title: Is the ABCB1 gene associated with the increased risk of gastric cancer development?--preliminary research.
abstract: One of the most common malignant diseases, both worldwide and in Poland, is gastric cancer. The pathogenesis of gastric cancer development is not entirely clear. Next to the environmental risk factors, such as Helicobacter pylori infection or dietary habits, the host genetic factors as predispositions to gastric cancer development are discussed. A transmembrane protein that could be associated with predisposition to cancer development is P-glycoprotein (P-gp). Physiologically, P-gp is present in normal tissue of the gastrointestinal tract, where it plays a protective role by transporting xenobiotics from a cell into extracellular environment. P-gp is encoded by the highly polymorphic ABCB1 gene. The most frequent polymorphisms at positions 1236, 2677, and 3435 may affect both the function and amount of protein, thereby leading to a loss of its physiological function, which could increase the predisposition to development of many diseases, including cancer. In this study, the potential significance of the ABCB1 gene in the development and progression of gastric cancer was evaluated. In 19 tissue samples collected from patients with gastric cancer, the ABCB1 gene polymorphisms were identified at positions 1236 and 2677 by automated sequencing and SNP 3435 by the RFLP method. The relative level of ABCB1 expression was measured in 10 samples of gastric cancer and morphologically normal tissues by real-time PCR. For SNPs at positions 1236, 2677, and 3435, no statistically significant differences in genotype frequencies between gastric cancer patients and healthy individuals were found. However, genotype TT for all studied polymorphisms occurred more frequently in the group of gastric cancer patients (31.6, 26.3, 42.1%, respectively) than in the group of healthy individuals (14.6, 13.5, 21.9%, respectively). The lowest relative expression levels of ABCB1 mRNA were observed for genotypes CC of SNP 1236, CC of SNP 3435, and GG of SNP 2677 (median: 0.215, 0.160, 0.160, respectively). There was a tendency that mutant homozygote TT for SNPs at positions 1236, 2677, and 3435 occurred more frequently in the subgroup of patients with Tis or stage I of TNM classification (SNP 1236 p = 0.0760; SNP 2677 p = 0.0813; SNP 3435 p = 0.0760) than in the subgroup of patients with stage II or III. Also the expression levels were lowest (median 0.740) in the group of patients with the less advanced clinical stage of cancer (Tis or I). Preliminary research showed that the ABCB1 gene polymorphisms at positions 1236, 2677, and 3435 were not related to an increased susceptibility of gastric cancer development. However, they may be associated with the inhibition of gastric cancer progression.
authors.affiliation: Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Interdepartmental Chair of Laboratory and Molecular Diagnostics, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland. Electronic address: marta.zebrowska@umed.lodz.pl.
authors.forename: M
authors.initials: M
authors.lastname: Zebrowska
authors.affiliation: Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Interdepartmental Chair of Laboratory and Molecular Diagnostics, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Salagacka
authors.affiliation: Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Interdepartmental Chair of Laboratory and Molecular Diagnostics, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Jelen
authors.affiliation: Department of Pathology, Chair of Oncology, Medical University of Lodz, Pomorska 251,92-213 Lodz, Poland.
authors.forename: D
authors.initials: D
authors.lastname: Jesionek-Kupnicka
authors.affiliation: Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Interdepartmental Chair of Laboratory and Molecular Diagnostics, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Mirowski
authors.affiliation: Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Interdepartmental Chair of Laboratory and Molecular Diagnostics, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Balcerczak
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D065840:Protective Factors; D012333:RNA, Messenger / Q000032:analysis; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D014408:Biomarkers, Tumor; D012333:RNA, Messenger
keywords: ABCB1; Expression; Gastric cancer; Polymorphism