• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.8
• /
• pp.4025-4030
• /
• 2016

Background: Correlation between colorectal cancer (CRC) and abdominal obesity has been established, but there is a paucity of data on non-obese CRC patients. The aim of this study was to establish the characteristics of CRCs that occur in such patients. Materials and Methods: Consecutive CRC patients without cachexia were included. Unintended body weight loss, T4- or M1-staged CRCs, extensive lymph node involvement, or synchronous malignancy were classified as cachectic conditions. Abdominal fat volumes were measured using a multidetector CT unit with a software (Rapidia, INFINITT, Seoul, Korea). Results: Of the newly-diagnosed CRC patients, 258 non-cachectic and 88 cachectic patients were analyzed. The cancer size (p<0.001) and T stage (p<0.001) were inversely correlated with body mass index (BMI), visceral fat and subcutaneous fat volumes. Cancer size was the only independent factor related to BMI (p=0.016), visceral fat volume (p=0.002), and subcutaneous fat volume (p=0.027). In non-cachectic patients, a significant inverse correlation was found only between the cancer size and visceral fat volume (p=0.017). Conclusions: Non-obese CRC patients tend to have larger CRC lesions than their obese counterparts even under non-cachectic conditions. Such an inverse correlation between cancer size and visceral fat volume suggests that considerable CRCs are not correlated with abdominal obesity.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.18
• /
• pp.8053-8058
• /
• 2016

Metformin is known as a hypoglycaemic agent that regulates glucose homeostasis by inhibiting liver glucose production and increasing muscle glucose uptake. Colorectal cancer (CRC) is one of the most common cancers worldwide, with about a million new cases diagnosed each year. The risk factors for CRC include advanced age, smoking, black race, obesity, low fibre diet, insulin resistance, and the metabolic syndrome. We have searched Medline for the metabolic syndrome and its relation to CRC, and metformin as a potential treatment of colorectal cancer. Administration of metformin alone or in combination with chemotherapy has been shown to suppress CRC. The mechanism that explains how insulin resistance is associated with CRC is complex and not fully understood. In this review we have summarised studies which showed an association with the metabolic syndrome as well as studies which tackled metformin as a potential treatment of CRC. In addition, we have also provided a summary of how metformin at the cellular level can induce changes that suppress the activity of cancer cells.

• Journal of Preventive Medicine and Public Health
• /
• v.51 no.6
• /
• pp.281-288
• /
• 2018

Objectives: We investigated the association between cholecystectomy or appendectomy and the subsequent risk of colorectal cancer (CRC) in the Korean population. Methods: A retrospective cohort study was conducted with the National Health Insurance Service-National Sample Cohort of Korea; this sample was followed up from January 1, 2002, until the date of CRC incidence, loss to follow-up, or December 31, 2015. The exposure status of cholecystectomy and appendectomy was treated as a time-varying covariate. The calculated risk of CRC was stratified by follow-up period, and the association between these surgical procedures and CRC was investigated by a Cox regression model applying appropriate lag periods. Results: A total of 707 663 individuals were identified for analysis. The study population was followed up for an average of 13.66 years, and 4324 CRC cases were identified. The hazard ratio (HR) of CRC was elevated in the first year after cholecystectomy (HR, 1.71; 95% confidence interval [CI], 1.01 to 2.89) and in the first year and 2-3 years after appendectomy (HR, 4.22; 95% CI, 2.87 to 6.20; HR, 2.34; 95% CI, 1.36 to 4.03, respectively). The HRs of CRC after applying 1 year of lag after cholecystectomy and 3 years of lag after appendectomy were 0.80 (95% CI, 0.57 to 1.13) and 0.77 (95% CI, 0.51 to 1.16), respectively. Conclusions: The risk of CRC increased in the first year after cholecystectomy and appendectomy, implying the possibility of bias. When appropriate lag periods after surgery were applied, no association was found between cholecystectomy or appendectomy and CRC.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.9
• /
• pp.4453-4458
• /
• 2012

Angiogenesis plays a significant role in colorectal cancer (CRC) and cyclooxygenase-2 (COX-2) appears to be involved with multiple aspects of CRC angiogenesis. Our aim was to investigate the inhibitory effects of Tan II-A (Tanshinone II-A, Tan II-A) on tumor growth in mice, as well as alteration of expression of COX-2 and VEGF in CRC. We established the mice xenograft model of C26 CRC cell line, and injected 0.5, 1, 2mg/kg of Tan II-A and 1mg/kg of 5-FU in respectively in vivo. Then, we assayed tumor weight and volume, and evaluated microvascular density and expression of VEGF. COX-2 promoter and COX-2 plasmids were transfected into HCT-116 cells, followed by detection of COX-2 promoter activity by chemiluminescence, and detection of COX-2 mRNA expression by fluorescence quantitative PCR. Taken together, the results showed Tan II-A could inhibit tumor growth and suppress the VEGF level in vivo. HCT-116 cell experiments showed marked inhibitory effects of Tan II-A on COX-2 and VEGF in a dose-dependent manner. The results indicate that Tan II-A can effectively inhibit tumor growth and angiogenesis of human colorectal cancer via inhibiting the expression level of COX-2 and VEGF.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.11
• /
• pp.6487-6491
• /
• 2013

