TRAILR1 may play an important role during cell death signaling either as an endogenous factor in the regulation of cancer cells. TRAILR1 consists of two extracellular cysteine-rich, ligand-binding pseudorepeats (50s and 90s loops), one single transmembrane helix as well as the apoptosis-triggering cytoplasmic death domain. Some data indicate that normal variations within the sequence of apoptotic genes may lead to suboptimal apoptotic capacity and therefore increased cancer risk. TRAILR1 polymorphisms have been described in different human cancer, such as breast cancer, gastric cancer, bladder cancer, lung cancer and endometriosis . Polymorphism in the ectodomain of TRAILR1 C626G (rs4871857), A683C (rs17088993) and A1322G (rs2230229) were found in a higher frequency in primary cancers of different origin as compared to matched controls. The C626G in the ectodomain region of DR4, whereas A683C in extracellular cycteine-rich domain and A1322G in the death domain of TRAILR1.
Chen W, Tang W R, Zhang M, et al. Association of DR4 (TRAIL-R1) polymorphisms with cancer risk in Caucasians: an updated meta-analysis[J]. Asian Pac J Cancer Prev, 2014, 15: 2889-92.