• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.551-560
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• 2014

Colorectal cancer (CRC) is the third most common malignancy and fourth most common cause of cancer mortality worldwide. Untreated chronic inflammation in the intestine ranks among the top three high-risk conditions for colitis-associated colorectal cancer (CAC). Signal Transducer and Activator of Transcription 3 (STAT3) protein is a member of the STAT family of transcription factors often deregulated in CRC. In this review, we try to emphasize the critical role of STAT3 in CAC as well as the crosstalk of STAT3 with inflammatory cytokines, nuclear factor (NF)-${\kappa}B$, PI3K/Akt, Mammalian Target of Rapamycin (mTOR), Notch, $Wnt/{\beta}$-catenin and microRNA (MiR) pathways. STAT3 is considered as a primary drug target to treat CAC in humans and rodents. Also we updated the findings for inhibitors of STAT3 with regard to effects on tumorigenesis. This review will hopefully provide insights on the use of STAT3 as a therapeutic target in CAC.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.603-608
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• 2016

Background: The investigation of mutation patterns in oncogenes potentially can make available a reliable mechanism for management and treatment decisions for patients with colorectal cancer (CRC). This study concerns the rate of KRAS and BRAF genes mutations in Iranian metastatic colorectal cancer (mCRC) patients, as well as associations of genotypes with clinicopathological features. Materials and Methods: A total of 1,000 mCRC specimens collected from 2008 to 2012 that referred to the Mehr Hospital and Partolab center, Tehran, Iran enrolled in this cross sectional study. Using HRM, Dxs Therascreen and Pyrosequencing methods, we analyzed the mutational status of KRAS and BRAF genes in these. Results: KRAS mutations were present in 33.6% cases (n=336). Of KRAS mutation positive cases, 85.1% were in codon 12 and 14.9% were in codon 13. The most frequent mutation at KRAS codon 12 was Gly12Asp; BRAF mutations were not found in any mCRC patients (n=242). In addition, we observed a strong correlation of KRAS mutations with some clinicopathological characteristics. Conclusions: KRAS mutations are frequent in mCRCs while presence of BRAF mutations in these patients is rare. Moreover, associations of KRAS genotypes with non-mucinous adenocarcinoma and depth of invasion (pT3) were remarkable.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9773-9779
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• 2014

Background: Colorectal cancer (CRC) is one of the prime causes of mortality around the globe, with a significantly rising incidence in the Middle East region in recent decades. Since detection of CRC in the early stages is an important issue, and also since to date there are no comprehensive epidemiologic studies depicting the Middle East region with special attention to the average risk group, further investigation is of significant necessity in this regard. Aim: Our aim was to investigate the prevalence of preneoplastic and neoplastic lesions of the colon in an average risk population. Materials and Methods: A total of 1,208 eligible asymptomatic, average- risk adults older than 40 years of age, referred to Firuzgar Hospotal in the years 2008-2012, were enrolled. They underwent colonoscopy screening and all polypoid lesions were removed and examined by an expert gastrointestinal pathologist. The lesions were classified by size, location, numbers and pathologic findings. Size of lesions was measured objectively by endoscopists. Results: The mean age of participants was $56.5{\pm}9.59$ and 51.6% were male. The overall polyp detection rate was 199/1208 (16.5 %), 26 subjects having non-neoplastic polyps, including hyperplastic lesions, and 173/1208 (14.3%) having neoplastic polyps, of which 26 (2.15%) were advanced neoplasms. The prevalence of colorectal neoplasia was more common among the 50-59 age group. Advanced adenoma was more frequent among the 60-69 age group. The majority of adenomas were detected in the distal colon, but a quarter of advanced adenomas were found in the proximal colon; advance age and male gender was associated with the presence of adenoma. Conclusions: It seems that CRC screening among average-risk population might be recommended in countries such as Iran. However, sigmioidoscopy alone would miss many colorectal adenomas. Furthermore, the 50-59 age group could be considered as an appropriate target population for this purpose in Iran.

