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Prevention of Colorectal (Bowel) Cancer

Research suggests that having a healthy diet (low-fat, high-fibre, plenty of fresh fruit and vegetables and wholegrains), regular exercise, maintaining a healy weight and not smoking can reduce your risk of bowel cancer and other types of cancer. In people with a high risk of developing bowel cancer (e.g. genetic predisposition) polyp removal and other interventions may be indicated, currently there is research into chemoprevention.

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Latest Research Publications
Screening for Colorectal (Bowel) Cancer

Information Patients and the Public (5 links)

Information for Health Professionals / Researchers (3 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Beets G, Sebag-Montefiore D, Andritsch E, et al.
ECCO Essential Requirements for Quality Cancer Care: Colorectal Cancer. A critical review.
Crit Rev Oncol Hematol. 2017; 110:81-93 [PubMed] Related Publications
BACKGROUND: ECCO essential requirements for quality cancer care (ERQCC) are checklists and explanations of organisation and actions that are necessary to give high-quality care to patients who have a specific tumour type. They are written by European experts representing all disciplines involved in cancer care. ERQCC papers give oncology teams, patients, policymakers and managers an overview of the elements needed in any healthcare system to provide high quality of care throughout the patient journey. References are made to clinical guidelines and other resources where appropriate, and the focus is on care in Europe. Colorectal cancer: essential requirements for quality care CONCLUSION: Taken together, the information presented in this paper provides a comprehensive description of the essential requirements for establishing a high-quality CRC service. The ECCO expert group is aware that it is not possible to propose a 'one size fits all' system for all countries, but urges that access to multidisciplinary units or centres must be guaranteed for all those with CRC.

Tamalet C, Ravaux I, Dhiver C, et al.
Feasibility and Acceptability of Anal Self-Sampling for Human Papillomavirus Screening in HIV-Infected Patients.
Intervirology. 2016; 59(2):118-122 [PubMed] Related Publications
OBJECTIVES: Anal cancer incidence is increasing among HIV-positive patients. No consensus currently exists for the screening of anal dysplasia. This study aimed at evaluating the feasibility and acceptability of anal self-sampling and assessing the prevalence of human papillomavirus (HPV) types among HIV-positive patients from Marseille University Hospitals.
METHODS: Between October 2013 and March 2014, during their regular visits for the monitoring of their HIV infection in an HIV outpatient clinical unit of Marseille University Hospitals, patients were asked to self-sample anal swabs for HPV detection. A specimen self-collection kit was provided. HPV detection and genotyping were performed using in-house protocols. The quality of self-sampling was assessed by concurrent cellular quantification in collected samples.
RESULTS: The acceptability rate of anal self-sampling was 91%, and 91% of the self-sampled specimens were appropriate for HPV screening. In addition, 76% of the samples were positive for HPV, including 54% of HPV types with oncogenic potential.
CONCLUSIONS: This study indicates that HPV detection and typing through anal self-sampling is a valuable strategy to screen patients at high risk for anal cancer development. This could allow earlier management of anal lesions and related cancer in patients at high risk for HPV.

Kahouli I, Malhotra M, Westfall S, et al.
Design and validation of an orally administrated active L. fermentum-L. acidophilus probiotic formulation using colorectal cancer Apc (Min/+) mouse model.
Appl Microbiol Biotechnol. 2017; 101(5):1999-2019 [PubMed] Related Publications
Probiotics have been shown to have beneficial properties in attenuating the risk of colorectal cancer (CRC) development. However, functional evidence to support such effects for some probiotic bacteria are relatively unknown. Here, we document a significant antioxidant, anti-proliferative and pro-apoptotic activities of Lactobacillus acidophilus ATCC 314 and Lactobacillus fermentum NCIMB 5221 on CRC cells, particularly when used in combination (La-Lf). Furthermore, a superior synergistic activity on the inhibition of tumor growth and modulation of cell proliferation and epithelial markers in the Apc (Min/+) CRC mouse model was explored, based on the expression levels of Ki-67, E-cadherin, β-catenin, and cleaved caspase-3 (CC3) proteins. The anti-cancer activity of La-Lf co-culture was significantly enhanced in vitro with significant reduced proliferation (38.8 ± 6.9 %, P = 0.009) and increased apoptosis (413 RUL, P < 0.001) towards cancer cells, as well as significant protection of normal colon cell growth from toxic treatment (18.6 ± 9.8 %, P = 0.001). La-Lf formulation (10(10)cfu/animal/day) altered aspects of intestinal tumorigenesis by significantly reducing intestinal tumor multiplicity (1.7-fold, P = 0.016) and downregulating cellular proliferation markers, including β-catenin (P = 0.041) and Ki-67 (P = 0.008). In conclusion, La-Lf showed greater protection against intestinal tumorigenesis supporting a potential use as a biotherapeutic for the prevention of CRC.

