Risk of gastric cancer is associated with the MUC1 568 A/G polymorphism

Abstract

Abstract. Identifying the genetic variants that alter MUC1 protein expression may further our understanding of the risk for development of gastric cancer (GC). We used PCR-SSPs to identify the genotype of MUC1 A/G polymorphism at its 568 site of exon 2 and immunohistochemistry to detect MUC1 protein expression in GC patients and non-cancer subjects and analyzed the association between this polymorphism and MUC1 protein expression. We found that the frequency of AA genotype was significantly high in the GC patients and the risk for GC in AA genotype carriers increased 1.81-fold. Moreover, we found a significant underexpression of MUC1 protein in GC as compared to non-cancer subjects, which was negatively correlated to AA genotype of MUC1 (r=-0.1790, P=0.004). Furthermore, this study provides a possible mechanistic insight that the MUC1 A/G polymorphism at its 568 site disrupts the physiological functions of MUC1 which is important to the physiological protection of gastric mucosa. Thus we have provided evidence that may identify the MUC1 A/G polymorphism at 568 site, as a potential genetic factor which leads to an increase in susceptibility for GC through alteration of MUC1 gene and MUC1 expression in the population that carry the A allele.

Human papillomavirus type 18 oncoproteins exert their oncogenicity in esophageal and tongue squamous cell carcinoma cell lines distinctly

“…It is known that HPV18 oncoproteins can exert their oncogenic properties through targeting AKT [29], extracellular signal-regulated kinase (ERK) [30] and metalloprotease (MMP) [31, 32] pathways in cervical cancer cells, leading to cell survival, proliferation and metastasis. To date, the involvement of HPV18 oncoproteins in perturbing these pathways in esophageal and tongue SCC cell lines has not been clearly defined.…”

“…HPV-positive cells require HPV oncoproteins to survive and proliferate, which can occur through perturbation of signaling pathways, including AKT [29], ERK [30], suppression of the caspase cascade [42, 43], and MMPs for migration [31, 32]. AKT is known to possess a pro-survival role [41, 47], while ERK1/2 appears to be a dual-faced protein: anti- or pro-apoptotic kinase [48].…”

“…Whilst E7 downregulates retinoblastoma protein (pRB) and its related pocket proteins, including p130 and p107 [25–27], leading to transactivation of E2F response promoter genes [28]. In addition, HPV oncoproteins can deregulate AKT [29], ERK [30] and metalloproteases (MMPs) [31, 32], leading to cancer formation and progression. All these are classical molecular targets of HPV oncoproteins in cervical cancer.…”

Family-based exome sequencing combined with linkage analyses identifies rare susceptibility variants of MUC4 for gastric cancer

“…Two recent meta-analysis studies have shown that the G allele of MUC1 rs4072037 is associated with a decreased risk of GC [38,39]. MUC1 rs4072037 affects the gene promoter, leading to reduced transcriptional activity and MUC1 [40,41].…”

Association of Inflammation-Related Gene Polymorphisms With Susceptibility and Radiotherapy Sensitivity in Head and Neck Squamous Cell Carcinoma Patients in Northeast China

“…Genomic DNA was extracted from peripheral blood samples obtained from the study participants using the phenol-cholesterol method according to a standard procedure (45). The Matrix-Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF) genotyping system was used to genotype 612 individuals for 28 inflammation-related gene polymorphisms.…”