• Bacteria
• Biopsy
• Colorectum
• Dysbiosis
• Polyp

Colorectal cancer (CRC) remains one of the leading causes of mortality from malignant diseases worldwide. In general terms, CRC presents high heterogeneity due to the influence of different genetic and environmental factors; also, the neoplastic cells are strongly influenced by the extracellular matrix and several surrounding cells, known together as the tumor microenvironment (TME). Bidirectional communication takes place between the tumor and the TME through the release of autocrine and paracrine factors. Parathyroid hormone-related peptide (PTHrP) is a cytokine secreted by a wide variety of tissues and is able to regulate several cellular functions both in physiological as well as in pathological processes. It exerts its effects as a paracrine/autocrine factor, although its mode of action is mainly paracrine. It has been shown that this peptide is expressed by several tumors and that the tumor secretion of PTHrP is responsible for the malignant humoral hypercalcemia. Eight years ago, when our research group started studying PTHrP effects in the experimental models derived from intestinal tumors, the literature available at the time addressing the effects of PTHrP on colorectal tumors was limited, and no articles had been published regarding to the paracrine action of PTHrP in CRC cells. Based on this and on our previous findings regarding the role of PTH in CRC cells, our purpose in recent years has been to explore the role of PTHrP in CRC. We analyzed the behavior of CRC cells treated with exogenous PTHrP, focalizing in the study of the following events: Survival, cell cycle progression and proliferation, migration, chemoresistance, tumor-associated angiogenesis, epithelial to mesenchymal transition program and other events also associated with invasion, such us the induction of cancer stem cells features. This work summarizes the major findings obtained by our investigation group using in vitro and in vivo CRC models that evidence the participation of PTHrP in the acquisition of an aggressive phenotype of CRC cells and the molecular mechanisms involved in these processes. Recently, we found that this cytokine induces this malignant behavior not only by its direct action on these intestinal cells but also through its influence on cells derived from TME, promoting a communication between CRC cells and surrounding cells that contributes to the molecular and morphological changes observed in CRC cells. These investigations establish the basis for our next studies in order to address the clinical applicability of our findings. Recognizing the factors and mechanisms that promote invasion in CRC cells, evasion to the cytotoxic effects of current CRC therapies and thus metastasis is decisive for the identification of new markers with the potential to improve early diagnosis and/or to predict prognosis, to predetermine drug resistance and to provide treatment guidelines that include targeted therapies for this disease.

• Parathyroid hormone-related protein
• Colorectal cancer
• Tumor biomarkers
• Neoplastic processes
• Drug resistance
• Tumor microenvironment

• Colorectal Neoplasms
• Epithelial-Mesenchymal Transition
• Humans
• Hypercalcemia
• Parathyroid Hormone
• Parathyroid Hormone-Related Protein
• Phenotype
• Tumor Microenvironment

• Adenoma
• Colonoscopia
• Colonoscopy
• Colorectal cancer
• Cáncer colorrectal
• Hyperplastic polyps
• Polipectomía
• Polypectomy
• Pólipos hiperplásicos

• Hyperplastic polyp
• Levels
• Serial sections
• Sessile serrated adenoma/polyp
• Sessile serrated lesion

There are several studies with inconsistent conclusions regarding the association between the rs1801133 and rs1801131 polymorphisms within the MTHFR (methylenetetrahydrofolate reductase) gene and colorectal polyp risk. This discrepancy led us to assess the genetic impact of the two polymorphisms on the susceptibility to colorectal polyps.

A meta-analysis was carried out for quantitative synthesis. According to the inclusion/exclusion criteria, we retrieved, screened and selected all published articles related to colorectal polyps and the MTHFR rs1801133 and rs1801131 polymorphisms. The P value of association test, RRs (risk ratios) and 95% CIs (confidence intervals) were mainly produced.

A total of twenty-three case-control studies were included from twenty-two eligible articles. Pooling the results of both rs1801133 and rs1801131 polymorphisms in the overall population suggested a nonsignificant association between colorectal polyp cases and controls, in that all P values in the test of association were larger than 0.05. Nevertheless, pooling results in the “UK” subgroup of rs1801131, comprising five studies (1257 cases/1407 controls), indicated an elevated risk in colorectal polyp cases in comparison with controls, under the genetic models of CC vs. AA (P = 0.032, RR = 1.27, 95% CIs = 1.02, 1.57) and CC vs. AA+AC (P = 0.036, RR = 1.27, 95% CIs = 1.02, 1.60).

The C/C genotype of MTHFR rs1801131 is more likely to be a genetic risk factor for colorectal polyps in the UK region, although this finding should be verified with a larger sample size.

The online version of this article (10.1186/s12881-019-0822-y) contains supplementary material, which is available to authorized users.

• Colorectal polyps
• MTHFR
• Polymorphism
• Susceptibility

• China
• Colorectal Neoplasms
• Community Health Services
• Early Detection of Cancer
• Humans

Several studies have reported an association between levels of folate, homocysteine, and vitamin B₁₂ and the risk of colorectal polyps. Here, our aim is to examine the possible effect of folate, homocysteine, and vitamin B₁₂ levels on the risk of colorectal polyps by means of meta-analysis based quantitative synthesis. According to our inclusion/exclusion criteria, a total of 13 case–control studies were enrolled. The P-value of the association test, standard mean difference (SMD), and 95% confidence interval (CI) were calculated. Pooled analysis data showed a negative correlation between the risk of colorectal polyps and the levels of serum folate, red blood cell (RBC) folate, or vitamin B₁₂ (all P>0.05). Nevertheless, for homocysteine level, we also observed a statistically significant difference between cases and controls in the overall and subgroup analysis of hospital-based control (HB), population-based control (PB), Chinese, Caucasian, or Asian (all P<0.05, SMD > 0). We found that increased levels of homocysteine may be statistically and significantly related to the risk of colorectal polyps.

• colorectal polyps
• folate
• homocysteine
• vitamin B12

• heterochrony hepatic metastasis
• microRNA hsa-let-7e-5p
• next-generation sequencing
• rectal carcinoma