Wang L, Hu X, Xu Y, Liu Z
Arsenic trioxide inhibits lung metastasis of mouse colon cancer via reducing the infiltration of regulatory T cells.
Tumour Biol. 2016; 37(11):15165-15173 [PubMed] Free Access to Full Article Related Publications
The purpose of this study was to investigate the effects of arsenic trioxide (As2O3) on the infiltration of regulatory T cells (Tregs) in the local lung metastasis of mouse colon cancer in vivo and the regulation of Tregs in cytokine-induced killer cells (CIKs) in vitro. A high Tregs infiltration mouse colon cancer lung metastasis model was established by intravenous injection of CT26 murine colon carcinoma cells. Tumor-bearing mice were randomly divided into three groups: control group, low-dose As2O3 group, and high-dose As2O3 group. For in vitro studies, CIKs were treated with vehicle control or 0.1, 1, or 5 μM As2O3. The level of Tregs was detected via flow cytometry, Foxp3 expression was assessed by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR), the level of interferon gamma (IFN-γ) was evaluated by enzyme-linked immunoassay (ELISA), and the cytotoxic activity of As2O3-treated CIKs was assessed through a lactate dehydrogenase (LDH) release assay. Obvious lung metastasis was observed 3 days after CT26 murine colon carcinoma cell injection. The numbers of Tregs in the lungs and spleens of tumor-bearing mice were significantly higher than those of the normal group (p < 0.01). As2O3 treatment increased the mouse weight as well as reduced the number of metastatic lung nodules and the lung/body weight ratio (p < 0.01). Moreover, As2O3 treatment significantly reduced the Tregs proportion and the Foxp3 messenger RNA (mRNA) levels in metastatic lung tissues (p < 0.01). In vitro, As2O3 significantly reduced the Tregs proportion and the Foxp3 mRNA levels (p < 0.01) and significantly increased the cytotoxic activity of CIKs and the IFN-γ levels in the supernatant of cultured CIKs (p < 0.01). As2O3 might inhibit lung metastasis of colon cancer by reducing the local infiltration of Tregs and increase the cytotoxic activity of CIKs by suppressing Tregs.

Tze CN, Fitzgerald H, Qureshi A, et al.
Pioneering Annual Colorectal Cancer Screening and Treatment Targeting Low Income Communities in Malaysia (20102015).
Asian Pac J Cancer Prev. 2016; 17(7):3179-83 [PubMed] Related Publications
The aim of this study was to assess the rate of uptake of a customised annual Colorectal Cancer Awareness, Screening and Treatment Project (CCASTP) using faecal immunohistochemical test (FIT) kits in low income communities in Malaysia. The immediate objectives were (1) to evaluate the level of adherence of CRC screening among lowincome groups, (2) to assess the knowledge and awareness of the screened population and (3) to assess the accuracy of FIT kits. A total of 1,581 FIT kits were distributed between years 2010 to 2015 to healthy asymptomatic participants of the annual CCASTP organized by Empowered the Cancer Advocacy Society of Malaysia. Data for sociodemographic characteristics, critical health and lifestyle information of the registered subjects were collected. Findings for use of the FIT kits were collected when they were returned for stool analyses. Those testingd positive were invited to undergo a colonoscopy examination. A total of 1,436 (90.8%) of the subjects retuned the FITkits, showing high compliance. Among the 129 subjects with positive FIT results, 92 (71.3%) underwent colonoscopy. Six cases (6.5%) of CRC were found. Based on the data collected, the level of awareness of stool examination and knowledge about CRC was poor amongst the participants. Gender, age group, ethnicity and risk factors (i.e. smoking, lack of exercise and low consumption of fresh fruits) were associated with positive FITkit results. In conclusion, CRC screening can be performed in the community with a single FITkit. Although CRC knowledge and awareness is poor in lowincome communities, the average return rate of the FIT kits and rate of colonoscopy examination were 91.2% and 70.3%, respectively.

Nguyen BH, Luong NT, Lehr KT, et al.
Community Participation in Health Disparity Intervention Research in Vietnamese American Community.
Prog Community Health Partnersh. 2016; 10(2):207-15 [PubMed] Related Publications
BACKGROUND: A community-based participatory research (CBPR) project used a lay health worker (LHW) intervention to reduce colorectal cancer screening disparities in the Vietnamese American community.
OBJECTIVES: The study seeks to understand how the community participates in the CBPR project from the perspectives of diverse stakeholders.
METHODS: Qualitative interviews were conducted with 13 community leaders, community-based organization (CBO) representatives, LHW coordinators, and researchers. Interview topics included participation context, expectations, partnership dynamics, benefits, challenges, and community impact. Interviews were audio-recorded and transcribed verbatim. Data analysis used grounded theory.
RESULTS: Community participation was built on trust and relationships that were cultivated and nurtured over decades. This is the first study to document that Vietnamese Americans preferred an informal partnership style, but expected researchers to understand community health issues, norms, and collaboration styles.
CONCLUSIONS: CBPR in underserved communities has their own styles, expectations, benefits, and challenges. Understanding these issues is critical in engaging the community.

Singh Ranger G
The role of aspirin in colorectal cancer chemoprevention.
Crit Rev Oncol Hematol. 2016; 104:87-90 [PubMed] Related Publications
Considerable interest has emerged over the last decade regarding the role of aspirin in prevention of colorectal cancer. This disease is one of the commonest cancers in the Western World, therefore, the existence of a simple "everyday" agent, which could have the ability to prevent the disease, represents an invaluable opportunity clinicians may be able to exploit. Evidence from case-control and cohort studies, and recent updates of randomised controlled trials have been very encouraging-indicating benefit from long term use of aspirin at low dose. Possible mechanisms of chemoprevention include inhibition of the cyclooxygenase (COX) pathway, or COX-independent mechanisms, for example, the PIK3CA pathway, or therapy-induced senescence of cancer cells. The most serious side effect of prolonged aspirin treatment is haemorrhage, especially from the GI tract. This is likely to be less of a problem with chemoprevention at lower doses. One also needs to consider the impact if aspirin resistance, an increasingly recognised clinical entity.

