Abstract
BackgroundThe 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.MethodsPatients 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.ResultsOf 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.ConclusionsPatients 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.
Highlights
The prognosis of colorectal cancer (CRC) patients can be influenced by genetic mutations and nutritional status
Subjects with high microsatellite instability (MSI) tumors have a favorable prognosis in comparison with age and patients at matched stage with stable tumors in microsatellite stability (MS). [3, 7] Cavagnari et al BMC Cancer (2019) 19:644 patients with mutated KRAS and BRAF tumors have a worse prognosis compared to patients harboring wild type KRAS and BRAF. [3, 8]
[12] The available evidence indicates the importance of genetic information associated with the nutritional status of patients with CRC, there are few related studies as well as studies of gene and body composition variables. [13,14,15] Morikawa et al [14] verified the association of TP53 gene and body mass index (BMI) in patients with CRC
Summary
The prognosis of colorectal cancer (CRC) patients can be influenced by genetic mutations and nutritional status. The relationship between these variables is unclear. Microsatellite stability (MS) is frequently observed in obese individuals with CRC, with consequent reduction in the presence of mutations This condition may be related to several factors, including the high levels of cytokines that accompany obesity. These contradictory findings suggest a potential obesity paradox, preventing a conclusive interpretation of its role in predicting overall cancer survival Molecular changes, such as the presence of mutations, present clearer evidence regarding the prognosis of colon and rectum adenocarcinoma. The authors concluded that the survival of CRC patients with mutations in TP53 differs significantly according to their BMI. [14] This occurs because the tumor suppressor gene is induced in a cellular response to the reduction of nutrients or energy levels, avoiding cell proliferation under nutrient deprivation conditions. [16]
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