), p < 0.01]. After correction of the meta-analysis results by using Bonferroni protocol, no significant association was observed in overall and in Asians [T vs. C: 1.19 (1.00–1.43), p = 0.05 and 1.14 (0.83–1.56), p = 0.43, respectively], whereas association was significant in Caucasians [T vs. C: 1.14 (1.04–1.25), p = 0.004] influenced by the data from Iran [T vs. C: 1.15 (1.03–1.29), p = 0.02 and TT vs. CC + CT: 0.73 (0.60–0.87), p = 0.003]. In conclusion, MIR196A2 rs11614913 might play a potential role in the pathogenesis of CRC in Iranian population.

RAD51 135G&gt;C polymorphism and risk of sporadic colorectal cancer in Iranian population

Colorectal cancer (CRC) is among the most common cancers and accounts as the second leading cause of death from cancers in the world. RAD51 plays a crucial role in double-strand breaks repair of DNA. Single nucleotide polymorphisms within this gene could influence on the potential of DNA repair and in consequence on the susceptibility to various tumors such as CRC. This is the first report about the role of RAD51 polymorphisms in Iranian CRC susceptibility. The study was conducted to evaluate the association of 135G>C polymorphism of RAD51 gene with sporadic CRC in a subset of Iranian population. The current case-control study was performed from 2013 to 2015. One hundred patients with sporadic CRC and one hundred controls were enrolled from two referral centers in Isfahan. All samples were genotyped for the RAD51 gene using polymerase chain reaction-restriction fragment length polymorphism assay. The results revealed no significant association between the RAD51 135G>C and sporadic CRC (odds ratio = 0.86, 95% confidence interval = 0.464-1.595). The frequency of genotypes and also alleles of the mentioned polymorphism were not significantly different between case and control groups (P = 0.2 and 0.4, respectively). The results suggest that RAD51 135G>C probably has not a crucial role in Iranian CRC risk and is not an important potential risk factor in molecular diagnostics of mentioned disease among Iranian population.

Lack of association of CASC8 rs1447295 with colorectal cancer in Iranian population: A multicenter case-control study

Several studies reported the potential role of the rs1447295 polymorphism in susceptibility to cancer. This variant located in the cancer susceptibility candidate 8 (CASC8) is a long noncoding RNA (lnRNA) gene and does not code protein. LnRNA transcripts play a potential regulatory role in the expression of key genes involved in multiple cellular pathways, including cell cycle, pluripotency, and immune response. The aim of this study is to evaluate this association with colorectal cancer (CRC) in a large case-control study of the Iranian population. After extraction of genomic DNA by the standard protocols, the rs1447295 was genotyped in 2416 subjects (46% patients). Results of this case-control demonstrated no significant association between the rs1447295 polymorphism and risk of CRC or its characteristics under allele or alternative genotype models. In conclusion, it is unlikely that the rs1447295 polymorphism is a risk variant for the development of CRC in Iranian population.

MTRR rs1801394 and its interaction with MTHFR rs1801133 in colorectal cancer: a case-control study and meta-analysis.

This study aims to evaluate the association between the MTRR rs1801394 alone or in interaction with the MTHFR rs1801133 and susceptibility to colorectal cancer (CRC) and its characteristics in Iranian population. Additionally, both a systematic review and meta-analysis were performed to derive a more precise assessment of this association. Genomic DNA of 2332 subjects was genotyped for rs1801394. These data were pooled with 17 eligible studies for meta-analysis. No significant association was found between the rs1801394 or rs1801394-rs1801133 and CRC risk. Meta-analysis results also demonstrated no significant relationship between the rs1801394 and CRC risk. Results of this study showed that the rs1801394 alone or together with the rs1801133 is not a risk factor for CRC in Iranian population.

Single Nucleotide Polymorphism (A870G) of the CCND1gene: association with colorectal cancer susceptibility.

The aim of this study is to demonstrate the role of CCND1 gene polymorphism, A870G, in susceptibility to sporadic colorectal cancer in Iranian population. It has been distinguished that CCND1 gene is one of the main genes in Wnt signaling pathway which involves in generating colorectal cancer. Nonetheless, there is no consistent result in terms of association between the genetic variations of this gene and colorectal cancer risk. We designed a case-control study consisting of 100 subjects with colorectal cancer (CRC) and 100 healthy controls to investigate the effect of A870G polymorphism on CRC susceptibility in an Iranian population. Genotype determination was performed by PCR-RFLP method. The frequency of GG, AG and AA genotypes for cases were 24%, 51% and 25% respectively, while the genotype frequency for controls were 21%, 50% and 29% respectively. It was identified that there is no significant association between A870G polymorphism and risk of CRC, even after adjusting sex, age and smoking status variables (P = 0.777; OR=1.32 95% CI: 0.6-2.93).. Despite the well-known role of CCND1 gene in cell cycle regulation, our results revealed that A870G polymorphism could not be a potential predisposing risk factor in genetic susceptibility to CRC, at least in the studied population.