Imran M, Sayedalamin Z, Alsulami SS, et al.
Knowledge and Awareness of Colorectal Cancer among Undergraduate Students at King Abdulaziz University, Jeddah, Saudi Arabia: a Survey-Based Study.
Asian Pac J Cancer Prev. 2016; 17(5):2479-83 [PubMed] Related Publications
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 (<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.

Schmit SL, Rennert HS, Rennert G, Gruber SB
Coffee Consumption and the Risk of Colorectal Cancer.
Cancer Epidemiol Biomarkers Prev. 2016; 25(4):634-9 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
BACKGROUND: Coffee contains several bioactive compounds relevant to colon physiology. Although coffee intake is a proposed protective factor for colorectal cancer, current evidence remains inconclusive.
METHODS: We investigated the association between coffee consumption and risk of colorectal cancer in 5,145 cases and 4,097 controls from the Molecular Epidemiology of Colorectal Cancer (MECC) study, a population-based case-control study in northern Israel. We also examined this association by type of coffee, by cancer site (colon and rectum), and by ethnic subgroup (Ashkenazi Jews, Sephardi Jews, and Arabs). Coffee data were collected by interview using a validated, semi-quantitative food frequency questionnaire.
RESULTS: Coffee consumption was associated with 26% lower odds of developing colorectal cancer [OR (drinkers vs. non-drinkers), 0.74; 95% confidence interval (CI), 0.64-0.86; P < 0.001]. The inverse association was also observed for decaffeinated coffee consumption alone (OR, 0.82; 95% CI, 0.68-0.99; P = 0.04) and for boiled coffee (OR, 0.82; 95% CI, 0.71-0.94; P = 0.004). Increasing consumption of coffee was associated with lower odds of developing colorectal cancer. Compared with <1 serving/day, intake of 1 to <2 servings/day (OR, 0.78; 95% CI, 0.68-0.90; P < 0.001), 2 to 2.5 servings/day (OR, 0.59; 95% CI, 0.51-0.68; P < 0.001), and >2.5 servings/day (OR, 0.46; 95% CI, 0.39-0.54; P < 0.001) were associated with significantly lower odds of colorectal cancer (Ptrend < 0.001), and the dose-response trend was statistically significant for both colon and rectal cancers.
CONCLUSIONS: Coffee consumption may be inversely associated with risk of colorectal cancer in a dose-response manner.
IMPACT: Global coffee consumption patterns suggest potential health benefits of the beverage for reducing the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 25(4); 634-9. ©2016 AACR.

Filippi MK, Perdue DG, Hester C, et al.
J Cult Divers. 2016; 23(1):21-7 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality. Effective prevention and early detection may be achieved through screening, but screening rates are low, especially in American Indian (AI) populations. We wanted to understand perceptions of CRC screening among AI located in the Great Lakes region. Focus groups were recorded and transcribed verbatim (N = 45). Data were analyzed using qualitative text analysis. Themes that deterred CRC screening were low CRC knowledge, fear of the procedure and results, cost and transportation issues, and a lack of quality and competent care. Suggestions for improvement included outreach efforts and culturally-tailored teaching materials.

Nie Z, Zhu H, Gu M
Reduced colorectal cancer incidence in type 2 diabetic patients treated with metformin: a meta-analysis.
Pharm Biol. 2016; 54(11):2636-2642 [PubMed] Related Publications
CONTEXT: Diabetic patients have a higher risk of colorectal cancer (CRC). The role of metformin in CRC incidence among type 2 diabetes mellitus (T2DM) remains controversial.
OBJECTIVE: A meta-analysis was performed to evaluate the role of metformin treatment in the occurrence of CRC among T2DM patients.
METHODS: Search was performed throughout PubMed, Embase, Springer databases up to November 2014. The search terms were (biguanides or metformin) and (bowel or colon or rectal or colorectal) and (cancer or neoplasm or neoplasia). Relative risk (RR) and 95% confidence interval (CI) was pooled using random-effects model or fixed-effect model basing on heterogeneity, which was calculated basing on Q statistics and χ(2) test. In addition, subgroup analyses were performed according to region, study design and control treatment. Finally, publication bias was evaluated using Egger's regression test and trim and fill analysis.
RESULTS: A total of 11 studies, including eight cohort studies and three case-control studies, were enrolled in the meta-analysis. Obvious heterogeneity was noted, and a 25% lower CRC incidence was found among diabetic patients treated with metformin (pooled RR=0.75, 95% CI: 0.66-0.86), using the random-effects model. Subgroup analyses showed that CRC incidence significantly reduced among T2DM in different regions, non-metformin treatment and cohort studies. Evidence supported significant publication for studies investigating from Egger's regression test. Conversely, no missing data were found using trim and fill analysis.
CONCLUSION: In conclusion, the meta-analysis suggests metformin may reduce CRC incidence among diabetics, which is useful medical information for clinicians.

