An assessment of gastric cancer associated factors and strategies for early case detection in patients seen at the university teaching hospital in Lusaka, Zambia.

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Kayamba, Violet Jolezya
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The University of Zambia
ABSTRACT Gastric cancer is one of the leading causes of cancer related mortality globally. It carries a very poor prognosis with a one-year survival rate of less than 15%. The main objective of this study was to investigate environmental, biological and dietary factors associated with gastric cancer, and to explore the potential of using blood in gastric juice for detection of gastric mucosal lesions through pre-endoscopy screening. The study was conducted at the University Teaching Hospital, in Lusaka, Zambia. It was a case-control study of patients with histologically confirmed gastric adenocarcinoma (GA) or gastric premalignant (GP) lesions as cases, and those without either as controls. Questionnaires were used to collect data on basic characteristics and associated risk factors. Biological characteristics were measured in gastric juice, blood, urine, and gastric biopsies. This was done using enzyme-linked immunosorbent assay, high-performance liquid chromatography, immunofluorescence, in situ hybridisation, urine and pH test strips. A multiplex serological assay was used to quantify antibodies to thirteen immunogenic Helicobacter pylori proteins. Study data were analysed in STATA version 15 (College Station, TX, USA). Graphs were prepared in both STATA and Graphpad prism version 7. Included for analysis in this study were 388 patients, 92 (24%) of whom had gastric tumours seen during endoscopy. Results showed that gastric cancer had similar occurrence in both sexes (OR 1.1; 95% CI 0.5-1.9), and 18/92 (20%) of them were below the age of 45 years. GA disproportionately affected rural (OR 2.9; 95% CI 1.5-5.3) and poor (OR 4.2; 95% CI 1.9-9.1) people. The proportion of Epstein-Barr virus (EBV) associated GA was 11% by in situ hybridisation, and it was similar between HIV infected and uninfected patients (OR 1.5; 95% CI 0.02-22). Evidence of microsatellite instability using immunofluorescence for MutL homolog 1 was observed in 63% of GA. Patients regularly exposed to biomass smoke were more likely to have GA, (p=0.001) and to exhibit evidence of oxidative stress to DNA, (p=0.03). The odds of GA in patients with history of regular consumption of processed meat was 7.0; 95% CI 1.4-34. In patients taking green vegetables daily, the odds were 0.2; 95% CI 0.1-0.5. The median estimated 24-hour sodium excretion of 19 g (IQR 14-24 g) by the Tanaka method. Aflatoxin M1 was present in the urine of 61% of the patients, with a median; 18 ng/mg creatinine (IQR 1.7- 40) ng/mg creatinine, while 96% had ochratoxin A in their blood median; 0.1 ng/ml (IQR 0.2-0.6 ng/ml). Being Helicobacter pylori (H. pylori) seropositive (determined by the presence of at least four antibodies) was not associated with either GA (OR 1.1; 95% CI 0.5-3.3) or GP (OR 1.9; 95% CI 0.4-17.6). Antibodies to CagA (p=0.0007), VacA (p=0.0006), HcpC (p=0.0006) and Omp (p=0.03) were significantly higher in active gastric inflammation than in GA. Overall, there was no association between H. bilis or H. hepaticus seropositivity and GA or GP. Serological response to four EBV antigens was not associated with GA. The presence of blood in gastric juice was associated with gastric cancer (OR 6.7; 95% CI 2-35), with a case detection sensitivity of 91% and a specificity of 41% and an area under the receiver operating characteristic curve of 0.8; 95% CI 0.7-0.9. There was a high proportion of early onset and microsatellite unstable GA, disproportionately affecting poor rural residents. Of the infectious risk factors evaluated, H. pylori was only associated with active gastric inflammation, but not GA or GP. EBV was absent in most of the tumours and HIV showed no influence on gastric carcinogenesis. Environmental and dietary risk factors showed greater influence on GA than the infectious agents. Testing for blood in gastric juice had high sensitivity but low specificity for gastric cancer detection. Data from this thesis can be used to further analyse specific risk factors for each gastric cancer subtype and explore the pathophysiological mechanisms involved. Key words: gastric cancer, gastric premalignant lesions, risk factors, biomass smoke, mycotoxins, gastric juice,