Detection of genetic alterations in gastric cancer patients from Saudi Arabia using comparative genomic hybridization (CGH).

BACKGROUND: The present study was conducted to discover genetic imbalances such as DNA copy number variations (CNVs) associated with gastric cancer (GC) and to examine their association with different genes involved in the process of gastric carcinogenesis in Saudi population. METHODS: Formalin-fixed paraffin-embedded (FFPE) tissues samples from 33 gastric cancer patients and 15 normal gastric samples were collected. Early and late stages GC samples were genotyped and CNVs were assessed by using Illumina HumanOmni1-Quad v.1.0 BeadChip. RESULTS: Copy number gains were more frequent than losses throughout all GC samples compared to normal tissue samples. The mean number of the altered chromosome per case was 64 for gains and 40 for losses, and the median aberration length was 679115bp for gains and 375889bp for losses. We identified 7 high copy gain, 52 gains, 14 losses, 32 homozygous losses, and 10 copy neutral LOHs (loss of heterozygosities). Copy number gains were frequently detected at 1p36.32, 1q12, 1q22, 2p11.1, 4q23-q25, 5p12-p11, 6p21.33, 9q12-q21.11, 12q11-q12, 14q32.33, 16p13.3, 17p13.1, 17q25.3, 19q13.32, and losses at 1p36.23, 1p36.32, 1p32.1, 1q44, 3q25.2, 6p22.1, 6p21.33, 8p11.22, 10q22.1, 12p11.22, 14q32.12 and 16q24.2. We also identified 2 monosomy at chromosome 14 and 22, 52 partially trisomy and 22 whole chromosome 4 neutral loss of heterozygosities at 13q14.2-q21.33, 5p15.2-p15.1, 5q11.2-q13.2, 5q33.1-q34 and 3p14.2-q13.12. Furthermore, 11 gains and 2 losses at 1p36.32 were detected for 11 different GC samples and this region has not been reported before in other populations. Statistical analysis confirms significant association of H. pylori infection with T4 stage of GC as compare to control and other stages. CONCLUSIONS: We found that high frequency of copy number gains and losses at 1p36.23, 1p32.1, 1p36.32, 3q25.2, 6p21.33 and 16q24.2 may be common events in gastric cancer. While novel CNVs at 1p36.32 harbouring PRDM16, TP73 and TP73-AS1 genes showed 11 gains and 2 losses for 11 different GC cases and this region is not reported yet in Database of Genomic Variants may be specific to Saudi population.

Role of Chlamydia pneumoniae, helicobacter pylori and cytomegalovirus in coronary artery disease.

Coronary artery disease (CAD) is the leading cause of death in many countries. The underlying mechanism of the chronic inflammatory process in atherosclerosis is still unknown. As a possible trigger, different viruses and bacteria may be associated with atherosclerotic diseases. The aim of this work was to investigate the association of chronic infection with C pneumoniae, H pylori and cytomegalovirus (CMV) infections and CAD. Fifty patients [20 with acute coronary artery disease (ACAD) and 30 with chronic coronary artery disease (CCAD)] in addition to 15 healthy individuals as a control group were involved in this study. The studied individuals were subjected to complete history taking, thorough physical examination, electrocardiography, echocardiography and coronary angiography (for patients). Assessment of blood glucose level, lipid profile and creatine kinase (CK) was performed. Determination of hsCRP was done by nephlemetry, while C pneumoniae-, H pylori- and CMV-specific IgG antibodies was done by enzyme immunoassay. Results showed that the levels of cholesterol, triglycerides, LDL-c and hsCRP were significantly higher, while HDL-c was significantly lower among patients compared to that of the controls. A significantly (P<0.05) higher perecentage of patients had C pneumoniae and H pylori-specific IgG antibodies as compared to that of the controls. Higher percentage of patients had CMV-specific IgG antibody, however, there was no significant difference between the 2 groups. The levels of C pneumoniae and H pylori-specific IgG antibodies were significantly (P<0.001) higher among patients with CAD when compared to that of the controls. CMV-specific IgG level in patients was higher compared to that of the controls, however, the difference was not statistically significant. Among acute CAD patients, C pneumoniae-specific IgG was positively correlated with hsCRP (P<0.05), cholesterol (p<0.01) and HDL-c (P<0.05), while H pylori-specific IgG was positively correlated with triglyceride level (P<0.05). Among patients with CCAD, hsCRP was negatively correlated with HDL-c (P<0.05). There was no significant correlation between the levels of CMV-specific IgG and lipid profile or hsCRP. In conclusion, the level of C pneumoniae and H pylori-specific IgG antibodies are elevated among CAD patients and their presence was associated with development of the disease. They were significantly correlated to cholesterol level. Moreover, C pneumoniae-specific IgG was significantly correlated with hsCRP among ACAD patients, suggesting an important role of these organisms in the development of CAD by altering lipid profile and induction of inflammation.