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1.
Gene-environment interactions and colorectal cancer risk: An umbrella review of systematic reviews and meta-analyses of observational studies.
Yang, T, Li, X, Montazeri, Z, Little, J, Farrington, SM, Ioannidis, JPA, Dunlop, MG, Campbell, H, Timofeeva, M, Theodoratou, E
International journal of cancer. 2019;(9):2315-2329
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Abstract
The cause of colorectal cancer (CRC) is multifactorial, involving both genetic variants and environmental risk factors. We systematically searched the MEDLINE, EMBASE, China National Knowledge Infrastructure (CNKI) and Wanfang databases from inception to December 2016, to identify systematic reviews and meta-analyses of observational studies that investigated gene-environment (G×E) interactions in CRC risk. Then, we critically evaluated the cumulative evidence for the G×E interactions using an extension of the Human Genome Epidemiology Network's Venice criteria. Overall, 15 articles reporting systematic reviews of observational studies on 89 G×E interactions, 20 articles reporting meta-analyses of candidate gene- or single-nucleotide polymorphism-based studies on 521 G×E interactions, and 8 articles reporting 33 genome-wide G×E interaction analyses were identified. On the basis of prior and observed scores, only the interaction between rs6983267 (8q24) and aspirin use was found to have a moderate overall credibility score as well as main genetic and environmental effects. Though 5 other interactions were also found to have moderate evidence, these interaction effects were tenuous due to the lack of main genetic effects and/or environmental effects. We did not find highly convincing evidence for any interactions, but several associations were found to have moderate strength of evidence. Our conclusions are based on application of the Venice criteria which were designed to provide a conservative assessment of G×E interactions and thus do not include an evaluation of biological plausibility of an observed joint effect.
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FOLFOXIRI plus biologics in advanced colorectal cancer.
García-Alfonso, P, Torres, G, García, G, Gallego, I, Ortega, L, Sandoval, C, Muñoz, A, Lloansí, A
Expert opinion on biological therapy. 2019;(5):411-422
Abstract
INTRODUCTION The combination of oxaliplatin, irinotecan, fluorouracil (5-FU), and leucovorin (FOLFOXIRI) results in improved outcomes compared with standard chemotherapy when used in frontline to treat patients with metastatic colorectal cancer (mCRC). FOLFOXIRI has been recently combined with biologic agents aiming further improvement in outcomes. AREAS COVERED This manuscript provides a comprehensive review of the results achieved by the FOLFOXIRI+biologic combination when used as first-line treatment in patients with mCRC. The search retrieved 19 clinical trial reports and 7 ongoing trials. The results are discussed focusing on secondary resection of metastatic disease, impact of sidedness (right-left primary tumor site), and impact of biomarkers. EXPERT OPINION Panitumumab is the only biologic that has proved its value when added to FOLFOXIRI in a randomized clinical trial. FOLFOXIRI-bevacizumab has the widest data from two large randomized phase III trials, being an option to be used in both the palliative and the conversion-therapy settings. However, the true benefit from adding bevacizumab remains to be established as it has not been evaluated in a randomized setting yet. Data on response rates and secondary resection rates are promising with the FOLFOXIRI-anti-EGFR combinations and may constitute a valuable option. Results of ongoing head-to-head studies will shed additional light on this issue.
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Understanding patient-reported outcome measures in colorectal cancer.
Besson, A, Deftereos, I, Chan, S, Faragher, IG, Kinsella, R, Yeung, JM
Future oncology (London, England). 2019;(10):1135-1146
Abstract
Quality of life has become increasingly regarded as a key outcome measurement for cancer patients. Patient-reported outcome measures (PROMs) represent the tools used to ascertain self-reported quality of life. This review provides a summary of the literature regarding the use of PROMs in colorectal cancer and evaluates the advantages and limitations of generic and disease specific questionnaires that can be utilized in clinical practice. Factors that influence PROMs are outlined, including cancer characteristics, patient factors and treatment methods. Finally, future directions for the use of PROMs in colorectal cancer to inform healthcare delivery at an individual- and systems-based level are discussed.
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Long noncoding RNA FEZF1-AS1 in human cancers.
