• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1663-1666
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• 2012

Background and Objective: Protein expression in colon and rectal cancer (CRC) and paired normal tissues was examined by two-dimensional gel electrophoresis (2-DE) to identify differentially expressed proteins. Materials and Methods: Five fresh colorectal cancer and paired adjacent normal tissues were obtained and differentially expressed protein spots were determined using PDQuest software, with identification on the basis of MALDI-TOF mass spectra. Results: Compared with normal colorectal mucosa, protein abnormal expression of 65 spots varying more than 1.5 times were found in 2-DE gels from colorectal cancer samples (P<0.05); forty-two proteins were up-regulated and 23 were down-regulated; twelve protein spots were identified using mass spectrometry, of which 8 were up-regulated, includimng HSPB1and Annexin A4, while 4 were down-regulated, the results being consistent with Western blot findings. Conclusions: Two-dimensional electrophoresis reference maps for CRC tissues and adjacent normal mucosa (NMC) were established and 12 differentially expressed proteins were identified. Up-regulated HSPB1 and Annexin A4 may play many important roles in the pathogenesis of colorectal cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권11호
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• pp.4589-4594
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• 2014

The mammalian target of rapamycin (mTOR) signaling pathway is upregulated in the pathogenesis of many cancers, including colorectal cancer (CRC). DEPTOR is an mTOR inhibitor whose expression is negatively regulated by mTOR. However, the role of DEPTOR in the development of CRC is not known. The aim of this study was to investigate the expression of DEPTOR and mTORC1 activity (P-S6) in a subset of CRC patients and determine their relation to tumor differentiation, invasion, nodal metastasis and disease-free survival. Here, Immunohistochemical expression of P-S6 (S235/236) and DEPTOR were evaluated in 1.5 mm tumor cores from 90 CRC patients and in 90 samples of adjacent normal mucosa by tissue microarray. The expression of P-S6 (S235/236) was upregulated in CRC, with the positive rate of P-S6 (S235/236) in CRC (63.3%) significantly higher than that in control tissues (36.7%, 30%) (p<0.05). P-S6 (S235/236) also correlated with high tumor histologic grade (p=0.002), and positive nodal metastasis (p=0.002). In contrast, the expression level of DEPTOR was correlated with low tumor histological grade (p=0.006), and negative nodal metastasis (p=0.001). Interestingly, P-S6 (S235/236) expression showed a significant negative association with the expression of DEPTOR in CRC (p=0.011, R= -0.279). However, upregulation of P-S6 (S235/236) (p=0.693) and downregulation of DEPTOR (p=0.331) in CRC were not significantly associated with overall survival. Thus, we conclude that expression of DEPTOR negatively correlates with mTORC1 activity and tumor progression in CRC. DEPTOR is a potential marker for prognostic evaluation and a target for the treatment of CRC.

• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8093-8100
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• 2016

Background: Genetic and environmental factors play important roles in pathogenesis of digestive tract cancers like those in the esophagus, stomach and colorectum. Folate deficiency and methylenetetrahydrofolate reductase (MTHFR) as an important enzyme of folate and methionine metabolism are considered crucial for DNA synthesis and methylation. MTHFR variants may cause genomic hypomethylation, which may lead to the development of cancer, and MTHFR gene polymorphisms (especially C677T and A1298C) are known to influence predispositions for cancer development. Several case control association studies of MTHFR C677T polymorphisms and colorectal cancer (CRC) have been reported in different populations with contrasting results, possibly reflecting inadequate statistical power. Aim: The present meta-analysis was conducted to investigate the association between the C677T polymorphism and the risk of colorectal cancer. Materials and Methods: A literature search of the PubMed, Google Scholar, Springer link and Elsevier databases was carried out for potential relevant articles. Pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was calculated to assess the association of MTHFR C677T with the susceptibility to CRC. Cochran's Q statistic and the inconsistency index (I2) were used to check study heterogeneity. Egger's test and funnel plots were applied to assess publication bias. All statistical analyses were conducted by with MetaAnalyst and MIX version 1.7. Results: Thirty four case-control studies involving a total of 9,143 cases and 11,357 controls were retrieved according to the inclusion criteria. Overall, no significant association was found between the MTHFR C677T polymorphism and colorectal cancer in Asian populations (for T vs. C: OR=1.03; 95% CI= 0.92-1.5; p= 0.64; for TT vs CC: OR=0.88; 95%CI= 0.74-1.04; p= 0.04; for CT vs. CC: OR = 1.02; 95%CI= 0.93-1.12; p=0.59; for TT+ CT vs. CC: OR=1.07; 95%CI= 0.94-1.22; p=0.87). Conclusions: Evidence from the current meta-analysis indicated that the C677T polymorphism is not associated with CRC risk in Asian populations. Further investigations are needed to offer better insight into any role of this polymorphism in colorectal carcinogenesis.