To investigate the cognition of medical professionals when following screening guidelines for colorectal cancer (CRC) and barriers to CRC screening. Between February 2012 and December 2012, an anonymous survey with 19-questions based on several CRC screening guidelines was randomly administered to gastroenterologists, oncologists, general surgeons, and general practitioners in Jiangsu, a developed area in China where the incidence of CRC is relatively high. The average cognitive score was 26.4% among 924 respondents. Gastroenterologists and oncologists had higher scores compared with others (p<0.01 and p<0.01, respectively); doctor of medicine (M.D.) with or without doctor of philosophy (Ph.D.) or holders with bachelor of medical science (BMS) achieved higher scores than other lower degree holders (P<0.05). More importantly, doctors who finished CRC related education in the past year achieved higher scores than the others (p<0.001). The most commonly listed barriers to referring high-risk patients for CRC screening were "anxiety about colonoscopy without anesthesia", "lack of awareness of the current guidelines" and "lack of insurance reimbursement". Lack of cognition was detected among doctors when following CRC screening guidelines for high-risk populations. Educational programs should be recommended to improve their cognition and reduce barriers to CRC screening.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.7
• /
• pp.3209-3212
• /
• 2012

Introduction: Colorectal carcinoma (CRC) is the most common gastrointestinal malignancy in the older population, but it is also quite frequent among young adults in developing countries. The aim of this study was to update the trends of clinicopathological features of CRC in young Nepalese. Methods: A retrospective comparative study on the data retrieved from the surgical records of all patients between 20 to 39 years of age with CRC was carried out for periods of 5 years each from 1999 to 2003 (early) and 2004 to 2008 (recent), treated at Tribhuvan University Teaching Hospital, Kathmandu, Nepal. Results: The number of young adults with CRC increased from 28 to 34. However, the proportion of young patients in both groups was 28% of all CRC patients. The mean ages were $34{\pm}4.7$ and $31.8{\pm}5.1$ years in early and recent 5 years, respectively, and the male female ratio changed from 2:3 to 4:3. Abdominal pain as the most common presenting symptom was replaced by bleeding per rectum in recent years. The mean duration from onset of symptoms to seeking medical advice decreased from 7.8 months to 5.6 months in recent years. More patients (85.3%) were subjected to endoscopic examination in recent years than early years (60.7%) and right colonic cancer increased from 10.7% to 26.5%. However, the rectum was the commonest site in both early (71.4%) and recent (50%) groups. CRC was detected significantly at an earlier stage (7.1% vs 32.4%) in recent years with large proportion of modified Dukes B stage. Poorly differentiated adenocarcinoma was the predominant histology in both groups (50% vs 60.7%). Curative resection had risen in recent years (39.3% vs 73.6%). Conclusion: CRC among Nepalese young adults accounts for a high incidence (28%) of all CRC cases. Although right sided colonic cancer has been increasing, rectum is the commonest site. There is also an increasing trend for diagnosis at earlier stages of the disease which can be treated with curative intent.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.8
• /
• pp.3667-3673
• /
• 2014

Background: colorectal cancer (CRC) is the third most common type of cancers and the fourth leading cause of death worldwide. In Saudi Arabia, CRC accounts for 8.5% of all tumors; it ranks first among all cancers in males and third among females. The aim of this study was to link between different PARP-1 mutations and risk of CRC in Saudi population and to determine common variants of PARP-1 in Saudi CRC patients and normal individuals. Materials and Methods: DNA samples were isolated from fifty CRC patients and from a comparable number of control subjects then sequenced to detect different variations present in exons 3, 17, and 21 of the PARP-1 gene. Results and Conclusions: When comparing the genotype and allele frequencies of all detected SNPs in CRC patients with those in controls, we found none were significantly different for all variants even the most common SNP in PARP-1 gene (Val762Ala). However, two novel alterations in exon 21 were found to be associated with increased risk of CRC. The variants identified as (1) Lys933Asn [p-value 0.0318] and (2) Lys945Asn [p-value 0.0257]. Our results suggest that PARP-1 Lys933Asn and Lys945Asn alterations could be associated with increased risk of CRC in the Saudi population.

