Increased Oxidative Stress in Gastric Cancer Patients and Their First-Degree Relatives: A Prospective Study from Northeastern Brazil

Abstract

Background and aims: First-degree relatives of gastric cancer patients are at increased risk of developing gastric cancer. Increased oxidative stress, including lipid peroxidation, has been associated with gastric carcinogenesis. Whether first-degree relatives of gastric cancer patients have increased oxidative stress remains unknown. We aimed to compare oxidative stress in patients with gastric cancer, their first-degree relatives, and dyspeptic controls.

Methods: A total of 155 patients undergoing upper endoscopy were prospectively enrolled, including 50 with gastric cancer, 49 first-degree relatives of gastric cancer patients, and 56 controls. Serum concentrations of malondialdehyde (MDA) and glutathione) and activities of superoxide dismutase (SOD) and catalase were measured. Multivariate analysis adjusting for sex, age, smoking status, and alcohol consumption was performed.

Results: Lipid peroxidation, as measured by concentration of MDA (nmol/mL), was higher (p = 0.04), and glutathione levels were lower (p < 0.001) in the gastric cancer group compared to controls. There was no difference in the catalase activity among the groups. There was no difference in glutathione and MDA concentration or catalase activity between the different stages of gastric cancer based on the TNM classification. Relatives of gastric cancer patients had higher glutathione concentration (μmol/mL) compared to gastric cancer patients (262.5 vs. 144.6; p = 0.018), while there was no difference in MDA concentration. Catalase and superoxide dismutase activity were lower in the gastric cancer group (3.82 vs. 0.91; p < 0.001 and 1.04 vs. 0.6; p < 0.001) compared to their first-degree relatives. Interestingly, MDA concentration in the first-degree relative group was higher than in the control group (7.9 vs. 5.1; p = 0.03).

Conclusions: In this study, similarly to gastric cancer patients, their first-degree relatives were found to have increased oxidative stress compared to controls. Further studies are warranted to validate this observation and to better understand the role of oxidative stress as a possible biomarker in this population.

Figure 1

(a) Glutathione serum level (GSH) expressed in μmol/mL; (b) serum catalase activity (CAT) expressed nmol/min; (c) malondialdehyde serum level (MDA), expressed in nmol/mL; and (d) superoxide dismutase, expressed in nmol/mg of protein, of control patients, gastric cancer (GC), and relatives of gastric cancer patients. Detailed univariate and multivariate analysis with p values are available in Tables 2 and 4. ∗p < 0.05 compared to control; ^#p < 0.05 compared to relative of the GC group. ^§SOD activity in a subset of patients (control group, n = 31; gastric cancer group, n = 32; relatives gastric cancer, n = 49).