• Journal of Digestive Cancer Reports
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• v.8 no.1
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• pp.56-60
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• 2020

In recent years, liquid biopsy has received immense attention. Liquid biopsy is a minimally invasive method used for obtaining biological fluids including urine, pleural fluid and, mostly, peripheral blood. Liquid biopsy involves various targets including circulating tumors cells (CTCs), circulating cell-free tumor DNA (ctDNA), and microRNA (miRNA). Colorectal cancer (CRC), like other solid tumors, shed tumor cells into the bloodstream. Analysis of these CTCs, as well as ctDNA is the primary objective of the liquid biopsy. Evaluation of CTC or ctDNA offers information about early tumor release, development of tumor metastasis and also about mechanisms involved in tumor resistance to treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1917-1923
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• 2016

Background: Lynch Syndrome (LS) is a familial cancer condition caused by germline mutations in DNA mismatch repair genes. Individuals with LS have a greatly increased risk of developing colorectal cancer (CRC) and it is therefore important to identify mutation carriers so they can undergo regular surveillance. Tumor DNA from LS patients characteristically shows microsatellite instability (MSI). Our aim here was to screen young CRC patients for MSI as a first step in the identification of unrecognized cases of LS in the Saudi population. Materials and Methods: Archival tumor tissue was obtained from 284 CRC patients treated at 4 institutes in Dammam and Riyadh between 2006 and 2015 and aged less than 60 years at diagnosis. MSI screening was performed using the BAT-26 microsatellite marker and positive cases confirmed using the pentaplex MSI analysis system. Positive cases were screened for BRAF mutations to exclude sporadic CRC and were evaluated for loss of expression of 4 DNA mismatch repair proteins using immunohistochemistry. Results: MSI was found in 33/284 (11.6%) cases, of which only one showed a BRAF mutation. Saudi MSI cases showed similar instability in the BAT-26 and BAT-25 markers to Australian MSI cases, but significantly lower frequencies of instability in 3 other microsatellite markers. Conclusions: MSI screening of young Saudi CRC patients reveals that approximately 1 in 9 are candidates for LS. Patients with MSI are strongly recommended to undergo genetic counselling and germline mutation testing for LS. Other affected family members can then be identified and offered regular surveillance for early detection of LS-associated cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5523-5528
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• 2014

Objective: To evaluate the implementation of screening colonoscopy amongst first-degree relatives (FDRs) of patients with colorectal cancer (CRC) in Turkey. Materials and Methods: A total of 400 first-degree relatives (mean(SD)age: 42.5(12.7) years, 55.5% were male) of 136 CRC patients were included in this cross-sectional questionnaire based survey. Data on demographic characteristics, relationship to patient and family history for malignancy other than the index case were evaluated in the FDRs of patients as were the data on knowledge about and characteristics related to the implementation of screening colonoscopy using a standardized questionnaire form. Results: The mean(SD) age at diagnosis of CRC in the index patients was 60.0(14.0) years, while mean(SD) age of first degree relatives was 42.5(12.7) years. Overall 36.3% of relatives were determined to have knowledge about colonoscopy. Physicians (66.9%) were the major source of information. Screening colonoscopy was recommended to 19.5% (n=78) of patient relatives, while 48.7% (n=38) of individuals participated in colonoscopy procedures, mostly (57.9%) one year after the index diagnosis. Screening colonoscopy revealed normal findings in 25 of 38 (65.8%) cases, while precancerous lesions were detected in 26.3% of screened individuals. In 19.0% of FDRs of patients, there was a detected risk for Lynch syndrome related cancer. Conclusions: In conclusion, our findings revealed that less than 20% of FDRs of patients had received a screening colonoscopy recommendation; only 48.7% participated in the procedure with detection of precancerous lesions in 26.3%. Rise of awareness about screening colonoscopy amongst patients with CRC and first degree relatives of patients and motivation of physicians for targeted screening would improve the participation rate in screening colonoscopy by FDRs of patients with CRC in Turkey.

• BMB Reports
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• v.57 no.3
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• pp.161-166
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• 2024

Aberrant DNA methylation plays a critical role in the development and progression of colorectal cancer (CRC), which has high incidence and mortality rates in Korea. Various CRC-associated methylation markers for cancer diagnosis and prognosis have been developed; however, they have not been validated for Korean patients owing to the lack of comprehensive clinical and methylome data. Here, we obtained reliable methylation profiles for 228 tumor, 103 adjacent normal, and two unmatched normal colon tissues from Korean patients with CRC using an Illumina Infinium EPIC array; the data were corrected for biological and experiment biases. A comparative methylome analysis confirmed the previous findings that hypermethylated positions in the tumor were highly enriched in CpG island and promoter, 5' untranslated, and first exon regions. However, hypomethylated positions were enriched in the open-sea regions considerably distant from CpG islands. After applying a CpG island methylator phenotype (CIMP) to the methylome data of tumor samples to stratify the CRC patients, we consolidated the previously established clinicopathological findings that the tumors with high CIMP signatures were significantly enriched in the right colon. The results showed a higher prevalence of microsatellite instability status and MLH1 methylation in tumors with high CMP signatures than in those with low or non-CIMP signatures. Therefore, our methylome analysis and dataset provide insights into applying CRC-associated methylation markers for Korean patients regarding cancer diagnosis and prognosis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4437-4441
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• 2014