• 대한의생명과학회지
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• 제27권4호
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• pp.216-222
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• 2021

Colorectal cancer (CRC) is major cancer with high incidence and mortality worldwide. It is known that most CRCs arise from precursor adenomatous polyps (APs). Recently, microRNA (miRNA) has been proposed as a biomarker for various cancers including CRC. In this study, the expression patterns of miR-29a in the whole blood (WB) of CRC, AP, and control groups were analyzed by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) to evaluate the expression level of miR-29a in patients with colorectal neoplasm (CRN) including CRC and AP. As a result, the relative expression of miR-29a was significantly decreased in the patients with CRN compared to the control group (P<0.001). The results were in agreement with previous in vitro cell studies and studies that used tissue and feces samples, suggesting that miR-29a in WB may be useful in demonstrating the status of colorectal tissue. Additionally, we divided the control group into healthy control (HC) without any colorectal symptoms and non-tumor control (NTC) with colorectal symptoms but without any CRN. And then the relative expression of miR-29a was also significantly decreased in the NTC group compared to the HC group (P<0.001). Therefore, our study revealed that miR-29a can differentiate patients with CRN from HC group, but they are also involved in the early stage of inflammatory response and cannot be specific biomarkers for CRN.

• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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• pp.2269-2276
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• 2015

Colorectal cancer (CRC) is now common in Thailand with an increase in incidence over time. Health authorities are planning to implement a nationwide CRC screening program using fecal immunochemical test (FIT) as a primary screening tool. This study aimed to estimate preferences and acceptance of FIT and colonoscopy, explore factors influencing the acceptance, and investigate reasons behind choosing and rejecting to screen before the program was implemented. Patients aged 50-69, visiting the primary care unit during the study period, were invited to join this study. Patients with a history of cancer or past CRC screening were excluded. Face-to-face interviews were conducted. Subjects were informed about CRC and the screening tests: FIT and colonoscopy. Then, they were asked for their opinions regarding the screening. The total number of subjects was 437 (86.7% response rate). Fifty-eight percent were females. The median age was 58 years. FIT was accepted by 74.1% of subjects compared to 55.6% for colonoscopy. The acceptance of colonoscopy was associated with perceived susceptibility to CRC and family history of cancer. No symptoms, unwilling to screen, healthy, too busy and anxious about diagnosis were reasons for refusing to screen. FIT was preferred for its simplicity and non-invasiveness compared with colonoscopy. Those rejecting FIT expressed a strong preference for colonoscopy. Subjects chose colonoscopy because of its accuracy; it was refused for the process and complications. If the screening program is implemented for the entire target population in Thailand, we estimate that 106,546 will have a positive FIT, between 8,618 and 12,749 identified with advanced adenoma and between 2,645 and 3,912 identified with CRC in the first round of the program.

• Asian Pacific Journal of Cancer Prevention
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• 제17권5호
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• pp.2479-2483
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• 2016

Background: This study explored the knowledge and awareness about colorectal cancer (CRC) among undergraduate students of one of the leading universities in Saudi Arabia, along with the mode of information access. Materials and Methods: The present cross-sectional study was conducted at the King Abdulaziz University, Jeddah, Saudi Arabia, among students of different faculties. The study questionnaire, containing 28 items, was adapted from surveys identified in the relevant literature. The CRC awareness questionnaire consisted of an awareness section (early CRC signs and symptoms, and risk factors) and a knowledge section. The data were analyzed using the SPSS version 21.0. Results: A total of 525 undergraduate students participated in the study. The majority were females (63.0%) and approximately half (56.8%) were medical students. The majority of the students (82.3%) were aware of CRC, and 68% thought that CRC is a preventable disease. Regarding colorectal cancer screening tests, only one-third of students (33%) had actual knowledge, while the majority of the students (77.0%) thought that there are tests which help in early detection. Only 4% of the participants had a family history of CRC. The majority of the participants (84%) thought that CRC is a disease that can be cured. Almost 50-60% participants had good awareness level regarding risk factors, and signs and symptoms. Regarding knowledge, participant responses varied for family history (52%), age (59%), chronic infection of the colon (72%), obesity and lack of exercise (66%). More than one-third of the students had received information material regarding CRC from their curriculum followed by social media (20.4%), and nearly 40% from other sources such as TV, hospital and mass media. Female participants had significantly better awareness in a few questions regarding CRC awareness as compared to their male counterparts. There was a significant difference observed between medical and non-medical students (p<0.001) in overall score of awareness and knowledge about CRC while no significant difference found in gender-wise comparison. Conclusions: Knowledge and awareness of students about CRC were not up to the mark. Medical students and female students had better knowledge in a few areas, but the overall situation is dismal.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.619-624
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• 2013