MTHFR rs1801133 polymorphism and susceptibility to colorectal cancer in Iranian population: evidence of a case-control study and meta-analysis.

The purpose of this study was to investigate this hypothesis in a case-control study and meta-analysis in Iranian population. This polymorphism was genotyped in the 2421 subjects (46% CRC patients) from Tehran. Meta-analysis was performed for determining the risk effect size of this polymorphism on CRC. Both case-control study and meta-analysis showed no association between rs1801133 and CRC risk or its features. This study failed to identify an association between the rs1801133 and susceptibility to CRC in Iranian population.

Single Nucleotide Polymorphism (K589E) of the EXO1 Gene: Association with Colorectal Cancer Susceptibility and Clinicopathological Features

Background and aim: Exonuclease1 (EXO1) is a member of the RAD2 nuclease family which is involved in mismatch repair (MMR) system and contributes to the maintenance of genomic stability, modulation of DNA recombination and cell cycle arrest mediation. K589E (rs1047840) as a potentially functional polymorphism in EXO1 gene may alter cancer risk by influencing its repair activity. Method: We designed a case-control study consisting of 319 subjects with colorectal cancer (CRC) and 310 healthy controls to investigate the effect of K589E polymorphism on CRC susceptibility and clinicopathological features in an Iranian population. Genotype determination was performed by PCR-RFLP method. Results: We provided the first evidence that there is not any significant association between EXO1 K589E alleles and genotypes and risk of CRC, even after adjustment for sex, age and smoking status (OR=1.033; 95% CI 0.814-1.312). Also analysis of clinicopathological characteristics and genotype distribution did not show any significant correlation. Conclusion: Despite the well-known role of EXO1, our results revealed that EXO1 K589E polymorphism could not be a potential predisposing risk factor in genetic susceptibility to CRC, at least in the studied population. A large scale case-control study will need to be carried out to further validate this polymorphism as a non- contributor to the risk of CRC in Iranian population.

“Letter to editor” in lieu of article published in Mol Biol Rep. 2012 May; 39(5):5219–24. PTGS2 (COX2) −765G&gt;C gene polymorphism and risk of sporadic colorectal cancer in Iranian population

Dear Editor Recently, I read an article with great interest published by Daraei et al., which was appeared in your journal as Daraei et al., 2012 (May; 39(5):5219–5224). The study aimed to evaluate the impact of the COX2 gene -765 G[C polymorphism on sporadic colorectal cancer risk. Though, the study provides preliminary evidence to consider COX2 polymorphism as a risk factor for sporadic colorectal cancer. But, after careful reading of the article, few important issues came out which must be addressed for further actions. First, it appears that the authors somehow missed the statistical power in this study. Sample sizes remain a major issue in genetic case–control studies analyzing the association of polymorphism with disease susceptibility. Hence, the study should obtain an adequate statistical power to estimate significant association accurately, which remains a primary criterion to perform such studies. Underpowered studies usually lead to false positive associations and misinterpretations [1]. The authors failed to mention the incidence rate of sporadic colorectal cancer in the said study. The number of patients and controls recruited in the present study achieved the required statistical power is questionable and did not discuss in the text. Second, in Table 2, the percentage of genotype did not reveal 100 % in sporadic colorectal cancer patients. All these points suggest a thorough examination of the association observed in the said study, and must be clarified before concluding that COX2 gene polymorphism is a potential marker of sporadic colorectal cancer.

PTGS2 (COX2) −765G&gt;C gene polymorphism and risk of sporadic colorectal cancer in Iranian population

Colorectal cancer (CRC) is one of the leading cancers worldwide. Through genome wide association studies, several single nucleotide polymorphisms scattered in the genome emerged to be influential in the development of sporadic CRC in some populations. However, replicative studies failed to prove a particular SNP-CRC association in populations and ethnic groups. Cyclooxygenase-2 (PTGS2) is a crucial enzyme involved in the metabolism of prostaglandins. The aim of this replicative study is to investigate the possible association between PTGS2-765G>C polymorphism and sporadic CRC risk in a subset of Iranian population. A total of 110 patients with sporadic CRC, and 120 controls were genotyped for PTGS2-765G>C polymorphism by using polymerase chain reaction-based restriction fragment length polymorphism. There were no significant differences in the genotype and allele frequencies of PTGS2-765G>C between two groups except in irregular aspirin or non-steroidal anti-inflammatory drugs (NSAID) consumers. Frequencies of genotypes and alleles were as follows: GG=44.2, GC=48.3, CC=7.5%, in controls and GG=34.55, GC=60.9, CC=4.55% in cases. Regarding the allele frequency, the following values were found: G=65, C=35% in cases and 68.3, 31.7% in the controls, respectively. In irregular aspirin or NSAID consumers combined GC+CC genotype was found to be a risk genotype (OR=1.933, 95% CI: 1.067-3.501, P=0.036). Overall, no significant relation was found between this polymorphism and sporadic CRC in Iranians. However, in irregular aspirin or NSAID consumers the combined GC+CC genotype proved to be a risk genotype.

