• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2647-2650
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• 2014

Background: Colorectal cancers(CRC) are the third most common cancer in the western world, with surgery preferred for management of non-metastatic disease and post surgical treatment usually arranged according to the TNM staging system. However, there is still prognostic variation between patients who have the same stage. It is increasingly recognized that variations within disease course and clinical outcome in colorectal cancer patients are influenced by not only oncological characteristics of the tumor itself but also host response factors. Recent studies have shown correlation between the inflammatory response and clinical outcomes in various cancers. The neutrophil/lymphocyte ratio (NLR) has been described as a marker for immune response to various stimuli including cancer. Material-Methods: Two hundred eighty-one CRC patients were included in our retrospective analysis, separated into two groups according to a cut-off value for the NLR. Patient data including age, gender, vertical penetration, anatomic location, and differentiation of the tumor, TNM stage, survival rate, and disease-free survival were analyzed for correlations with the NLR. Results: Using ROC curve analysis, we determined a cut-off value of 2.2 for NLR to be best to discriminate between patient survival in the whole group. In univariate analysis, high pretreatment NLR (p=0.001, 95%CI 1.483-4.846), pathologic nodal stage (p<0.001, 95%CI 1.082-3.289) and advanced pathologic TNM stage (p<0.001, 95%CI 1.462-4.213) were predictive of shorter survival. In multivariate analysis, advanced pathologic TNM stage (p=0.001, 95%CI 1.303-26.542) and high pretreatment NLR (p=0.005, 95%CI 1.713-6.378) remained independently associated with poor survival. Conclusions: High pre-treatment NLR is a significant independent predictor of shorter survival in patients with colorectal cancer. This parameter is a simple, easily accessible laboratory value for identifying patients with poorer prognosis.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6035-6039
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• 2014

Background: Substantial evidence from epidemiological studies has suggested that increased levels of calcium may play a protective role against colorectal cancer (CRC). Given the vital role of calcium sensing receptor (CaSR) and parathyroid hormone (PTH) in the maintenance of calcium homeostasis, we explored whether the rs1801725 (A986S) variant located in exon 7 of the CaSR gene and the rs6256 variant located in exon 3 of PTH gene might be associated with CRC risk. Materials and Methods: In this study 860 subjects including 350 cases with CRC and 510 controls were enrolled and genotyped using PCR-RFLP methods. Results: We observed no significant difference in genotype or allele frequencies between the cases with CRC and controls for both CaSR and PTH genes either before or after adjustment for confounding factors including age, BMI, sex, smoking status, and family history of CRC. Furthermore, no evidence for effect modification of any association of rs1801725 and rs6256 variants and CRC by BMI, sex, or tumor site was observed. In addition, there was no significant difference in genotype and allele frequencies between the normal weight (BMI < $25kg/m^2$) cases and overweight/obese (BMI ${\geq}25kg/m^2$) cases for the two SNPs. Conclusions: These data indicated that the CaSR gene A986S variant is not a genetic contributor to CRC risk in the Iranian population. Furthermore, our results suggest for the first time that PTH gene variant does not affect CRC risk. Nonetheless, further studies with larger sample size are needed to validate these findings.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.3287-3291
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• 2014

Background: The interesting preponderance of Chinese with colorectal carcinoma (CRC) amongst the three major ethnic groups in Malaysia prompted a study to determine DNA mismatch repair (MMR) status in our CRC and attempt correlation with patient age, gender and ethnicity as well as location, grade, histological type and stage of tumour. Histologically re-confirmed CRC, diagnosed between $1^{st} $January 2005 and $31^{st}$ December 2007 at the Department of Pathology, University of Malaya Medical Centre, were immunohistochemically stained with monoclonal antibodies to MMR proteins, MLH1, MSH2, MSH6 and PMS2 on the Ventana Benchmark XT autostainer. Of the 142 CRC cases entered into the study, there were 82 males and 60 females (M:F=1.4:1). Ethnically, 81 (57.0%) were Chinese, 32 (22.5%) Malays and 29 (20.4%) Indians. The patient ages ranged between 15-87 years (mean=62.4 years) with 21 cases <50-years and 121 ${\geq}50$-years of age. 14 (9.9%) CRC showed deficient MMR (dMMR). Concurrent loss of MLH1 and PMS2 occurred in 10, MSH2 and MSH6 in 2 with isolated loss of MSH6 in 1 and PMS2 in 1. dMMR was noted less frequently amongst the Chinese (6.2%) in comparison with their combined Malay and Indian counterparts (14.8%), and was associated with right sided and poorly differentiated tumours (p<0.05). 3 of the 5 (60.0%) dMMR CRC cases amongst the Chinese and 1 of 9 cases (11.1%) amongst the combined Malay and Indian group were <50-years of age. No significant association of dMMR was noted with patient age and gender, tumour stage or mucinous type.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7127-7131
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• 2013

