• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.1049-1052
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• 2012

The purpose of this study was to evaluate expression and prognostic value of matrix metalloproteinase-7 (MMP-7) in colorectal cancer (CRC) patients. CRC tissues and corresponding distal normal mucosa tissues of 118 CRC patients were assessed by immunohistochemistry. Correlations between MMP-7 expression, patients' clinic pathological features, and overall survival rate were analyzed. We found that positive expression of MMP-7 in CRC tissues was significantly higher than that in distal normal mucosa (61.0% vs. 39.8%, p =0.001). Poor histological differentiation, advanced clinical stage and lymph node metastasis were significantly correlated with MMP-7 expression in CRC. The overall survival rate was significantly higher in the MMP-7 negative group than the positive group (Log-rank test= 9.957, p= 0.002). MMP-7 appeared as a significant independent prognostic factor through multivariate survival analysis. Collectively, we found MMP-7 expression to be correlated with progression and metastasis of CRC and thus could be used as a predictive marker of prognosis in CRC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1767-1770
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• 2012

Background: The Asia Pacific consensus for colorectal cancer (CRC) recommends that screening programs should begin by the age of 50. However, there have been reports about increasing incidence of CRC at a younger age (i.e. early-onset CRC). Little is known about the features of early-onset CRC in the Vietnamese population. Aim: To describe the clinical, endoscopic and pathological characteristics of early-onset CRC in Vietnamese. Method: A prospective, cross-sectional study was conducted at the University Medical Center from March 2009 to March 2011. All patients with definite pathological diagnosis of CRC were recruited. The early-onset CRC group were analyzed in comparison with the late-onset (i.e. ${\geq}$ 50-year-old) CRC group. Results: The rate of early-onset CRC was 28% (112/400) with a male-to-female ratio of 1.3. Some 22.3% (25/112) of the patients only experienced abdominal pain and/or change in bowel habit without alarming symptoms, 42.9% (48/112) considering their symptoms intermittent. The rate of familial history of CRC in early-onset group was significantly higher that of the late-onset group (21.4% versus 7.6%, p<0.001). The distribution of CRC lesions in rectum, distal and proximal colon were 51.8% (58/112), 26.8% (30/112) and 21.4% (24/112), respectively; which was not different from that in the late-onset group (${\chi}2$, p = 0.29). The rates for poorly differentiated tumors were also not significantly different between the two groups: 12.4% (14/112) versus 8.3% (24/288) (${\chi}2$, p = 0.25). Conclusion: A high proportion of CRC in Viet Nam appear at an earlier age than that recommended for screening by the Asia Pacific consensus. Family history was a risk factor of early-onset CRC. Diagnosis of early-onset CRC needs more attention because of the lack of alarming symptoms and their intermittent patterns as described by the patients.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2051-2055
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• 2012

Background: The cell cycle checkpoint kinase 2 (CHEK2) gene I157T variant may be associated with an increased risk of colorectal cancer, but it is unclear whether the evidence is sufficient to recommend testing for the mutation in clinical practice. Materials and Methods: We systematically searched PubMed, EMBASES, Elsevier and Springer for relevant articles before Apr 2012. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using a fixed-effects or random-effects models with Review Manager 5.0 software. Results: A total of seven studies including 4,029 cases and 13,844 controls based on the search criteria were included for analysis. A significant association of the CHEK2 I157T C variant with unselected CRC was found (OR = 1.61, 95% CI = 1.40-1.87, P < 0.001). We also found a significant association with sporadic CRC (OR = 1.48, 95% CI = 1.23-1.77, P < 0.001) and separately with familial CRC (OR = 1.97, 95% CI = 1.41-2.74, P < 0.001). Conclusion: This meta-analysis demonstrates that the CHEK2 I157T variant may be another important CRC-predisposing gene, which increases CRC risk, especially in familial CRC.