SMAD7 has been identified as a functional candidate gene for colorectal cancer (CRC). SMAD7 protein is a known antagonist of the transforming growth factor beta ($TGF-{\beta}$) signaling pathway which is involved in tumorigenesis. Polymorphisms in SMAD7 may thus alter cancer risk. The aim of this study was to investigate the influence of a SMAD7 gene polymorphism (rs2337107) on risk of CRC and clinicopathological features in an Iranian population. In total, 210 subjects including 105 patients with colorectal cancer and 105 healthy controls were recruited in our study. All samples were genotyped by TaqMan assay via an ABI 7500 Real Time PCR System (Applied Biosystems) with DNA from peripheral blood. The polymorphism was statistically analyzed to investigate the relationship with the risk of colorectal cancer and clinicopathological properties. Logistic regression analysis revealed that there was no significant association between rs2337107and the risk of colorectal cancer. In addition, no significant association between genotypes and clinicopathological features was observed (p value>0.05). Although there was not any association between genotypes and disorder, CT was the most common genotype in this population. This genotype prevalence was also higher in the patients with well grade (54.9%) and colon (72.0%) tumors. Our results provide the first evidence that this polymorphism is not a potential contributor to the risk of colorectal cancer and clinicopathological features in an Iranian population, and suggests the need of a large-scale case-control study to validate our results.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7683-7688
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• 2015

Background: The study evaluated the patient, lifestyle and tumor profile in patients undergoing upfront surgery for sporadic colorectal cancer (CRC) in Indian population. Materials and Methods: One hundred consecutive patients were included. Details related to their demographic profile, habits, signs and symptoms, tumor profile, further treatment and follow up were recorded. Results: The majority of the patients had colonic cancer (68%), advanced tumor stage 3 & 4 (46%), moderately differentiated tumors (70%) with absence of lymphatic invasion (60%) and metastasis (90%). Correlations between tumor location and abdominal pain (p-value 0.002), bleeding per rectum (p-value <0.001), difficulty in micturition (p-value 0.012) and constipation (p-value 0.007) were found to be statistically significant. Abdominal pain was more frequently reported in patients with metastasis (p-value 0.031). Loss of weight statistically correlated with absence of lymphatic invasion (p-value 0.047). Associations between tumor stage and alcohol intake (p-value 0.050) and non vegetarian diet (p-value 0.006); lymphatic invasion and intake of spicy food (p-value 0.040) and non vegetarian diet (p-value 0.001) and metastasis and alcohol intake (p-value 0.041) were also observed. Age and tumor grade were also correlated (p-value 0.020). Conclusions: Minimizing the adverse lifestyle factors can help in reducing the overall incidence of CRC in the Indian population.

• Journal of Preventive Medicine and Public Health
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• v.51 no.1
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• pp.33-40
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• 2018

Objectives: The aim of this study was to determine the factors associated with the spatial distribution of the incidence of colorectal cancer (CRC) in the neighborhoods of Tehran, Iran using Bayesian spatial models. Methods: This ecological study was implemented in Tehran on the neighborhood level. Socioeconomic variables, risk factors, and health costs were extracted from the Equity Assessment Study conducted in Tehran. The data on CRC incidence were extracted from the Iranian population-based cancer registry. The $Besag-York-Molli{\acute{e}}$ (BYM) model was used to identify factors associated with the spatial distribution of CRC incidence. The software programs OpenBUGS version 3.2.3, ArcGIS 10.3, and GeoDa were used for the analysis. Results: The Moran index was statistically significant for all the variables studied (p<0.05). The BYM model showed that having a women head of household (median standardized incidence ratio [SIR], 1.63; 95% confidence interval [CI], 1.06 to 2.53), living in a rental house (median SIR, 0.82; 95% CI, 0.71 to 0.96), not consuming milk daily (median SIR, 0.71; 95% CI, 0.55 to 0.94) and having greater household health expenditures (median SIR, 1.34; 95% CI, 1.06 to 1.68) were associated with a statistically significant elevation in the SIR of CRC. The median (interquartile range) and mean (standard deviation) values of the SIR of CRC, with the inclusion of all the variables studied in the model, were 0.57 (1.01) and 1.05 (1.31), respectively. Conclusions: Inequality was found in the spatial distribution of CRC incidence in Tehran on the neighborhood level. Paying attention to this inequality and the factors associated with it may be useful for resource allocation and developing preventive strategies in at-risk areas.