Zhou, Y, Xu, S, Xia, H, Gao, Z, Huang, R, Tang, E, Jiang, X
Clinica chimica acta; international journal of clinical chemistry. 2019;:20-26
Abstract
Long noncoding RNAs (lncRNAs) have been shown to play key roles in various human tumors. Ectopic expression of the lncRNA FEZ finger zinc 1 antisense 1 (FEZF1-AS1) have been reported in different cancers, including colorectal cancer, gastric neoplasia, hepatocellular carcinoma and so on. Summarizing all literature correlated with FEZF1-AS1, it is obvious that FEZF1-AS1 is mainly involved in tumorigenesis and progression through competing endogenous RNA (ceRNA) which sponges tumor-suppressive microRNA (miRNA) and recruiting mechanism. Moreover, the aberrant expression of FEZF1-AS1 is related to clinical features of patients with cancers, and regulates cellular proliferation, anti-apoptosis, invasion and metastasis through diverse underlying mechanisms. The role of FEZF1-AS1 in carcinogenesis and progression suggests that it may be a potential diagnostic biomarker or a novel therapeutic target for cancers.
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[Effect of life style interventions over quality of life in colorectal cancer survivors].
Valenzuela Feris, S, Von Oetinger, A
Revista de gastroenterologia del Peru : organo oficial de la Sociedad de Gastroenterologia del Peru. 2019;(2):153-159
Abstract
INTRODUCTION One third of cancer deaths are related to poor diet, physical inactivity and obesity. The high healthcare costs of cancer treatment and its repercussions on the quality of life have led the scientific community to investigate a variety of other interventions. METHODS Review of experimental and observational studies of the last 5 years, including adult subjects surviving colorectal cancer, subjected to lifestyle interventions of a minimum duration of 12 weeks. The review was guided by the PRISMA statement (data extraction from PubMed, Science Direct and EBSCO Medline Complete). The selection of the studies was completed using the Covidence platform. RESULTS There are positive associations between physical activity level and quality of life; on the other hand, in survivors of colorectal cancer, inverse relationships between time of sedentary attitude and quality of life are evidenced. CONCLUSION Lifestyle interventions generate an increase in quality of life indicators in survivors of colorectal cancer.
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A Complex Role for Calcium Signaling in Colorectal Cancer Development and Progression.
Wang, W, Yu, S, Huang, S, Deng, R, Ding, Y, Wu, Y, Li, X, Wang, A, Wang, S, Chen, W, et al
Molecular cancer research : MCR. 2019;(11):2145-2153
Abstract
Clinical data suggest that many malignant cancers are associated with hypercalcemia. Hypercalcemia can facilitate the proliferation and metastasis of gastric and colon tumors, and has been considered a hallmark of end-stage disease. However, it has also been reported that dietary calcium or vitamin D supplementation could reduce the risk of many types of cancers. In particular, the intestines can absorb considerable amounts of calcium via Ca2+-permeable ion channels, and hypercalcemia is common in patients with colorectal cancer. Thus, this review considers the role of calcium signaling in the context of colorectal cancer and summarizes the functions of specific regulators of cellular calcium levels in the proliferation, invasion, metastasis, cell death, and drug resistance of colorectal cancer cells. The data reveal that even a slight upregulation of intracellular Ca2+ signaling can facilitate the onset and progression of colorectal cancer, while continuous Ca2+ influx and Ca2+ overload may cause tumor cell death. This dual function of Ca2+ signaling adds nuance to the debate over the hallmarks of colorectal cancer, and may even provide new directions and strategies for clinical interventions.
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Chemoprevention of colorectal cancer: Past, present, and future.
Umezawa, S, Higurashi, T, Komiya, Y, Arimoto, J, Horita, N, Kaneko, T, Iwasaki, M, Nakagama, H, Nakajima, A
Cancer science. 2019;(10):3018-3026
Abstract
Chemoprevention began to be considered as a potential strategy for lowering the incidence of cancer and cancer-related deaths in the 1970s. For clinical chemoprevention trials against cancer, including colorectal cancer (CRC), well-established biomarkers are necessary for use as reliable endpoints. Difficulty in establishing validated biomarkers has delayed the start of CRC chemoprevention development. Chemoprevention trials for CRC have only recently been initiated thanks to the identification of reliable biomarkers, such as colorectal adenomas and aberrant crypt foci. Some promising agents have been developed for the prevention of CRC. The chemopreventive effect of selective cyclooxygenase 2 inhibitors has been shown, although these inhibitors are associated with cardiovascular toxicity as a crucial adverse effect. Aspirin, which is a unique agent among non-steroidal anti-inflammatory drugs (NSAIDs) showing minimal gastrointestinal toxicity and no cardiovascular risk, has prevented adenoma recurrence in some randomized controlled trials. More recently, metformin, which is a first-line oral medicine for type 2 diabetes, has been shown to be safe and to prevent adenoma recurrence. A recommendation of the United States Preventive Services Task Force published in 2016 provides a Grade B recommendation for the use of aspirin for chronic prophylaxis against diseases, including CRC, in certain select populations. However, the roles of other agents have yet to be determined, and investigations to identify novel "post-aspirin" agents are also needed. The combined use of multiple drugs, such as aspirin and metformin, is another option that may lead not only to stronger CRC prevention, but also to improvement of other obesity-related diseases.
