Background Colorectal cancer (CRC) and inflammatory bowel disease (IBD) are the most prevalent diseases of the digestive system, and their association is unequivocal. A long-standing inflammatory process is one of the causes of sporadic as well as inherited cancers as it impacts on malignant transformation in a wide variety of neoplastic diseases, including colorectal cancer. Methods An extensive publication search was performed in Medline and PubMed database. The keywords: colorectal carcinoma, inflammation, Crohn disease, ulcerative colitis and inflammatory bowel disease were used. Results The nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and toll like receptor (TLR) signaling pathways are clearly involved in the inflammatory process and are therefore implicated in the transformation of normal colonic mucosa to premalignant and malignant disease. Focal sites of inflammation could significantly increase the risk of initiation and development of cancer. Altered inflammatory activity is likely to be a result of either a disturbance of intestinal bacterial flora or an inadequate cellular response to it. Additionally, increasing the level of inflammation-related factors may also interfere with the control of cellular proliferation. Conclusions This review shows an overview of the genetic and environmental factors that appear to influence both the occurrence of IBD and CRC with particular reference to NOD2 and TLRs as well as pro- and anti-inflammatory cytokines associated with tumor initiation and progression (encompassing both tumor invasion and metastases), as they constitute potential targets for therapeutic intervention.

BackgroundDifferentiated thyroid carcinoma (DTC) originates from thyroid follicular epithelial cells and belongs to a group of slowly progressing tumors with a relatively good prognosis. However, recurrences and metastases are a serious problem in advanced stages. Furthermore, progression from a well differentiated thyroid carcinoma to an aggressive anaplastic one is possible.The majority of differentiated thyroid carcinomas are sporadic but a few alleles increasing the cancer risk are known. One of them is the c.470 T > C (p.I157T, rs17879961) missense substitution in the CHEK2 gene.Aim of the studyThe aim of this study was to investigate whether this specific CHEK2 alteration, c.470 T > C, predisposes the Great Poland (Wielkopolska) population to thyroid cancer.Methods602 differentiated thyroid carcinoma patients and 829 controls randomly selected from population were genotyped for the presence of the c.470C allele using pyrosequencing. Hardy-Weinberg Equilibrium (HWE) was tested for both groups by chi-square distribution and Fisher’s exact test. The odds ratios (ORs), 95% confidence intervals (CIs), and p-values were calculated using the R software.ResultsThe results of genotyping showed the presence of the c.470C allele in 51 patients with a frequency of 4.49%, while in a controls in 42 patients with a frequency of 2.53%. We demonstrated that in the Great Poland population the c.470C CHEK2 variant increases the risk of developing differentiated thyroid cancer almost twice (OR = 1.81, p = 0.004). The risk of papillary thyroid carcinoma in female patients homozygous for the c.470C allele was shown to increase almost 13-fold (OR = 12.81, p = 0.019).ConclusionsIdentification of c.470C CHEK2 gene variant ought to be taken into account by healthcare policymakers. Future well-designed and larger population studies are of great value in confirming these findings. Moreover, a combination of genetic factors together with environmental exposures should also be considered.Electronic supplementary materialThe online version of this article (doi:10.1186/s13053-015-0030-5) contains supplementary material, which is available to authorized users.

The cannabinoid receptor type 1 (CB1R), a G protein-coupled receptor (GPCR), plays an essential role in the control of many physiological processes such as hunger, memory loss, gastrointestinal activity, catalepsy, fear, depression, and chronic pain. Therefore, it is an attractive target for drug discovery to manage pain, neurodegenerative disorders, obesity, and substance abuse. However, the psychoactive adverse effects, generated by CB1R activation in the brain, limit the use of the orthosteric CB1R ligands as drugs. The discovery of CB1R allosteric modulators during the last decade provided new tools to target the CB1R. Moreover, application of the site-directed mutagenesis in combination with advanced physical methods, especially X-ray crystallography and computational modeling, has opened new horizons for understanding the complexity of the structure, function, and activity of cannabinoid receptors. In this paper, we present the latest advances in research on the CB1R, its allosteric modulation and allosteric ligands, and their translational potential. We focused on structural essentials of the cannabinoid 1 receptor- ligand (drug) interactions, as well as modes of CB1R signaling regulation.