Erratum to: Effect of rs6983267 polymorphism in the 8q24 region and rs4444903 polymorphism in EGF gene on the risk of sporadic colorectal cancer in Iranian population

Erratum to: Effect of rs6983267 polymorphism in the 8q24 region and rs4444903 polymorphism in EGF gene on the risk of sporadic colorectal cancer in Iranian population

Effect of rs6983267 polymorphism in the 8q24 region and rs4444903 polymorphism in EGF gene on the risk of sporadic colorectal cancer in Iranian population

Colorectal cancer (CRC) is among the major causes of cancer-related morbidity, mortality, and human health problem worldwide. Single-nucleotide polymorphisms (SNPs) in different genes are reported to be effective in increased risk of CRC in different ethnic population. We conducted a case-control study in patients diagnosed with sporadic colorectal cancer (n = 115) and healthy controls based on colonoscopy evidences (n = 120).In this replicative study, we aimed to investigate the association of two previously reported polymorphisms, rs6983267 and rs4444903, with sporadic colorectal cancer in a subset of Iranian patients. Genotyping was performed via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. A significant relation was found between rs6983267 variant in the 8q24 region and colorectal cancer. The distribution of G/G genotypes among sporadic CRC patients was more frequent than that in the control group (P value = 0.001). The frequency of the G allele in the colorectal cancer patient group was also higher than that in the control group (65% vs. 48%; P value = 0.001). Compared with GG genotype, individuals with G/T and T/T genotypes had lower risk to develop sporadic CRC (OR = 0.357, 95% CI = 0.201-0.635). For the rs4444903 SNP, no significant association (P value = 0.149) was found with colorectal cancer risk. In conclusion, our findings suggest that the 8q24 rs6983267 SNP may play a pivotal role in the development of sporadic CRC in Iranian population. Therefore, it may be included as a potential genetic susceptibility marker for sporadic CRC.

Association of leptin receptor gene Gln223Arg polymorphism with susceptibility to colorectal cancer.

Leptin is a 16 kDa polypeptide hormone which secreted by adipose tissue and has an important role in energy balance, insulin pathway and inflammation, because of that it may play an important role in colorectal cancer (CRC). Leptin exerts its effect through the leptin receptor (LEPR) a member of the class I cytokine receptor family. We have investigated whether glutamine to arginine substitution (Gln223Arg) in exon 6 of the leptin receptor gene, has implications for susceptibility to CRC. Polymerase chain reaction (PCR) and restriction enzyme digestion (RFLP) was performed to evaluate the association between the Gln223Arg polymorphism of the LEPR and CRC risk in a case-control study in 346 subjects involving 173 cases with CRC and 173 controls. There was no statistically evidence of significant difference in genotype and allele frequencies between the cases with CRC and controls for the Gln223Arg polymorphism of LEPR, before or after adjusting for confounders (age, BMI, sex, and smoking status). Furthermore, no significant difference was observed between the CRC cases and controls by BMI, sex and smoking status. Our findings suggest that the LEPR Gln223Arg polymorphism is not associated with the risk of CRC in Iranian population.

Amino acid substitution polymorphisms of two DNA methyltransferases and susceptibility to sporadic colorectal cancer

Aim: To evaluate the association of DNMT1 and MGMT amino acid substitution polymorphisms and colorectal cancer in Iranian population. Background: The MGMT and DNMT1 are two important methyltransferase enzymes. Amino acid substitution polymorphisms in MGMT and DNMT1 genes may be associated with the genetic susceptibility to sporadic colorectal cancer. Patients and methods: We assessed eight non-synonymous polymorphisms of these two genes by PCR/Pyrosequencing. Our population consisted of 208 individuals with sporadic colorectal cancer and 213 controls. Allele frequencies and genotypes were compared between the cases and controls. Results: Odds ratios were calculated and there was no association between DNMT1 and colorectal cancer. However, there was a significant association between two polymorphisms with sporadic colorectal cancer; Arg128Gln (OR 5.53, 95%CI 2.58-7.16) and Gly160Arg (OR 3.04, 95%CI=1.48-6.31) of MGMT gene. Conclusion: This finding could be an accurate indicator of high occurrence of colorectal cancer in Iranian patients.