Polymorphisms in the Angiogenesis-Related Genes EFNB2 , MMP2 and JAG1 Are Associated with Survival of Colorectal Cancer Patients

• Published in: International journal of molecular sciences Vol. 21; no. 15; p. 5395
• Main Authors: Scherer, Dominique, Deutelmoser, Heike, Balavarca, Yesilda, Toth, Reka, Habermann, Nina, Buck, Katharina, Kap, Elisabeth Johanna, Botma, Akke, Seibold, Petra, Jansen, Lina, Lorenzo Bermejo, Justo, Weigl, Korbinian, Benner, Axel, Hoffmeister, Michael, Ulrich, Alexis, Brenner, Hermann, Burwinkel, Barbara, Chang-Claude, Jenny, Ulrich, Cornelia M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.07.2020; MDPI
• Subjects: Adenocarcinoma - diagnosis; Adenocarcinoma - genetics; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Aged; Aged, 80 and over; Angiogenesis; Case-Control Studies; Chemotherapy; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - genetics; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Confidence intervals; Ephrin-B2 - genetics; Female; Gelatinase A; Gene Expression Regulation, Neoplastic; Genes; Genetic diversity; Genomes; Genotype; Health care; Humans; Jagged-1 Protein - genetics; Kinases; Ligands; Male; Marking; Matrix Metalloproteinase 2 - genetics; Medical prognosis; Middle Aged; Neovascularization, Pathologic - diagnosis; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - mortality; Neovascularization, Pathologic - pathology; Nucleotides; Odds Ratio; Polymorphism, Single Nucleotide; Population studies; Prognosis; Proportional Hazards Models; Risk; Risk Factors; Signal Transduction; Single-nucleotide polymorphism; Statistical analysis; Statistical models; Survival; Tumors; Vascular endothelial growth factor; colorectal cancer; single nucleotide polymorphism; angiogenesis; survival
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21155395

An individual's inherited genetic variation may contribute to the 'angiogenic switch', which is essential for blood supply and tumor growth of microscopic and macroscopic tumors. Polymorphisms in angiogenesis-related genes potentially predispose to colorectal cancer (CRC) or affect the survival of CRC patients. We investigated the association of 392 single nucleotide polymorphisms (SNPs) in 33 angiogenesis-related genes with CRC risk and survival of CRC patients in 1754 CRC cases and 1781 healthy controls within DACHS (Darmkrebs: Chancen der Verhütung durch Screening), a German population-based case-control study. Odds ratios and 95% confidence intervals (CI) were estimated from unconditional logistic regression to test for genetic associations with CRC risk. The Cox proportional hazard model was used to estimate hazard ratios (HR) and 95% CIs for survival. Multiple testing was adjusted for by a false discovery rate. No variant was associated with CRC risk. Variants in , and were significantly associated with overall survival. The association of the tagging SNP rs9520090 ( < 0.0001) was confirmed in two validation datasets ( -values: 0.01 and 0.05). The associations of the tagging SNPs rs6040062 in ( -value 0.0003) and rs2241145 in ( -value 0.0005) showed the same direction of association with overall survival in the first and second validation sets, respectively, although they did not reach significance ( -values: 0.09 and 0.25, respectively). , and are known for their functional role in angiogenesis and the present study points to novel evidence for the impact of angiogenesis-related genetic variants on the CRC outcome.