Abnormal bowel movement frequency increases the risk of rectal cancer : Evidence from cohort studies with one million people.
排便频率异常增加直肠癌风险: 来自 100万人队列研究的证据。
- 作者列表："Shen L","Li C","Li N","Shen L","Li Z
:Previous studies from case-control studies failed to draw reliable conclusions regarding the relationship between bowel movement frequency and the risk of colorectal cancer. To further examine this relationship, we collect the data from cohort studies data make a more accurate estimation. Several online data were searched from inception to February 29, 2020. Ten cohort studies involving 1,038,598 individuals were included in our study. The pooled results indicated that a bowel movement of less than once per day was not associated with the risk of colorectal cancer (relative risk (RR)=1.00, 95% confidence interval (CI): 0.87-1.16, P=0.950) compared with that of once per day. Compared with a bowel movement frequency of once per day, a bowel movement of more than once per day was also not related to elevated risk of colorectal cancer (RR=1.04, 95% CI: 0.91-1.19, P=0.570). The subgroup analyses indicated a low or high bowel movement frequency did not increase the risk of colon cancer (RR=0.91, 95% CI: 0.80-1.03, P=0.130). However, an increased frequency of bowel movements increased the risk of rectal cancer (RR=1.34, 95% CI: 1.19-1.52, P<0.001). The sensitivity analysis still supports the results. Bo significant publication bias existed. The data from cohort indicated that less bowel movement frequency was not associated with the risk of colorectal cancer. The frequency of bowel movement affects the risk of rectal cancer.
: 以前来自病例对照研究的研究未能得出关于排便频率与结直肠癌风险之间关系的可靠结论。为了进一步检验这种关系，我们从队列研究数据中收集数据，做出更准确的估计。从开始到 2020年2月29日，搜索了几个在线数据。我们的研究包括 10 项队列研究，涉及 1,038,598 例个体。汇总结果表明，每天排便少于一次与结直肠癌风险无关 (相对风险 (RR)= 1.00，95% 置信区间 (CI): 0.87-1.16，P = 0.950) 与每天 1 次相比。与每天排便一次的频率相比，每天排便一次以上也与结直肠癌风险升高无关 (RR = 1.04，95% CI: 0.91-1.19，P = 0.570)。亚组分析表明，低或高排便频率不增加结肠癌的风险 (RR = 0.91，95% CI: 0.80-1.03，P = 0.130)。然而，排便频率增加增加直肠癌的风险 (RR = 1.34，95% CI: 1.19-1.52，P<0.001)。灵敏度分析仍然支持结果。Bo 存在显著的发表偏倚。来自队列的数据表明，较少的排便频率与结直肠癌的风险无关。排便的频率影响直肠癌的风险。
METHODS::Aims: Radiotherapy is predominantly used as one of the treatment modalities to treat local tumor in colorectal cancer (CRC). Hindrance in disease treatment can be attributed to radio-tolerance of cancer stem cells (CSCs) subsistence in the tumor. Understanding the radio-resistant property of CSCs might help in the accomplishment of targeted radiotherapy treatment and increased disease-free survival. Telomeric RAP1 contributes in modulation of various transcription factors leading to aberrant cell proliferation and tumor cell migration. Therefore, we investigated the role of RAP1 in maintaining resistance phenotype and acquired stemness in radio-resistant cells.Main Methods: Characterization of HCT116 derived radio-resistant cell (HCT116RR) was performed by cell survival and DNA damage profiling. RAP1 silenced cells were investigated for DNA damage and expression of CSC markers through western blotting and Real-time PCR post-irradiation. Molecular docking and co-immunoprecipitation study were performed to investigate RAP1 and KLF4 interaction followed by RAP1 protein status profiling in CRC patient.Key findings: We established radio-resistant cells, which showed tolerance to radiotherapy and elevated expression of CSC markers along with RAP1. RAP1 silencing showed enhanced DNA damage and reduced expression of CSC markers post-irradiation. We observed strong physical interaction between RAP1 and KLF4 protein. Furthermore, higher RAP1 expression was observed in the tumor of CRC patients. Dataset analysis also revealed that high expression of RAP1 expression is associated with poor prognosis.Significance: We conclude that higher expression ofRAP1 implicates its possible role in promoting radio-resistance in CRC cells by modulating DNA damage and CSC phenotype.
METHODS::Cancer stem-like cells are rare immortal cells within tumor, which are thought to play important roles in ionizing radiation (IR) therapy-resistance. Quercetin is a natural flavonoid with potential anti-cancer properties without significant cytotoxicity in normal tissues. In this study, we demonstrated that quercetin-IR combination treatment exhibited more dramatic anti-cancer effect than either quercetin or IR treatment alone via targeting colon cancer stem cells (CSCs) and inhibiting the Notch-1 signaling. These effects were further verified by in vivo studies which showed remarkable decrease of the CSCs markers and the expression of Notch-1 signaling proteins in human colon cancer xenografts in nude mice. Co-treatment with quercetin and low dose of radiation significantly reduced the expressions of all five proteins of γ-secretase complex in HT-29 and DLD-1 cells. In addition, ectopic expression of the Notch intracellular domain (NICD) partly reversed the inhibition effects by the combination therapy. In conclusion, our results indicated that the combination of quercetin (20 μM) and IR (5Gy) might be a promising therapeutic strategy for colon cancer treatment by targeting colon cancer stem-like cells and inhibiting the Notch-1 signaling. In future studies, we intend to further explore the potential therapeutic efficacy of the quercetin-radiation combination treatment in clinical trials.
METHODS:OBJECTIVES:Long-term prevention of metastatic disease remains a challenge in locally advanced rectal cancer, and robust pretreatment prognostic factors for metastatic progression are lacking. We hypothesized that detecting circulating tumor-specific DNA (ctDNA) based on hypermethylation of the neuropeptide Y gene (meth-ctDNA) could be a prognostic marker in the neoadjuvant setting; we examined this in a secondary, explorative analysis of a prospective trial. MATERIALS AND METHODS:Serum samples were prospectively collected in a phase III trial for locally advanced rectal cancer. Positivity for and fractional abundance of meth-ctDNA in baseline samples were estimated. Overall survival (OS) and the rate of distant metastases were compared between meth-ctDNA positive and negative patients; other prognostic factors were controlled for in multivariate Cox regression. Importance of quantitative load was examined by considering the fractional abundance of meth-ctDNA relative to total circulating DNA. RESULTS:Baseline serum samples were available for 146 patients. In total, 30 patients had presence of meth-ctDNA, with no correlation with cT (P=0.8) or cN (P=0.6) stages. Median follow-up was 10.6 years for OS and 5.1 years for freedom from distant metastases. Patients with meth-ctDNA had significantly worse 5-year OS (47% vs. 69%), even when controlling for other prognostic factors (hazard ratio=2.08; 95% confidence interval, 1.23-1.51). This seemed mainly driven by disparity in the rate of distant metastases (55% vs. 72% at 5 y, P=0.01); hazard ratio=2.20 (95% confidence interval, 1.19-4.07, P=0.01) in multivariate analysis. Increased quantitative load was highly significant for worse outcomes. CONCLUSIONS:Meth-ctDNA could be a potential prognostic marker in the neoadjuvant setting and may, if validated, identify patients at increased risk of distant metastases.