Background: Colorectal cancer (CRC) exists in a more common sporadic form and less common hereditary forms, associated with the Lynch syndrome, familial adenomatous polyposis (FAP) and other rare syndromes. Sporadic CRC is believed to arise as a result of close interaction between environmental factors, including dietary and lifestyle habits, and genetic predisposition factors. In contrast, hereditary forms such as those related to the Lynch syndrome result from inheritance of germline mutations of mismatch repair (MMR) genes. However, in certain cases, the influence of low penetrance alleles in familial colorectal cancer susceptibility is also undeniable. Aim: To investigate the genotype frequencies of MLH1 promoter polymorphism -93G>A and to determine whether it could play any role in modulating familial and sporadic CRC susceptibility risk. Methods: A case-control study comprising of 104 histopathologically confirmed CRC patients as cases (52 sporadic CRC and 52 Lynch syndrome patients) and 104 normal healthy individuals as controls was undertaken. DNA was extracted from peripheral blood and the polymorphism was genotyped employing PCR-RFLP methods. The genotypes were categorized into homozygous wild type, heterozygous and homozygous variants. The risk association between these polymorphisms and CRC susceptibility risk was calculated using binary logistic regression analysis and deriving odds ratios (ORs). Results: When risk association was investigated for all CRC patients as a single group, the heterozygous (G/A) genotype showed a significantly higher risk for CRC susceptibility with an OR of 2.273, (95%CI: 1.133-4.558 and p-value=0.021). When analyzed specifically for the 2 types of CRC, the heterozygous (G/A) genotype showed significantly higher risk for sporadic CRC susceptibility with and OR of 3.714, (95%CI: 1.416-9.740 and p-value=0.008). Despite high OR value was observed for Lynch syndrome (OR: 1.600, 95%CI: 0.715-3.581), the risk was not statistically significant (P=0.253). Conclusion: Our results suggest an influence of MLH1 promoter polymorphism -93G>A in modulating susceptibility risk in Malaysian CRC patients, especially those with sporadic disease.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.5063-5067
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• 2015

Background: Colorectal cancer (CRC) is the most common gastrointestinal malignancy and is a significant cause of mortality. Its incidence is generally increasing in Asia. Reports from the West have indicated that the incidence of rectal cancer is increasing in the younger population. This study assessed the time trend of CRC in Brunei Darussalam specifically assessing the different age groups at which the incidences start to increase. Materials and Methods: The National Cancer registry was reviewed (1991 to 2014). The age standardized rate (ASR) and the age specific incidence rates (ASIRs) for three time periods (1991-1998), (1999-2006) and (2007-2014) were calculated. Results: The mean age of diagnosis was $59.3{\pm}14.6$ years old, incidences being slightly higher amongst men (57.6%) and Malays (67.1%). The most common tumor type was adenocarcinoma (96.4%). Rectal cancers accounted for 35.2% (n=372/1,056) of all cancers of the large bowel; more men were affected than women. The proportion of rectal cancer was also high among the indigenous group. In the three time periods, the ASR for CRC increased from 16 per 100,000 (1991-1998) to 19.6 per 100,000 (1999-2006) and 24.3 per 100,000 (2007-2014). The ASIRs for CRC increased markedly between the time periods 1998-2006 and 2007-2014, beginning in the 40-44 years age group. For rectal cancers, the ASIRs started to increase in the 25-29 age group onward whereas for colon cancers, the increase was observed at a later age, starting from the 45-49 age group. Conclusions: Our study showed an increase in the incidence of CRC including in the younger age groups. The increase was seen earlier in rectal cancer compared to colon cancer. These data mirror the trends reported from the West.

• BMB Reports
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• 제48권6호
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• pp.360-366
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• 2015

Colorectal cancer (CRC), the third most common cancer worldwide, also has the highest rate of cancer-related morbidity and mortality. WNT signaling is initiated by binding of WNT to various receptors, including frizzleds (FZDs), and plays a critical role in CRC and other tumor development by regulating proliferation, differentiation, migration, apoptosis, and polarity. Among the members of the FZD family, FZD6 is broadly expressed in various tissues, and its overexpression has been reported in several cancers, suggesting an important role in cancer development. In this study, we investigated the expression of FZD6 in patients with CRC and found it to be increased in tumors, as compared to paired adjacent non-tumor tissues. Additionally, we found that FZD6 expression was negatively regulated by miR199a5p in CRC cells. These results suggest that overexpression of FZD6, mediated by reduced expression of miR-199a-5p, may play an important role in the development of CRC. [BMB Reports 2015; 48(6): 360-366]

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.1857-1862
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• 2012

To assess the impact of household income and economic recession on participation in CRC screening, we estimated annual participating proportions from 2007 to 2009 for different CRC screening modalities according to household income levels. A total of 8,042 subjects were derived from the fourth Korean National Health and Nutrition Examination Survey (KNHANES IV). Multivariate logistic regression analysis was used to estimate odds ratios and 95% confidence intervals for CRC screening with household income quartiles by gender in each year. People were less likely to attend a high-cost CRC screening such as a sigmoidoscopy or colonoscopy independent of the income quartile during the economic recession. Income disparities for participating in opportunistic cancer screening appear to have existed among both males and females during the three years (2007-2009), but were most distinctive in 2009. An increase in mortality of CRC can therefore be expected due to late detection in periods of economic crisis. Accordingly, the government should expand the coverage of CRC screening to prevent excess deaths by reducing related direct and indirect costs during the economic recession.