Tian Y, Wang K, Fan Y, et al.
Chemopreventive Effect of Dietary Glutamineon Colitis-Associated Colorectal Cancer Is Associated with Modulation of the DEPTOR/mTOR Signaling Pathway.
Nutrients. 2016; 8(5) [PubMed] Article available free on PMC after 01/04/2017 Related Publications
Glutamine plays a protective role in colitis and colitis-associated colorectal cancer (CAC); however, the protective mechanisms are largely unknown to date. DEP domain-containing mTOR-interacting protein (DEPTOR)/mammalian Target of Rapamycin (mTOR) signaling plays an important role in carcinogenesis. The present study investigated the potential molecular mechanisms for the protective effect of glutamine in a murine model of azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CAC. The effects of glutamine on DEPTOR/mTOR signaling and protein light chain 3 (LC3) were evaluated. Administration of glutamine was associated with attenuated development of CAC. Increased expression of DEPTOR and decreased expressions of factors of mTOR signaling, including phospho-mTOR, phospho-STAT3, phospho-Akt, and phospho-S6, were observed in AOM/DSS mice administered glutamine. Furthermore, oral glutamine was associated with increased LC3-II expression in AOM/DSS mice. The present study indicates that regulation of DEPTOR/mTOR signaling may be an important mechanism for glutamine in prevention against the development of CAC. In addition, the chemopreventive effect of dietary glutamine on CAC is, at least in part, associated with the induction of autophagy.

Mukkai Krishnamurty D, Wise PE
Importance of surgical margins in rectal cancer.
J Surg Oncol. 2016; 113(3):323-32 [PubMed] Related Publications
Distal resection margin (DRM) and circumferential resection margin (CRM) are two important considerations in rectal cancer management. Although guidelines recommend a 2 cm DRM, studies have shown that a shorter DRM is adequate, especially in patients receiving neoadjuvant chemoradiation. Standardization of total mesorectal excision has greatly improved quality of CRM. Although more patients are undergoing sphincter-saving procedures, abdominoperineal resection is indicated for very distal tumors, and pelvic exenteration is often necessary for tumors involving pelvic organs.

Bounaama A, Enayat S, Ceyhan MS, et al.
Ethanolic Extract of Bark from Salix aegyptiaca Ameliorates 1,2-dimethylhydrazine-induced Colon Carcinogenesis in Mice by Reducing Oxidative Stress.
Nutr Cancer. 2016; 68(3):495-506 [PubMed] Related Publications
We have previously shown that ethanolic extract from bark (EEB) of Salix aegyptiaca (Musk Willow) can inhibit proliferation and motility and induce apoptosis in colon cancer cells. Tandem mass spectrometry revealed EEB to be rich in catechin, catechol, and salicin. The present study investigated the chemopreventive effect of HPLC-fingerprinted EEB on 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) formation in mice. DMH (20 mg/kg body weight) was weekly injected subcutaneously to mice for the first 2 weeks. EEB (100 and 400 mg/kg body weight) was provided orally from the 7th to 14th week, after which colon tissues were evaluated histologically and biochemically. DMH treatment induced high number of ACF; EEB significantly reduced the number and multiplicity of ACF, along with a restoration in goblet cells and mucin accumulation. EEB supplementation improved the markers of inflammation (myeloperoxidase and neutrophil infiltration) and oxidative stress. More importantly, EEB amplified apoptosis of neoplastic cells in the colon mucosa of DMH-treated mice. It also lowered levels of markers for early transformation events such as EGFR, nuclear β-catenin, and COX-2 in colon cancer cell lines HT-29 and HCT-116. The innocuity of EEB (up to 1600 mg/kg) to mice reinforces its potential as a chemopreventive agent.

Ma H, Pan JS, Jin LX, et al.
MicroRNA-17~92 inhibits colorectal cancer progression by targeting angiogenesis.
Cancer Lett. 2016; 376(2):293-302 [PubMed] Related Publications
The miR-17~92 microRNA (miRNA) cluster host gene is upregulated in a broad spectrum of human cancers including colorectal cancer (CRC). Previous studies have shown that miR-17~92 promotes tumorigenesis and cancer angiogenesis in some tumor models. However, its role in the initiation and progression of CRC remains unknown. In this study, we found that transgenic mice overexpressing miR-17~92 specifically in epithelial cells of the small and large intestines exhibited decreased tumor size and tumor angiogenesis in azoxymethane and dextran sulfate sodium salt (AOM-DSS)-induced CRC model as compared to their littermates control. Further study showed that miR-17~92 inhibited the progression of CRC via suppressing tumor angiogenesis through targeting multiple tumor angiogenesis-inducing genes, TGFBR2, HIF1α, and VEGFA in vivo and in vitro. Collectively, we demonstrated that miR-17~92 suppressed tumor progression by inhibiting tumor angiogenesis in a genetically engineered mouse model, indicating the presence of cellular context-dependent pro- and anti-cancer effects of miR-17~92.

