1.
Discovery of common and rare genetic risk variants for colorectal cancer.
Huyghe, JR, Bien, SA, Harrison, TA, Kang, HM, Chen, S, Schmit, SL, Conti, DV, Qu, C, Jeon, J, Edlund, CK, et al
Nature genetics. 2019;(1):76-87
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Abstract
To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
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Food, microbiome and colorectal cancer.
Niederreiter, L, Adolph, TE, Tilg, H
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2018;(7):647-652
Abstract
You are what you eat. This adage has been confirmed by many studies demonstrating the high impact of nutrition on risk of cardiovascular diseases, many malignancies and other diseases. Dietary factors are of major relevance in the evolution of colorectal carcinoma. Various aspects are involved in colorectal carcinoma pathogenesis including genetics, lifestyle, age, chronic inflammation and others. It has only recently been recognized that the gut microbiota might reflect an important missing link in the interaction between diet and subsequent colorectal carcinoma development. Dietary factors are a major confounding factor affecting the composition of the intestinal microbiota. Several preclinical and clinical studies have recently suggested a role for the intestinal microbiota in potentially initiating and driving colorectal carcinoma. Therefore it is increasingly acknowledged that dietary factors might favor carcinogenesis via manipulation of the gut microbiota via potential outgrowth of certain bacterial populations, such as Fusobacterium nucleatum, Escherichia coli or Bacteroides fragilis. Excitingly, recent large clinical studies also highlighted a role for the gut microbiota and in particular Akkermansia muciniphila in tumor response toward chemotherapeutic agents and immune checkpoint inhibitors. This review will concentrate on the role of dietary factors in affecting the microbiota and implications in colorectal carcinoma.
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[Early versus traditional postoperative oral feeding in patients undergoing elective colorectal surgery: a meta-analysis of safety and efficacy].
Zhang, K, Cheng, S, Zhu, Q, Han, Z
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery. 2017;(9):1060-1066
Abstract
OBJECTIVE To compare the outcomes of early oral feeding (EOF) and the traditional oral feeding (TOF) in postoperative patients with colorectal cancer using Meta-analysis. METHODS The databases of PubMed, SCI, Ovid, The Cochrane Library, CNKI, CBM, VIP and Wanfang Data were searched to collect randomized controlled trial (RCT) about EOF versus TOF in patients undergoing elective colorectal surgery. The retrieval time span was from inception to June 1, 2016. The studies were screened according to the inclusion and exclusion criteria. The data were extracted and the quality was evaluated by 2 reviewers independently. The Meta-analysis was conducted using RevMan 5.2 software. RESULTS A total of 14 studies with 1 807 patients (906 cases in EOF group and 901 cases in TOF group) were included. The time to first passage of flatus (MD=-16.11 h, 95%CI:-18.27 to -13.94 h, P=0.00), postoperative hospital stay (MD=-1.92 d, 95%CI:-2.83 to -1.01 d, P=0.00), hospitalization cost (ten thousand yuan) (MD=-0.58, 95%CI:-0.71 to -0.46, P=0.00) were less in EOF group compared to TOF group. EOF patients had lower total complication rate (OR=0.68, 95%CI:0.48 to 0.95, P=0.03), in which the pulmonary infection (OR=0.27, 95%CI:0.13 to 0.53, P=0.00), pharyngolaryngitis (OR=0.06, 95%CI:0.04 to 0.11, P=0.00) were lower than those in TOF group, while the tube reinsertion (OR=2.34, 95%CI:1.08 to 5.07, P=0.03) was higher. The incidence of anastomotic leakage, nausea, vomiting, abdominal distension, diarrhea, and wound infection between two groups was not significantly different(all P>0.05). There was no significant difference between two groups in IgM (P>0.05), while the IgA (MD=0.3, 95%CI:0.12 to 0.48, P=0.00), IgG (MD=2.13 ,95%CI:0.82 to 3.44, P=0.001), CD4+ (MD=3.80, 95%CI:2.55 to 5.04, P=0.00), CD4+/CD8+ (MD=0.22, 95%CI:0.04 to 0.41, P=0.02) in EOF group were higher than those in TOF group. Postoperative CRP decreased rapidly in EOF group (MD=-30.10, 95%CI:-48.07 to -12.13, P=0.00), and IL-6 was not significantly different (P>0.05). EOF patients had higher serum albumin level 5 days after operation (MD=3.27, 95%CI: 2.48 to 4.07, P=0.00). CONCLUSIONS EOF can promote gas passage and defecation, reduce postoperative hospital stay and treatment costs. Also, it can decrease the incidence of complications and postoperative inflammation, and maintain immune function.
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Gut microbiota and colorectal cancer: insights into pathogenesis for novel therapeutic strategies.
Kang, Y, Pan, W, Cai, Y
Zeitschrift fur Gastroenterologie. 2017;(9):872-880
Abstract
Colorectal cancer (CRC), as a leading cause of cancer-related death, is triggered by the complex interplay of host genetics and environmental factors. Mounting evidence has shed light on the association of the gut microbiota dysbiosis with CRC. In CRC experimental models, certain gut microbial strains have been shown to inhibit or attenuate immune responses, indicating that specific species among intestinal commensal bacteria may play either a pathogenic or a protective role in the development of CRC. Oral intake of probiotics/prebiotics can therefore serve as a therapeutic approach for CRC treatment. Microbiota studies in cancer, however, are still at the early stage, lack of quantitative data for clinic application. Fortunately, sequencing-based technologies are a boon to further investigation on the association of the intestinal bacterial flora and human diseases. This review considers the evidence for the role of the gut microbiota in CRC development and progression, responsiveness to immune system, and the related therapeutic applications of probiotics/prebiotics.