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

作者：Dominique Scherer, Heike Deutelmoser, Yesilda Balavarca, Réka Tóth, Nina Habermann, Katharina Buck, Elisabeth J. Kap, Akke Botma, Petra Seibold, Lina Jansen, Justo Lorenzo Bermejo, Korbinian Weigl, Axel Benner, Michael Hoffmeister, Alexis Ulrich, Hermann Brenner, Barbara Burwinkel, Jenny Chang‐Claude, Cornelia M. Ulrich · 发表于：International Journal of Molecular Sciences · 年份：2020 · DOI：10.3390/ijms21155395 · 被引用次数：17 · 研究领域：Cancer, Hypoxia, and Metabolism、Ubiquitin and proteasome pathways、Ferroptosis and cancer prognosis

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 EFNB2, MMP2 and JAG1 were significantly associated with overall survival. The association of the EFNB2 tagging SNP rs9520090 (p < 0.0001) was confirmed in two validation datasets (p-values: 0.01 and 0.05). The associations of the tagging SNPs rs6040062 in JAG1 (p-value 0.0003) and rs2241145 in MMP2 (p-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 (p-values: 0.09 and 0.25, respectivel...