Burr NE, Hull MA, Subramanian V
Does aspirin or non-aspirin non-steroidal anti-inflammatory drug use prevent colorectal cancer in inflammatory bowel disease?
World J Gastroenterol. 2016; 22(13):3679-86 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
AIM: To determine whether aspirin or non-aspirin non-steroidal anti-inflammatory drugs (NA-NSAIDs) prevent colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD).
METHODS: We performed a systematic review and meta-analysis. We searched for articles reporting the risk of CRC in patients with IBD related to aspirin or NA-NSAID use. Pooled odds ratios (OR) and 95%CIs were determined using a random-effects model. Publication bias was assessed using Funnel plots and Egger's test. Heterogeneity was assessed using Cochran's Q and the I (2) statistic.
RESULTS: Eight studies involving 14917 patients and 3 studies involving 1282 patients provided data on the risk of CRC in patients with IBD taking NA-NSAIDs and aspirin respectively. The pooled OR of developing CRC after exposure to NA-NSAIDs in patients with IBD was 0.80 (95%CI: 0.39-1.21) and after exposure to aspirin it was 0.66 (95%CI: 0.06-1.39). There was significant heterogeneity (I (2) > 50%) between the studies. There was no change in the effect estimates on subgroup analyses of the population studied or whether adjustment or matching was performed.
CONCLUSION: There is a lack of high quality evidence on this important clinical topic. From the available evidence NA-NSAID or aspirin use does not appear to be chemopreventative for CRC in patients with IBD.

Weidner C, Rousseau M, Plauth A, et al.
Iberis amara Extract Induces Intracellular Formation of Reactive Oxygen Species and Inhibits Colon Cancer.
PLoS One. 2016; 11(4):e0152398 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
Massively increasing global incidences of colorectal cancer require efficient treatment and prevention strategies. Here, we report unexpected anticancerogenic effects of hydroethanolic Iberis amara extract (IAE), which is known as a widely used phytomedical product for treating gastrointestinal complaints. IAE significantly inhibited the proliferation of HT-29 and T84 colon carcinoma cells with an inhibitory concentration (IC50) of 6 and 9 μg/ml, respectively, and further generated inhibitory effects in PC-3 prostate and MCF7 breast cancer cells. Inhibition of proliferation in HT-29 cells was associated with a G2/M phase cell cycle arrest including reduced expression of various regulatory marker proteins. Notably, in HT-29 cells IAE further induced apoptosis by intracellular formation of reactive oxygen species (ROS). Consistent with predictions derived from our in vitro experiments, bidaily oral gavage of 50 mg/kg of IAE over 4 weeks resulted in significant inhibition of tumor growth in a mouse HT-29 tumor xenograft model. Taken together, Iberis amara extracts could become useful alternatives for preventing and treating the progression of colon cancer.

Ambalam P, Raman M, Purama RK, Doble M
Probiotics, prebiotics and colorectal cancer prevention.
Best Pract Res Clin Gastroenterol. 2016; 30(1):119-31 [PubMed] Related Publications
Colorectal cancer (CRC), the third major cause of mortality among various cancer types in United States, has been increasing in developing countries due to varying diet and dietary habits and occupational hazards. Recent evidences showed that composition of gut microbiota could be associated with the development of CRC and other gut dysbiosis. Modulation of gut microbiota by probiotics and prebiotics, either alone or in combination could positively influence the cross-talk between immune system and microbiota, would be beneficial in preventing inflammation and CRC. In this review, role of probiotics and prebiotics in the prevention of CRC has been discussed. Various epidemiological and experimental studies, specifically gut microbiome research has effectively improved the understanding about the role of probiotics and microbial treatment as anticarcinogenic agents. A few human studies support the beneficial effect of probiotics and prebiotics; hence, comprehensive understanding is urgent to realize the clinical applications of probiotics and prebiotics in CRC prevention.

Pines A
Hormone therapy and large bowel cancer revisited.
Climacteric. 2016; 19(3):247-8 [PubMed] Related Publications
Many studies have investigated potential links between postmenopausal hormone therapy (HT) and the risk for colorectal cancer. Most of these studies showed some reduction in risk, but association with the exact grade of the tumor or with cancer mortality is less consistent. Activation of estrogen receptor beta (ERβ) related cellular pathways is probably the pathophysiological basis for this HT effect, since ERβs exert antiproliferative and pro-apoptotic signaling, inhibit inflammatory signaling and modulate the tumor microenvironment. To note, the impact on health may not be substantial as the absolute numbers point at the order of only a few saved cases per 10 000 women per year of hormone use.

Wilson N, Selak V, Blakely T, et al.
Decision-making in an era of cancer prevention via aspirin: New Zealand needs updated guidelines and risk calculators.
N Z Med J. 2016; 129(1431):85-92 [PubMed] Related Publications
Based on new systematic reviews of the evidence, the US Preventive Services Task Force has drafted updated guidelines on the use of low-dose aspirin for the primary prevention of both cardiovascular disease (CVD) and cancer. The Task Force generally recommends consideration of aspirin in adults aged 50-69 years with 10-year CVD risk of at least 10%, in who absolute health gain (reduction of CVD and cancer) is estimated to exceed absolute health loss (increase in bleeds). With the ongoing decline in CVD, current risk calculators for New Zealand are probably outdated, so it is difficult to be precise about what proportion of the population is in this risk category (roughly equivalent to 5-year CVD risk ≥5%). Nevertheless, we suspect that most smokers aged 50-69 years, and some non-smokers, would probably meet the new threshold for taking low-dose aspirin. The country therefore needs updated guidelines and risk calculators that are ideally informed by estimates of absolute net health gain (in quality-adjusted life-years (QALYs) per person) and cost-effectiveness. Other improvements to risk calculators include: epidemiological rigour (eg, by addressing competing mortality); providing enhanced graphical display of risk to enhance risk communication; and possibly capturing the issues of medication disutility and comparison with lifestyle changes.

