ABSTRACT. The objective of this study was to examine the association between TNF-α serum levels and -308G>A and -238G>A polymorphisms in the corresponding gene by comparing healthy subjects to colorectal cancer (CRC) patients from a Mexican population. Serum levels of TNF-α were found to significantly differ between CRC patients and controls (P = 0.001), but no relationship between the -308G>A and -238G>A polymorphisms and increased CRC risk was established (P > 0.05). However, an association between the -308G>A variant and disease became evident when the distribution of AA-GA genotypes was examined in patients with hematologic toxicity (neutropenia) and those without (odds ratio = 3.356, 95% confidence interval = 1.295-8.698, P = 0.013). The GG haplotype was more common in controls than CRC patients, with a frequency of 0.85 among the former, but this difference was not significant (P > 0.05). In conclusion, TNF-α serum levels and AA-AG genotypes of the TNF-α -308G>A polymorphism may significantly contribute to CRC susceptibility in the population examined in this investigation.

TYMS 2R3R polymorphism and the -[IVS]14+1G>A mutation in DPYD was not associated with susceptibility to CRC. However, the 2R/2R and 2R/3R genotypes of TYMS polymorphism could significantly contribute to hematological and gastric toxicity in CRC patients in this sample population.

Resumen Mundialmente, el cáncer colorrectal representa la tercera causa de muerte en hombres y la segunda causa de muerte en mujeres, con cerca de 1.2 millones de casos nuevos diagnosticados y 600,000 muertes estimadas. Una proporción importante de pacientes son diagnosticados con enfermedad metastásica al momento del diagnóstico. La neoangiogénesis es la formación de nuevos vasos sanguíneos a partir de los existentes, los cuales juegan un papel importante en la progresión y crecimiento tumoral. Se han identificado factores relacionados con el crecimiento endotelial, entre ellos el factor de crecimiento endotelial vascular. Diversos estudios han demostrado la participación en el desarrollo angiogénico tumoral de la activación de los sistemas de la coagulación y fibrinólisis. Algunos de estos factores son el factor von Willebrand, el fibrinógeno, el activador del plasminógeno de tipo I, su inhibidor y su receptor, además del dímero D y las plaquetas. Se considera que las concentraciones séricas de estas proteínas son factores predictivos de respuesta al tratamiento, progresión de la enfermedad y superviviencia. La interacción entre las células tumorales, la angiogénesis y la activación de la coagulación es una retroalimentación positiva. Las estrategias que interfieran en esta relación pueden prevenir o tratar el cáncer, como el uso de quimioterapia en combinación con nuevos agentes específicos de diana. Además, el papel de los anticoagulantes o antiplaquetarios en el tratamiento del cán-cer aún no se ha determinado. (creativecommons.org/licenses/by-nc-nd/4.0/). Abstract Worldwide, colorectal cancer is the third cause of death in men and the second leading cause of death in women, with about 1.2 million new cases diagnosed and 600,000 estimated deaths. A significant proportion of patients are diagnosed with metastatic disease at diagnosis. Angiogenesis is the formation of new blood vessels from existing ones, which play an important role in tumor growth and progression. Factors related to endothelial growth, including vascular endothelial growth factor, have been identified. Several studies have shown the PALABRAS CLAVEAngiogénesis; Cáncer colorrectal; Estado protrombótico; Pronóstico; Trombosis; Factor de crecimiento endotelial vascular (VEGF)

Worldwide, colorectal cancer is the third cause of death in men and the second cause of death in women, with nearly 1.2 million newly-diagnosed cases and 600,000 estimated deaths. A significant proportion of patients have metastatic disease at diagnosis. Neoangiogenesis is the formation of new blood vessels from those already existing, which play an important role in tumor growth and progression. Factors related to endothelial growth have been identified including vascular endothelial growth factor. Different studies have demonstrated coagulation and fibrinolysis systems activation participation in tumor angiogenic development. Some of these factors are Von Willebrand factor, fibrinogen, type I plasminogen activator inhibitor and receptor, in addition to D-dimer and platelets. Serum concentrations of these proteins are considered to be predictors of treatment response, disease progression and survival. Interaction between tumor cells, angiogenesis and coagulation activation is a positive feedback, and strategies interfering in this relationship, such as the use of chemotherapy in combination with new specifically targeted agents, can prevent or treat cancer. In addition, the role of anticoagulant or antiplatelet agents in the treatment of cancer has not yet been determined. (creativecommons.org/licenses/by-nc-nd/4.0/).