The primary aim of this study was to evaluate the relationship of single nucleotide polymorphisms (SNPs) in ribosomal protein SA (RPSA) gene with colorectal cancer (CRC). A case-control study including 388 controls and 387 patients with CRC was conducted in a Chinese population. Information about socio-demography and living behavior factors was collected by a structured questionnaire. Three SNPs (rs2133579, rs2269349, rs7641291) in RPSA gene were genotyped by Illumina SnapShot method. Multiple logistic regression models were used for assessing the joint effects between tea consumption and SNPs on CRC. The subjects with rs2269349 CC genotype had a decreased risk for CRC (OR=0.60; 95%CI = 0.37-0.99), compared with TT/CT genotype after adjustment for covariates. A similar association of rs2269349 with rectal cancer was observed (OR=0.49; 95%CI=0.24-1.00). Further analyses indicated that this SNP could modify the protective effect of tea drinking on CRC. Among the subjects with rs2269349 TT/CT or rs2133579 AA/GA, there was a marginal significantly lower risk of CRC (OR and 95%CI: 0.63 and 0.39-1.01 for rs2269349; 0.64 and 0.40-1.02 for rs2133579) in tea-drinking subjects in comparison to non-tea-drinking subjects. Mutants in the RPSA gene might be associated with genetic susceptibility to CRC and influence the protective effect of tea consumption in the Chinese population.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3631-3634
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• 2013

MicroRNAs (MiRNAs) play important roles in coordinating a variety of cellular processes and abnormal expression has been linked to the occurrence of several cancers. The miRNA miR-451 is downregulated in colorectal carcinoma (CRC) cells, suggested by several research groups including our own. In this study, synthetic miR-451 mimics were transfected into the SW620 human CRC cell line using Lipofectamine 2000 and expression of miR-451 was analyzed by real time PCR, while expression of CAB39, LKB1, AMPK, AKT, PI3K and Bcl2 was analyzed by Western blot, and cell growth was detected by MTT assay. In comparison to the controls, a significant increase in the expression of miR-451 was associated with significantly decreased expression of CAB39, LKB1, AMPK, AKT, PI3K and Bcl2. The capacity of cell proliferation was significantly decreased by miR-451 expression, which also inhibited cell growth. Our study confirmed that miR-451 has a repressive role in CRC cells by inhibiting cell growth through down-regulating the P13K/AKT pathway.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3761-3768
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• 2013

Background: The Saudi population has experienced a sharp increase in colorectal and gastric cancer incidences within the last few years. The relationship between gene polymorphisms of xenobiotic metabolizing enzymes and colorectal cancer (CRC) incidence has not previously investigated among the Saudi population. The aim of the present study was to investigate contributions of CYP1A1, CYP2E1, and GSTM1 gene polymorphisms. Materials and Methods: Blood samples were collected from CRC patients and healthy controls and genotypes were determined by polymerase chain reaction restriction fragment length polymorphism and sequencing. Results and Conclusions: $CYP2E1^*6$ was not significantly associated with CRC development (odd ratio=1.29; confidence interval 0.68-2.45). A remarkable and statistically significant association was observed among patients with $CYP1Awt/^*2A$ (odd ratio=3.65; 95% confidence interval 1.39-9.57). The $GSTM1^*0/^*0$ genotype was found in 2% of CRC patients under investigation. The levels of CYP1A1, CYP2E1 and GSTM1 mRNA gene expression were found to be 4, 4.2 and 4.8 fold, respectively, by quantitative real time PCR. The results of the present case-control study show that the studied Saudi population resembles Caucasians with respect to the considered polymorphisms. Investigation of genetic risk factors and susceptibility gene polymorphisms in our Saudi population should be helpful for better understanding of CRC etiology.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1149-1154
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• 2014

Background: In Malaysia, data from the Malaysian Health Ministry showed colorectal cancer (CRC) to be the second most common type of cancer in 2007-2009, after breast cancer. The same was apparent after looking at males and females cases separately. In the present study, the Geographic Information System (GIS) was employed to describe the distribution of CRC cases in Kuala Lumpur (KL), Malaysia, according to socio-demographic factors (age, gender, ethnicity and district). Materials and Methods: This retrospective review concerned data for patients diagnosed with colorectal cancer in the years 1995 to 2011 collected from the Wilayah Persekutuan Health Office, taken from the cancer notification form (NCR-2), and patient medical records from the Surgical Department, Universiti Kebangsaan Malaysia Medical Centre (UKMMC). A total of 146 cases were analyzed. All the data collected were analysed using ArcGIS version 10.0 and SPSS version 19.0. Results: Patients aged 60 to 69 years accounted for the highest proportion of cases (34.2%) and males slightly predominated 76 (52.1%), Chinese had the highest number of registered cases at 108 (74.0%) and staging revealed most cases in the 3rd and 4th stages. Kernel density analysis showed more cases are concentrated up in the northern area of Petaling and Kuala Lumpur subdistricts. Spatial global pattern analysis by average nearest neighbour resulted in nearest neighbour ratio of 0.75, with Z-score of -5.59, p value of <0.01 and the z-score of -5.59. Spatial autocorrelation (Moran's I) showed clustering significant with p<0.01, Z score 3.14 and Moran's Index of 0.007. When mapping clusters with hotspot analysis (Getis-Ord Gi), hot and cold spots were identified. Hot spot areas fell on the northeast side of KL. Conclusions: This study demonstrated significant spatial patterns of cancer incidence in KL. Knowledge about these spatial patterns can provide useful information to policymakers in the planning of screening of CRC in the targeted population and improvement of healthcare facilities to provide better treatment for CRC patients.