• Journal of Cancer Prevention
• /
• v.23 no.4
• /
• pp.183-190
• /
• 2018

Background: As the number of big-cohort studies increases, validation becomes increasingly more important. We aimed to validate administrative database categorized as colorectal cancer (CRC) by the International Classification of Disease (ICD) 10th code. Methods: Big-cohort was collected from Clinical Data Warehouse using ICD 10th codes from May 1, 2003 to November 30, 2016 at Seoul National University Bundang Hospital. The patients in the study group had been diagnosed with cancer and were recorded in the ICD 10th code of CRC by the National Health Insurance Service. Subjects with codes of inflammatory bowel disease or tuberculosis colitis were selected for the control group. For the accuracy of registered CRC codes (C18-21), the chart, imaging results, and pathologic findings were examined by two reviewers. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for CRC were calculated. Results: A total of 6,780 subjects with CRC and 1,899 control subjects were enrolled. Of these patients, 22 subjects did not have evidence of CRC by colonoscopy, computed tomography, magnetic resonance imaging, or positron emission tomography. The sensitivity and specificity of hospitalization data for identifying CRC were 100.00% and 98.86%, respectively. PPV and NPV were 99.68% and 100.00%, respectively. Conclusions: The big-cohort database using the ICD 10th code for CRC appears to be accurate.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.8
• /
• pp.3279-3283
• /
• 2015

Background: Colorectal cancer (CRC) is the most common gastrointestinal cancer and the incidence is increasing. CRC is more common with increasing age, but a proportion occurs in young adults, termed young CRC. This study assessed the incidence and the demographic of young CRC in Brunei Darussalam. Materials and Methods: All histologically proven CRC between 1986 and 2014 registered with the Department of Pathology cancer registry were reviewed and data extracted for analyses. Young CRC was defined as cancer in patients aged less than 45 years. The various population groups were categorized into locals (Malays, Chinese and Indigenous) and expatriates. Results: Over the study period, there were 1,126 histologically proven CRC (mean age $59.1{\pm}14.7$ years, Male 58.0%, Locals 91.8% and 8.2% expatriates). Young CRC accounted for 15.1% with the proportion declining over the years, from 29% (1986-1990) to 13.2% (2011-2014). The proportion of young CRC was highest among the indigenous (30.8%), followed by the expatriates (29.3%), Malays (14.3%) and lowest among the Chinese (10.8%). The mean age of young CRC was $35.9{\pm}6.2$; lowest among the indigenous ($33.5{\pm}6.7$), expatriate ($34.9{\pm}6.0$) groupd and the Malays ($35.6{\pm}6.5$) compared to the Chinese ($38.6{\pm}4.6$), a similar trend being observed in the non-young CRC groups. There were no difference between the genders and tumor locations (rectum or colon) between the young and the non-young CRC cases. Female young CRC was significantly younger than male (p<0.05) without any significant variation between the various population groups (p>0.05). Conclusions: Our study showed that the young CRC accounted for 15.1% of all CRC with declining trend observed over recent years. Young CRC was more common among indigenous, expatriates and Malays and least common among the Chinese. There were no differences in the gender and tumor locations.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.6
• /
• pp.2397-2402
• /
• 2015

Previous studies have shown that miR-454 plays an important role in a variety of biological processes in various human cancer cells. However, the underlying mechanisms of this microRNA in colorectal cancer (CRC) cells remain largely unknown. In the present study, we investigated the miR-454 role in CRC cell proliferation. We found that miR-454 expression is markedly upregulated in CRC tissues and CRC cells compared with the matched tumor adjacent tissues and the FHC normal colonic cell line. Ectopic expression of miR-454 promoted the proliferation and anchorage-independent growth of CRC cells, whereas inhibition of miR-454 reduced this effect. Bioinformatics analysis further revealed cylindromatosis (CYLD), a putative tumor suppressor as a potential target of miR-454. Data from luciferase reporter assays showed that miR-454 directly binds to the 3'-untranslated region (3'-UTR) of CYLD mRNA and repressed expression at both transcriptional and translational levels. In functional assays, CYLD-silenced in miR-454-in-transfected SW480 cells have positive effect to promote cell proliferation, suggesting that direct CYLD downregulation is required for miR-454-induced CRC cell proliferation. In sum, our data provide compelling evidence that miR-454 functions as an onco-miRNA, playing a crucial role in the promoting cell proliferation in CRC, and its oncogenic effect is mediated chiefly through direct suppression of CYLD expression.