• Biomolecules & Therapeutics
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• v.31 no.6
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• pp.655-660
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• 2023

Colorectal cancer (CRC) is one of the most high-risk cancers; however, it has been suggested that estrogen signaling in CRC could have a protective effect. Therefore, we focused on the function of the G protein-coupled estrogen receptor (GPER) among the estrogen receptors in CRC. In this study, we investigated the therapeutic effect of resveratrol via GPER in CRC (RKO and WiDr) cells, CRC cell-derived xenograft models, and organoids (30T and 33T). Resveratrol significantly suppressed cell viability and proliferation in highly GPER-expressing RKO cells compared to that in low GPER-expressing WiDr cells. In xenograft models, resveratrol also delayed tumor growth and exhibited a high survival rate depending on GPER expression in RKO-derived tumors. Furthermore, resveratrol significantly inhibited the viability of organoids with high GPER expression. Additionally, the anticancer effect of resveratrol on CRC showed that resveratrol rapidly responded to GPER, while increasing the expression of p-ERK and Bax and cleaving PARP proteins.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.397-405
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• 2014

Obesity has been considered as an important risk factor for the development of colorectal cancer (CRC), but the association has not been fully elucidated. Obesity is linked significantly to adipose tissue dysfunction and to alteration of adipokines in blood; in particular, obesity-induced inflammation is thought to be an important link between obesity and colorectal cancer. Based on epidemiological studies, we undertook a systematic review to understand the association of circulating levels of selected adipokines, including adiponectin, leptin, resistin, IL-6 and TNF-${\alpha}$, with the level of CRC risk. Most prospective studies suggested protective effects of adiponectin, but these were attenuated by body mass index (BMI) and waist circumference (WC) data in our meta-analysis. On the other hand, meta-analyses for leptin and CRC did not demonstrate any association, similar to the results of systematic review. Although it proved difficult to determine whether other selected adipokines (resistin, IL-6 and TNF-${\alpha}$) were related to CRC risk due to small number of reports, the present systematic review suggested a positive association with elevated resistin levels but null associations with IL-6 and TNF-${\alpha}$.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2055-2060
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• 2016

Background: Colorectal cancer (CRC) is one of the most common causes of death worldwide and in Thailand. The X-ray repair cross-complementary protein 1 (XRCC1) is required for efficient DNA repair. The effects of this gene on survival in colorectal cancer remain controversial and have not been reported in Thailand. The aim of this study was to investigate the association of the XRCC1 gene with survival of colorectal cancer patients in a Thai population. Materials and Methods: Data and blood samples were collected from 255 newly diagnosed and pathologically confirmed CRC patients who were recruited during the period 2002 to 2006 and whose vital status was followed up until 31 October, 2014. Real-time PCR-HRM was used for genotype identification. The Kaplan-Meier method, the log-rank test, and Cox proportional hazard regression were used to estimate cumulative survival curves and compare various survival distributions and adjusted hazard ratios. Results: Most of the cases were males, and the median age was 55 years. The median survival time was 2.43 years. The cumulative 1-, 3-, 5-, 7-, and 10 year survival rates were 76.70%, 39.25%, 26.50%, 16.60% and 3.56%, respectively. After adjustment, female gender, ages 50-59 and ${\geq}60years$, tumour stage III+IV, a signet-ring cell carcinoma, and poor differentiation had significant associations with increased risk of CRC death. While the XRCC1 Arg/Arg homozygote appeared to be a risk factor for CRC death, the association was not significant. Conclusions: The genetic variant in the XRCC1 may not be associated with the survival of CRC patients in Thailand. Further studies are needed to verify our findings.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7981-7984
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• 2014

Purpose: Colorectal cancer (CRC) screening with fecal occult blood testing (FOBT) has been associated with a reduction in CRC incidence and CRC-related mortality. However, a conventional FOBT requires stool collection and handling, which may be inconvenient for participants. The EZ-Detect$^{TM}$ (Siam Pharmaceutical Thailand) is a FDA-approved chromogen-substrate based FOBT which is basically a self-checked FOBT (no stool handling required). This study aimed to evaluate the accuracy of EZ-Detect for CRC detection. Methods: This prospective study was conducted in the Faculty of Medicine, Siriraj Hospital, Bangkok, Thailand between November 2013 and May 2014. Some 96 patients with histologically-proven CRC and 101 patients with normal colonoscopic findings were invited to perform self-checked FOBT according to the manufacturer's instructions. Results were compared with endoscopic and pathologic findings. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for CRC detection were calculated. Results: The present study revealed the sensitivity, specificity, PPV and NPV of this self-checked FOBT for CRC detection to be 41% (95% CI: 31-51), 97% (95% CI: 92-99), 93% (95% CI: 81-98) and 63% (95% CI: 55-70), respectively. The overall accuracy of the self-checked FOBT for identifying CRC was 70%. The sensitivity for CRC detection based on 7th AJCC staging was 29% for stage I, 32% for stage II and 50% for stage III/IV (P=0.19). The sensitivity was 33% for proximal colon and 42% for distal colon and rectal cancer (P=0.76). Notably, none of nine infiltrative lesions gave a positive FOBT. Conclusions: The self-checked FOBT had an acceptable accuracy of CRC detection except for infiltrative tumors. This home-administrated or 'DIY' do-it-yourself FOBT could be considered as one non-invasive and convenient tool for CRC screening.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1945-1952
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• 2015

