Low selenium (Se) status correlates with increased risk of colorectal cancer (CRC). Since Se exerts its biological roles through the selenoproteins, genetic variations in selenoprotein genes may influence susceptibility to CRC. This study analysed 12 single-nucleotide polymorphisms (SNPs) in selenoprotein genes [glutathione peroxidase 1 (GPX1), GPX4, 15 kDa selenoprotein (SEP15), selenoprotein S (SELS), selenoprotein P (SEPP1) and thioredoxin reductase 2 (TXNRD2)] and in genes that code for a key protein in Se incorporation [SECIS-binding protein 2 (SBP2)] and in antioxidant defence [superoxide dismutase 2 (SOD2)] in relation to sporadic CRC incidence. CRC patients (832) and controls (705) from the Czech Republic were genotyped using allele specific PCR. Logistic regression analysis showed that three SNPs were significantly associated with an altered risk of CRC: rs7579 (SEPP1), rs713041 (GPX4) and rs34713741 (SELS). The association of these SNPs with disease risk remained after data stratification for diagnosis and adjustments for lifestyle factors and sex. Significant two-loci interactions were observed between rs4880 (SOD2), rs713041 (GPX4) and rs960531 (TXNRD2) and between SEPP1 and either SEP15 or GPX4. The results indicate that SNPs in SEPP1, GPX4 and SELS influence risk of CRC. We hypothesize that the two-loci interactions reflect functional interactions between the gene products. We propose that these variants play a role in cancer development and represent potential biomarkers of CRC risk.

ABCA12, ABCA13, ABCC1, ABCC8 and ABCD2 present potential modifiers of progression and response to the chemotherapy of breast carcinoma.

Esophageal and gastric cancers represent tumors with poor prognosis. Unfortunately, radiotherapy, chemotherapy, and targeted therapy have made only limited progress in recent years in improving the generally disappointing outcome. Immunotherapy with checkpoint inhibitors is a novel treatment approach that quickly entered clinical practice in malignant melanoma and renal cell cancer, but the role in esophageal and gastric cancer is still poorly defined. The principal prognostic/predictive biomarkers for immunotherapy efficacy currently considered are PD-L1 expression along with defects in mismatch repair genes resulting in microsatellite instability (MSI-H) phenotype. The new molecular classification of gastric cancer also takes these factors into consideration. Available reports regarding PD-1, PD-L1, PD-L2 expression and MSI status in gastric and esophageal cancer are reviewed to summarize the clinical prognostic and predictive role together with potential clinical implications. The most important recently published clinical trials evaluating checkpoint inhibitor efficacy in these tumors are also summarized.

The comprehensive approach for the lipidomic characterization of human breast cancer and surrounding normal tissues is based on hydrophilic interaction liquid chromatography (HILIC)-electrospray ionization mass spectrometry (ESI-MS) quantitation of polar lipid classes of total lipid extracts followed by multivariate data analysis using unsupervised principal component analysis (PCA) and supervised orthogonal partial least square (OPLS). This analytical methodology is applied for the detailed lipidomic characterization of ten patients with the goal to find the statistically relevant differences between tumor and normal tissues. This strategy is selected for better visualization of differences, because the breast cancer tissue is compared with the surrounding healthy tissue of the same patient, therefore changes in the lipidome are caused predominantly by the tumor growth. A large increase of total concentrations for several lipid classes is observed, including phosphatidylinositols, phosphatidylethanolamines, phosphatidylcholines, and lysophosphatidylcholines. Concentrations of individual lipid species inside the abovementioned classes are also changed, and in some cases, these differences are statistically significant. PCA and OPLS analyses enable a clear differentiation of tumor and normal tissues based on changes of their lipidome. A notable decrease of relative abundances of ether and vinylether (plasmalogen) lipid species is detected for phosphatidylethanolamines, but no difference is apparent for phosphatidylcholines.