Huang WK, Hsu HC, Liu JR, et al.
The Association of Ursodeoxycholic Acid Use With Colorectal Cancer Risk: A Nationwide Cohort Study.
Medicine (Baltimore). 2016; 95(11):e2980 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
Data from preclinical studies suggest that ursodeoxycholic acid (UDCA) has a chemopreventive effect on colorectal cancer (CRC) development, but no large observational study has examined this possibility. The aim of this study was to investigate the association of UDCA use with CRC risk in a nationwide population-based cohort. This nationwide population-based cohort study used data from the Taiwan National Health Insurance Research Database for the period from 2000 through 2010. This study included data from 7119 Taiwanese adults who received ≥28 cumulative defined daily doses (cDDDs) of UDCA and 14,238 patients who did not receive UDCA (<28 cDDDs). UDCA nonusers were matched 1:2 for age, sex, enrollment date, and presence of chronic liver disease, viral hepatitis, cholelithiasis, and alcoholic liver disease. The 2 cohorts were followed until December 31, 2010 or occurrence of CRC. Cox proportional hazards regression with robust Sandwich variance estimator, which can cooperate with matching design, was used to examine the association between UDCA use and CRC risk. During 109,312 person-years of follow-up (median, 5 years), 121 patients had newly diagnosed CRC: 28 UDCA users (76.7 per 100,000 person-years) and 93 nonusers (127.7 per 100,000 person-years) (log-rank test, P = 0.0169). After multivariate adjustment for age, UDCA use was associated with a reduced risk of CRC (hazard ratio, 0.60; 95% confidence interval [CI], 0.39-0.92). The adjusted hazard ratios were 0.55 (95% CI, 0.35-0.89), 0.89 (95% CI, 0.36-2.20), and 0.63 (95% CI, 0.16-2.53) for patients with 28 to 180, 181 to 365, and >365 cDDDs, respectively, relative to nonusers. UDCA use was associated with reduced risk of CRC in a cohort mainly comprising patients with chronic liver diseases. However, further studies are needed to determine the optimal dosage of UDCA.

Wojtowicz ME, Dunn BK, Umar A
Immunologic approaches to cancer prevention-current status, challenges, and future perspectives.
Semin Oncol. 2016; 43(1):161-72 [PubMed] Related Publications
The potential of the immune system to recognize and reject tumors has been investigated for more than a century. However, only recently impressive breakthroughs in cancer immunotherapy have been seen with the use of checkpoint inhibitors. The experience with various immune-based strategies in the treatment of late cancer highlighted the importance of negative impact advanced disease has on immunity. Consequently, use of immune modulation for cancer prevention rather than therapy has gained considerable attention, with many promising results seen already in preclinical and early clinical studies. Although not without challenges, these results provide much excitement and optimism that successful cancer immunoprevention could be within our reach. In this review we will discuss the current state of predominantly primary and secondary cancer immunoprevention, relevant research, potential barriers, and future directions.

Walcott FL, Patel J, Lubet R, et al.
Hereditary cancer syndromes as model systems for chemopreventive agent development.
Semin Oncol. 2016; 43(1):134-45 [PubMed] Related Publications
Research in chemoprevention has undergone a shift in emphasis for pragmatic reasons from large, phase III randomized studies to earlier phase studies focused on safety, mechanisms, and utilization of surrogate endpoints such as biomarkers instead of cancer incidence. This transition permits trials to be conducted in smaller populations and at substantially reduced costs while still yielding valuable information. This article will summarize some of the current chemoprevention challenges and the justification for the use of animal models to facilitate identification and testing of chemopreventive agents as illustrated though four inherited cancer syndromes. Preclinical models of inherited cancer syndromes serve as prototypical systems in which chemopreventive agents can be developed for ultimate application to both the sporadic and inherited cancer settings.

Bultman SJ
The microbiome and its potential as a cancer preventive intervention.
Semin Oncol. 2016; 43(1):97-106 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
It is becoming increasingly clear that microbiota inhabiting our bodies influence cancer predisposition and etiology. In addition to pathogens with oncogenic properties, commensal and symbiotic microbiota have tumor-suppressive properties. Diet and other environmental factors can modulate the abundance of certain members of microbial communities within the gastrointestinal tract and at other anatomical sites. Furthermore, some dietary factors are metabolized by commensal/symbiotic gut microbiota into bioactive food components believed to prevent cancer. For example, dietary fiber undergoes bacterial fermentation in the colon to yield butyrate, which is a short-chain fatty acid and histone deacetylase (HDAC) inhibitor that suppresses the viability and growth of colorectal cancer cell lines. A recent study using gnotobiotic mouse models demonstrates that fiber can protect against colorectal tumorigenesis in a microbiota- and butyrate-dependent manner that involves the Warburg effect. This and other examples suggest that some of the inter-individual variation observed in epidemiology and intervention studies that have investigated associations between diet and cancer risk might be explained by differences in microbiota among the participants. Data from basic research studies also support the idea that probiotics and prebiotics could be plausible chemoprevention strategies that may be utilized to a greater extent in the future.