Inflammatory bowel disease (IBD) is a disease strongly associated with colorectal cancer (CRC) as a well-known precancerous condition. Alterations in DNA methylation and mutation in K-ras are believed to play an early etiopathogenic role in CRC and may also an initiating event through deregulation of molecular signaling. Epigenetic silencing of APC and SFRP2 in the WNT signaling pathway may also be involved in IBD-CRC. The role of aberrant DNA methylation in precancerous state of colorectal cancer (CRC) is under intensive investigation worldwide. The aim of this study was to investigate the status of promoter methylation of MGMT-B, APC1A and SFRP2 genes, in inflamed and normal colon tissues of patients with IBD compared with control normal tissues. A total of 52 IBD tissues as well as corresponding normal tissues and 30 samples from healthy participants were obtained. We determined promoter methylation status of MGMT-B, SFRP2 and APC1A genes by chemical treatment with sodium bisulfite and subsequent MSP. The most frequently methylated locus was MGMT-B (71%; 34 of 48), followed by SFRP2 (66.6 %; 32 of 48), and APC1A (43.7%; 21 of 48). Our study demonstrated for the first time that hypermethylation of the MGMT-B and the SFRP2 gene promoter regions might be involved in IBD development. Methylation of MGMT-B and SFRP2 in IBD patients may provide a method for early detection of IBD-associated neoplasia.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5037-5041
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• 2013

Accumulated evidence has indicated that Ephrin A1 (EFNA1) is associated with angiogenesis and tumorigenesis in various types of malignancies, including colorectal cancer (CRC). In the current study, we performed an online search using the public microarray database to investigate whether EFNA1 expression might be altered in CRC tissues. We then conducted a case-control study including 306 subjects (102 cases and 204 well-matched controls) in Xiaoshan County to assess any association between genetic polymorphisms in EFNA1 and CRC susceptibility. Searches in the Oncomine expression profiling database revealed EFNA1 to be overexpressed in CRC tissue compared with adjacent normal tissue. The rs12904 G-A variant located in the 3' untranslated region (UTR) of EFNA1 was observed to be associated with CRC susceptibility. Compared with the AA homozygous genotype, those carrying GA genotype had a decreased risk of developing CRC (odds ratio (OR)=0.469, 95% confidence interval (CI): 0.225-0.977, and P=0.043). The association was stronger among smokers and tea drinkers, however, no statistical evidence of interaction between rs12904 polymorphism and smoking or tea drinking on CRC risk was found. Our results suggest that EFNA1 is involved in colorectal tumorigenesis, and rs12904 A>G polymorphism in the 3' UTR of EFNA1 is associated with CRC susceptibility. Larger studies and further mechanistic investigations are warranted to confirm our findings.

• BMB Reports
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• v.51 no.11
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• pp.563-571
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• 2018

Colorectal cancer (CRC), the third most common cancer in the world, has no specific biomarkers that facilitate its diagnosis and subsequent treatment. The miRNAs, small single-stranded RNAs that repress the mRNA translation and trigger the mRNA degradation, show aberrant levels in the CRC, by which these molecules have been related with the initiation, progression, and drug-resistance of this cancer type. Numerous studies show the microRNAs influence the cellular mechanisms related to the cell cycle, differentiation, apoptosis, and migration of the cancer cells through the post-transcriptionally regulated gene expression. Specific patterns of the upregulated and down-regulated miRNA have been associated with the CRC diagnosis, prognosis, and therapeutic response. Concretely, the downregulated miRNAs represent attractive candidates, not only for the CRC diagnosis, but for the targeted therapies via the tumor-suppressing microRNA replacement. This review shows a general overview of the potential uses of the miRNAs in the CRC diagnosis, prognosis, and treatment with a special focus on the downregulated ones.