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Anthocyanins/anthocyanidins and colorectal cancer: What is behind the scenes?
de Sousa Moraes, LF, Sun, X, Peluzio, MDCG, Zhu, MJ
Critical reviews in food science and nutrition. 2019;(1):59-71
Abstract
Colorectal cancer (CRC) is one of the most common cause of cancer death. Phytochemicals, especially anthocyanins/anthocyanidins (A/A), have gathered attention of the scientific community owing to their anti-inflammatory, antioxidant, and cancer-inhibitory properties. In this review, we discussed the possible mechanisms whereby A/A exhibit intestinal anticarcinogenic characteristics. Anthocyanins/anthocyanidins inhibit the pro-inflammatory NF-κB pathway, attenuate Wnt signaling and suppress abnormal epithelial cell proliferation. In addition, A/A induce mitochondrial-mediated apoptosis and downregulate Akt/mTOR (mammalian target of rapamycin) pathway. Furthermore, activation of AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) also contributes to the anti-carcinogenic effects of A/A. Finally, downregulation of metalloproteinases (MMPs) by A/A inhibits tumor invasion and metastasis. In conclusion, A/A exert their anti-tumor effects against colorectal carcinogenesis via multiple mechanisms, providing insights into the use of A/A as a natural chemopreventive intervention on major colorectal carcinogenesis.
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Dietary Intakes of Calcium, Iron, Magnesium, and Potassium Elements and the Risk of Colorectal Cancer: a Meta-Analysis.
Meng, Y, Sun, J, Yu, J, Wang, C, Su, J
Biological trace element research. 2019;(2):325-335
Abstract
The purpose of this study was to analyze the existing studies and to investigate the relationship between the risk of colorectal cancer (CRC) and intakes of four individual dietary elements calcium (Ca), iron (Fe), magnesium (Mg), and potassium (K). All relevant articles in both Chinese and English were searched and collected from PubMed, Web of Science, and Chinese National Knowledge Infrastructure databases up to December 17, 2017. There were 29 eligible literatures selected for further meta-analysis, including 14 cohort studies and 15 case-control studies. The meta-analysis of cohort studies indicated that the high intakes of dietary Ca and Mg were negatively associated with the risk of CRC, as the hazard ratios (HR) were 0.76 (95% confidence interval (CI) 0.72, 0.80) and 0.80 (95% CI 0.73, 0.87), respectively. Nevertheless, high intake of dietary heme Fe was positively correlated to the incidence of colon cancer (HR = 1.01, 95% CI 0.82, 1.19) and rectal cancer (HR = 1.04, 95% CI 0.67, 1.42). A meta-analysis of case-control studies indicated that high intakes of dietary Ca, Mg, and K were negatively related with the occurrence of CRC, because the odds ratios (OR) were 0.36 (95% CI 0.32, 0.40), 0.80 (95% CI 0.63, 0.98) and 0.97 (95% CI 0.74, 1.21), respectively. However, high Fe intake from diet was positively correlated with the rising increasing of CRC (OR = 1.04, 95% CI 0.91, 1.18). More research is needed to indicate the risk relationship between element intake and CRC.
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A Review of the In Vivo Evidence Investigating the Role of Nitrite Exposure from Processed Meat Consumption in the Development of Colorectal Cancer.
Crowe, W, Elliott, CT, Green, BD
Nutrients. 2019;(11)
Abstract
The World Cancer Research Fund (WCRF) 2007 stated that the consumption of processed meat is a convincing cause of colorectal cancer (CRC), and therefore, the public should avoid it entirely. Sodium nitrite has emerged as a putative candidate responsible for the CRC-inducing effects of processed meats. Sodium nitrite is purported to prevent the growth of Clostridium botulinum and other food-spoiling bacteria, but recent, contradictory peer-reviewed evidence has emerged, leading to media reports questioning the necessity of nitrite addition. To date, eleven preclinical studies have investigated the effect of consuming nitrite/nitrite-containing meat on the development of CRC, but the results do not provide an overall consensus. A sizable number of human clinical studies have investigated the relationship between processed meat consumption and CRC risk with widely varying results. The unique approach of the present literature review was to include analysis that limited the human studies to those involving only nitrite-containing meat. The majority of these studies reported that nitrite-containing processed meat was associated with increased CRC risk. Nitrite consumption can lead to the formation of N-nitroso compounds (NOC), some of which are carcinogenic. Therefore, this focused perspective based on the current body of evidence links the consumption of meat containing nitrites and CRC risk.