Mensah FA, Mehta MR, Lewis JS, Lockhart AC
The Human Papillomavirus Vaccine: Current Perspective and Future Role in Prevention and Treatment of Anal Intraepithelial Neoplasia and Anal Cancer.
Oncologist. 2016; 21(4):453-60 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
UNLABELLED: The incidences of human papillomavirus (HPV)-related anal cancer and its precursor lesion, anal intraepithelial neoplasia, are rising in the U.S. and globally. Five-year survival rates with current modalities of treatment for anal cancer are generally favorable for localized and regional disease. For metastatic disease, the relative survival rate is poor. Major contributing factors for the increase in anal cancer incidence include increasing receptive anal intercourse (hetero- and homosexual), increasing HPV infections, and longer life expectancy of treated people who are seropositive for human immunodeficiency virus. Because treatment outcomes with systemic therapy in patients with advanced disease are so poor, prevention may be the best approach for reducing disease burden. The association of a major causative agent with anal cancer provides an excellent opportunity for prevention and treatment. The advent of the HPV vaccine for anal cancer prevention and treatment is a significant milestone and has the potential to greatly impact these cancers. The data regarding potential use of the HPV vaccine in anal cancer prevention and treatment are reviewed.
IMPLICATIONS FOR PRACTICE: The incidences of human papillomavirus (HPV)-related anal cancer and its precursor lesion, anal intraepithelial neoplasia, are on the rise in the U.S. and globally. Based on recent studies, the HPV vaccine is approved for prevention of the infection and development of HPV-related anal cancer. In addition, several small studies have shown that the vaccine may be useful as adjuvant therapy for anal cancer. There is a need for public health strategies aimed at education of both patients and practitioners to improve the use of the vaccine for prevention of HPV-related anal cancer. The development of a therapeutic vaccine is a work in progress.

Yu T, Xu B, He L, et al.
Pigment epithelial-derived factor gene loaded novel COOH-PEG-PLGA-COOH nanoparticles promoted tumor suppression by systemic administration.
Int J Nanomedicine. 2016; 11:743-59 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
Anti-angiogenesis has been proposed as an effective therapeutic strategy for cancer treatment. Pigment epithelium-derived factor (PEDF) is one of the most powerful endogenous anti-angiogenic reagents discovered to date and PEDF gene therapy has been recognized as a promising treatment option for various tumors. There is an urgent need to develop a safe and valid vector for its systemic delivery. Herein, a novel gene delivery system based on the newly synthesized copolymer COOH-PEG-PLGA-COOH (CPPC) was developed in this study, which was probably capable of overcoming the disadvantages of viral vectors and cationic lipids/polymers-based nonviral carriers. PEDF gene loaded CPPC nanoparticles (D-NPs) were fabricated by a modified double-emulsion water-in-oil-in-water (W/O/W) solvent evaporation method. D-NPs with uniform spherical shape had relatively high drug loading (~1.6%), probably because the introduced carboxyl group in poly (D,L-lactide-co-glycolide) terminal enhanced the interaction of copolymer with the PEDF gene complexes. An excellent in vitro antitumor effect was found in both C26 and A549 cells treated by D-NPs, in which PEDF levels were dramatically elevated due to the successful transfection of PEDF gene. D-NPs also showed a strong inhibitory effect on proliferation of human umbilical vein endothelial cells in vitro and inhibited the tumor-induced angiogenesis in vivo by an alginate-encapsulated tumor cell assay. Further in vivo antitumor investigation, carried out in a C26 subcutaneous tumor model by intravenous injection, demonstrated that D-NPs could achieve a significant antitumor activity with sharply reduced microvessel density and significantly promoted tumor cell apoptosis. Additionally, the in vitro hemolysis analysis and in vivo serological and biochemical analysis revealed that D-NPs had no obvious toxicity. All the data indicated that the novel CPPC nanoparticles were ideal vectors for the systemic delivery of PEDF gene and might be widely used as systemic gene vectors.

Brenner H, Schrotz-King P, Holleczek B, et al.
Declining Bowel Cancer Incidence and Mortality in Germany.
Dtsch Arztebl Int. 2016; 113(7):101-6 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
BACKGROUND: In October 2002, screening colonoscopy from age 55 onward was introduced as part of the German national statutory cancer screening program. Screening colonoscopy is intended to lower both the mortality and the incidence of bowel cancer by enabling the detection and removal of precursor lesions.
METHODS: The authors studied trends in bowel cancer incidence and mortality in Germany from 2003 to 2012 on the basis of data from the epidemiological cancer registries and from cause-of-death statistics.
RESULTS: Over the period of investigation, the age-standardized incidence of bowel cancer (with the European population as a standard) fell from 66.1 to 57.0 cases per 100 000 persons per year (-13.8%) in men and from 42.6 to 36.5 per 100 000 persons per year (-14.3%) in women. In parallel with these changes, the age-standardized mortality from bowel cancer fell by 20.8% in men and by 26.5% in women. In the age groups 55-64, 65-74, and 75-84 years, the cumulative risk of receiving a diagnosis of bowel cancer fell by 17-26%; in persons under age 55, this risk fell by only 3% in men, but increased by 14% in women. Long-term data from the cancer registry in the German federal state of Saarland revealed that the incidence of bowel cancer, but not its mortality, had risen over the decades preceding the study; it was only during the period of investigation that the trend reversed itself.
CONCLUSION: Within 10 years of the introduction of screening colonoscopy in Germany, the incidence of bowel cancer in persons over age 55 fell by 17-26%, after having risen steadily over the preceding decades.