• Asian Pacific Journal of Cancer Prevention
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• 제16권1호
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• pp.367-372
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• 2015

Background: Human adiponectin (ApN), a 30 kDa glycoprotein of 244-amino acids which is predominantly produced by adipocytes, exerts its effects via two receptors, namely adiponectin receptor-1 (adipo-R1) and adiponectin receptor-2 (adipo-R2) with differential binding affinity to globular adiponectin. Adiponectin receptor expression has been studied in several cancer tissues. However, there are no studies of colorectal adenomas which are considered to be precursors for colorectal carcinoma (CRC). Objectives: In the present study, the expression of adipo-R1 and adipo-R2 was investigated immunohistochemically in colorectal adenomas and colorectal carcinoma tissues in an attempt to determine associations with these tumors. Materials and Methods: The study enrolled 50 CRC patients with tumor resection and 82 patients who were diagnosed with adenomatous polyps, classified as negative for neoplasia, low-grade dysplasia (L-GD) or high- grade dysplasia (H-GD). Results: Expression of both adipo-R1 and adipo-R2 was found to be significantly lower in the CRCs than in colorectal adenomas (tubular and tubulovillous, p=0.009 and p<0.001, respectively). Adipo-R1 and adipo-R2 expression was also significantly lower in the CRC group when compared with the groups of patients with low grade dysplasia, high-grade dysplasia or no neoplasia (p=0.012 and p<0.001, respectively). In addition, it was observed that adipo-R2 expression was generally positive in the non-neoplastic group irrespective of the adipo-R2 expression. In the L-GD, H-GD and CRC groups, the adipo-R2 result was positive whenever adipo-R1 result was positive but some patients with negative adipo-R1 had positive adipo-R2 (p<0.001, p=0.004, p<0.001, respectively). Conclusions: This study indicated that ApN may play a role in the progression of colorectal adenomatous polyps to carcinoma through actions on adipo-R1 and adipo-R2 receptors.

• Molecules and Cells
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• 제42권11호
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• pp.755-762
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• 2019

Despite decades of research into colorectal cancer (CRC), there is an ongoing need for treatments that are more effective and safer than those currently available. Lactic acid bacteria (LAB) show beneficial effects in the context of several diseases, including CRC, and are generally regarded as safe. Here, we isolated a Lactobacillus rhamnosus (LR)-derived therapeutic protein, p8, which suppressed CRC proliferation. We found that p8 translocated specifically to the cytosol of DLD-1 cells. Moreover, p8 down-regulated expression of Cyclin B1 and Cdk1, both of which are required for cell cycle progression. We confirmed that p8 exerted strong anti-proliferative activity in a mouse CRC xenograft model. Intraperitoneal injection of recombinant p8 (r-p8) led to a significant reduction (up to 59%) in tumor mass when compared with controls. In recent years, bacterial drug delivery systems (DDSs) have proven to be effective therapeutic agents for acute colitis. Therefore, we aimed to use such systems, particularly LAB, to generate the valuable therapeutic proteins to treat CRC. To this end, we developed a gene expression cassette capable of inducing secretion of large amounts of p8 protein from Pediococcus pentosaceus SL4 (PP). We then confirmed that this protein (PP-p8) exerted anti-proliferative activity in a mouse CRC xenograft model. Oral administration of PP-p8 DDS led to a marked reduction in tumor mass (up to 64%) compared with controls. The PP-p8 DDS using LAB described herein has advantages over other therapeutics; these advantages include improved safety (the protein is a probiotic), cost-free purification, and specific targeting of CRC cells.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3085-3088
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• 2016

Background: Worldwide, colorectal cancer (CRC) is reported to be the fourth most common cancer in men and the third most common in women. KRAS is a proto-oncogene located on the short arm of chromosome 12. The aim of this study was to evaluate the KRAS oncogene and its relationship it with clinicopathologic features in 33 Kurdish patients. Materials and Methods: Metastatic CRC between 2012 and 2016 that came to Imam Reza hospital, Kermanshah province, Iran, were analysed for KRAS mutations using allele specific PCR primers and pyrosequencing. Correlations between variables was analyzed in PASW SPSS and overall survival curves were plotted in Graph Pad prism 5. Results: The mean age for them at diagnosis was $51.5{\pm}12.6$ years (range, 22-76 years). Among the 33 patients that were sequenced, 12 samples in the KRAS gene had a nucleotide change, 11 in codon 12 and 1 in codon 13.There was no significant relationship between the mutation and clinical and pathological aspects of the disease. Conclusions: Knowledge of the KRAS status can help in decision-making to treat metastatic colorectal cancer patients more efficiently and increase survival. However, many Kurdish people due to economic problems are not able to do this valuable genetic test. In addition, we need more careful research of KRAS oncogene at the molecular level in young populations with more patients.