Impact of genetic mutations and nutritional status on the survival of patients with colorectal cancer.

BACKGROUND: The prognosis of colorectal cancer (CRC) patients can be influenced by genetic mutations and nutritional status. The relationship between these variables is unclear. The objective of the study was to verify the variables involved in the nutritional status and genetic mutations, which correlate with survival of CRC patients. METHODS: Patients with surgical intervention for tumor resection were evaluated using body mass index, nutritional screening, patient self-produced global subjective assessment, phase angle, and computed tomography to calculate the areas of visceral adipose tissue (VAT) and subcutaneous adipose tissue, and muscle mass for the determination of sarcopenia. Ten gene mutations involved in CRC carcinogenesis were studied (PIK3CA, KRAS, BRAF, EGFR, NRAS, TP53, APC, PTEN, SMAD4, and FBXW7). DNA was extracted from fresh tumor or paraffin tissues. RESULTS: Of the 46 patients, 29 (64.4%) were at nutritional risk and 21 (45.7%) were moderately malnourished. However, there was a high percentage of VAT in 24 (61.5%) and sarcopenia in 19 (48.7%) patients. These variables were associated with a higher risk of mortality. Nutritional risk, moderate or severe malnutrition, phase angle < 5°, VAT < 163.8 cm2 in men and <  80.1 cm2 in women, and sarcopenia were associated with the relative risk of death, with respective hazard ratios/odds ratios and 95% confidence intervals of 8.77 (1.14-67.1), 3.95 (1.11-14.0), 3.79 (1.10-13.1), 3.43 (1.03-11.4), and 3.95 (1.06-14.6). Increased VAT was associated with a lower risk of death, even in patients older than 60 years or those harboring mutated KRAS. CONCLUSIONS: Patients with positive indicators for malnutrition or risk of malnutrition had an increased risk of death. No relationship was identified between the presence of mutations and survival.

Effects of Grape Juice in Superoxide Dismutase and Catalase in Colorectal Cancer Carcinogenesis Induced by Azoxymethane

Background: The intestinal mucosa is commonly exposed to oxidant nutrients and carcinogens, which can lead to the generation of free radicals. The antioxidants present in the diet assume great importance as possible protective agents, reducing the oxidative damage. In this way, we evaluated the antioxidant action of grape juice on preneoplastic lesions induced by azoxymethane (AOM) in Wistar rats. Methods: The colorectal carcinogenesis was induced by two intraperitoneal injections of 15mg/kg of AOM in Wistar rats. The animals were divided in 7 groups and treated with 1 and 2% concentrations of grape juice before and after carcinogen administration. After euthanasia, the expression of antioxidant enzymes catalase (CAT), copper-zinc superoxide dismutase (Cu/Zn-SOD) and manganese superoxide dismutase (Mn-SOD) CAT, SOD1 and SOD2 were evaluated by immunohistochemistry. Results: AOM decreased the expression of CAT and Mn-SOD enzymes, but not for Cu/Zn-SOD. We observed an increase expression of CAT and Mn-SOD after grape juice administration in some concentrations according to the time of administration of the grape juice before the carcinogen or just after the carcinogen. Conclusion: Our results suggest an independent action of each enzyme and a possible antioxidant action of the grape juice components in the diet being able to balance the body to neutralize the superoxide radicals and not leave them in the cell-damaging form.