Cao Y, Nishihara R, Wu K, et al.
Population-wide Impact of Long-term Use of Aspirin and the Risk for Cancer.
JAMA Oncol. 2016; 2(6):762-9 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
IMPORTANCE: The US Preventive Services Task Force recently recommended the use of aspirin to prevent colorectal cancer and cardiovascular disease among many US adults. However, the association of aspirin use with the risk for other cancer types and the potential population-wide effect of aspirin use on cancer, particularly within the context of screening, remain uncertain.
OBJECTIVES: To examine the potential benefits of aspirin use for overall and subtype-specific cancer prevention at a range of doses and durations of use and to estimate the absolute benefit of aspirin in the context of screening.
DESIGN, SETTING, AND PARTICIPANTS: Two large US prospective cohort studies, the Nurses' Health Study (1980-2010) and Health Professionals Follow-up Study (1986-2012), followed up 135 965 health care professionals (88 084 women and 47 881 men, respectively) who reported on aspirin use biennially. The women were aged 30 to 55 years at enrollment in 1976; the men, aged 40 to 75 years in 1986. Final follow-up was completed on June 30, 2012, for the Nurses' Health Study cohort and January 31, 2010, for the Health Professionals Follow-up Study cohort, and data were accessed from September 15, 2014, to December 17, 2015.
MAIN OUTCOMES AND MEASURES: Relative risks (RRs) for incident cancers and population-attributable risk (PAR).
RESULTS: Among the 88 084 women and 47 881 men who underwent follow-up for as long as 32 years, 20 414 cancers among women and 7571 cancers among men were documented. Compared with nonregular use, regular aspirin use was associated with a lower risk for overall cancer (RR, 0.97; 95% CI, 0.94-0.99), which was primarily owing to a lower incidence of gastrointestinal tract cancers (RR, 0.85; 95% CI, 0.80-0.91), especially colorectal cancers (RR, 0.81; 95% CI, 0.75-0.88). The benefit of aspirin on gastrointestinal tract cancers appeared evident with the use of at least 0.5 to 1.5 standard aspirin tablets per week; the minimum duration of regular use associated with a lower risk was 6 years. Among individuals older than 50 years, regular aspirin use could prevent 33 colorectal cancers per 100 000 person-years (PAR, 17.0%) among those who had not undergone a lower endoscopy and 18 colorectal cancers per 100 000 person-years (PAR, 8.5%) among those who had. Regular aspirin use was not associated with the risk for breast, advanced prostate, or lung cancer.
CONCLUSIONS AND RELEVANCE: Long-term aspirin use was associated with a modest but significantly reduced risk for overall cancer, especially gastrointestinal tract tumors. Regular aspirin use may prevent a substantial proportion of colorectal cancers and complement the benefits of screening.

Joseph DA, Redwood D, DeGroff A, Butler EL
Use of Evidence-Based Interventions to Address Disparities in Colorectal Cancer Screening.
MMWR Suppl. 2016; 65(1):21-8 [PubMed] Related Publications
Colorectal cancer (CRC) is the second leading cause of cancer death among cancers that affect both men and women. Despite strong evidence of their effectiveness, CRC screening tests are underused. Racial/ethnic minority groups, persons without insurance, those with lower educational attainment, and those with lower household income levels have lower rates of CRC screening. Since 2009, CDC's Colorectal Cancer Control Program (CRCCP) has supported state health departments and tribal organizations in implementing evidence-based interventions (EBIs) to increase use of CRC screening tests among their populations. This report highlights the successful implementation of EBIs to address disparities by two CRCCP grantees: the Alaska Native Tribal Health Consortium (ANTHC) and Washington State's Breast, Cervical, and Colon Health Program (BCCHP). ANTHC partnered with regional tribal health organizations in the Alaska Tribal Health System to implement provider and client reminders and use patient navigators to increase CRC screening rates among Alaska Native populations. BCCHP identified patient care coordinators in each clinic who coordinated staff training on CRC screening and integrated client and provider reminder systems. In both the Alaska and Washington programs, instituting provider reminder systems, client reminder systems, or both was facilitated by use of electronic health record systems. Using multicomponent interventions in a single clinical site or facility can support more organized screening programs and potentially result in greater increases in screening rates than relying on a single strategy. Organized screening systems have an explicit policy for screening, a defined target population, a team responsible for implementation of the screening program, and a quality assurance structure. Although CRC screening rates in the United States have increased steadily over the past decade, this increase has not been seen equally across all populations. Increasing the use of EBIs, such as those described in this report, in health care clinics and systems that serve populations with lower CRC screening rates could substantially increase CRC screening rates.

Schoenberg NE, Eddens K, Jonas A, et al.
Colorectal cancer prevention: Perspectives of key players from social networks in a low-income rural US region.
Int J Qual Stud Health Well-being. 2016; 11:30396 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
Social networks influence health behavior and health status. Within social networks, "key players" often influence those around them, particularly in traditionally underserved areas like the Appalachian region in the USA. From a total sample of 787 Appalachian residents, we identified and interviewed 10 key players in complex networks, asking them what comprises a key player, their role in their network and community, and ideas to overcome and increase colorectal cancer (CRC) screening. Key players emphasized their communication skills, resourcefulness, and special occupational and educational status in the community. Barriers to CRC screening included negative perceptions of the colonoscopy screening procedure, discomfort with the medical system, and misinformed perspectives on screening. Ideas to improve screening focused on increasing awareness of women's susceptibility to CRC, providing information on different screening tests, improving access, and the key role of health-care providers and key players themselves. We provide recommendations to leverage these vital community resources.

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