Fecal Genetic Mutations and Human DNA in Colorectal Cancer and Polyps Patients.

BACKGROUND: Colorectal cancer (CRC) is one of the most frequent cancers. Genetic mutations in CRC already described can be detected in feces. Microarray methods in feces can represent a new diagnostic tool for CRC and significant improvement at public health. AIM: to analyze stool DNA by human DNA quantify and microarray methods as alternatives to CRC screening. METHOD: Three methods were analyzed in stool samples: Human DNA Quantify, RanplexCRC and KRAS/BRAF/PIK3CA (KBP) Arrays. RESULTS: KBP array mutations were presented in 60.7% of CRC patients and RanplexCRC Array mutations in 61.1% of CRC patients. Sensitivity and specificity for human DNA quantification was 66% and 82% respectively. Fecal KBP Array had 35% sensitivity and 96% specificity and RanplexCRC Array method had 78% sensitivity and 100% specificity. CONCLUSION: Microarray methods showed promise as potential biomarkers for CRC screening; however, these methods had to be optimized to improve accuracy and applicability by clinical routine.

Association Between Nutrition Status and Survival in Elderly Patients With Colorectal Cancer.

BACKGROUND: Aging patients with cancer have a higher risk of mortality and treatment-associated morbidity than younger patients. Nutrition status may play an important role in cancer mortality. We aimed to evaluate the survival time of elderly patients with colorectal cancer and its association with body mass index (BMI), the patient-generated subjective global assessment (PG-SGA), and phase angle (PA). MATERIALS AND METHODS: BMI, PG-SGA, and PA were determined for all patients (n = 250) at first assessment. RESULTS: Seventy-one (28.4%) patients were in active oncologic treatment (group 1) and 179 (71.6%) were in remission (group 2). At the time of the analysis, 73 (29.2%) patients had died and 177 (70.8%) were censored. The mean (standard deviation) age was 70.9 (7.49) years; 17.2% were undernourished, 56% normal weight, and 26.8% were overweight. According to the PG-SGA, 35.2% of patients needed some nutrition intervention and 4.4% needed it urgently. The mean PA was 4.94 ± 1°. PG-SGA, tumor stage, and PA differed significantly ( P < .001) between the groups; BMI did not ( P = .459). Severe malnutrition (PG-SGA C), compared with PG-SGA A, was associated with a relative hazard of death of 12.04 (95% confidence interval [CI], 3.43-42.19, P < .001). PA >5° was associated with better prognosis: a relative hazard of 0.456 (95% CI, 0.263-0.792; P < .005). CONCLUSION: Among elderly patients with colorectal cancer, PA and PG-SGA were prognosis factors. PA >5° was associated with best survival and PG-SGA C with worst survival.

Genetic polymorphisms of vitamin D metabolism genes and serum level of vitamin D in colorectal cancer.

BACKGROUND: The metabolism of vitamin D is complex, its receptor (VDR) and proteins encoded by the genes CYP27B2 and CYP24A1 can influence vitamin D serum levels. The aim of this study was to investigate the relationship of the polymorphisms of VDR (ApaI and BsmI), CYP27B1 and CYP24A1 with serum vitamin D levels in both forms, 25(OH)D3 (circulating form) and 1,25(OH)2D3 (active form), in colorectal cancer (CRC) patients. METHODS: One hundred fifty-two CRC patients and 321 controls were included. DNA was extracted from peripheral blood. Polymorphisms of BsmI and ApaI were identified by PCR-RFLP. Those of CYP24A1 (rs6013897, rs158552 and rs17217119) and CYP27B1 (rs10877012) were determined by gene sequencing. RESULTS: The median serum levels of circulating vitamin D were not different between CRC patients and controls; however, the percentage of those with deficient vitamin D was higher in patients with cancer. The active form of the vitamin D was higher in CRC patients. VDR, CYP27B1 and CYP24A1 polymorphic genotypes had no influence on serum levels of circulating vitamin D. The correlation between circulating and active vitamin D forms was lower among patients with CRC, regardless of the presence or absence of any genetic polymorphism. The mean serum levels of active vitamin D were higher among patients with polymorphic genotype variants of Apa1 or Bsm1. CONCLUSIONS: CRC patients had a higher frequence of insufficient vitamin D and a higher concentration of active vitamin D. These concentration were higher between patients with polymorphic genotypes variants of ApaI and BsmI, CYP24A1 and CYP27B1. Polymorphic genotypes cause a lower correlation between the forms of vitamin D.

O uso da bioimpedância elétrica e do ângulo de fase na avaliação do estado nutricional de pacientes com câncer: uma revisão integrativa / The use of electrical bioimpedance and the phase angle in the evaluation the nutritional status of patients with cancer: an integrative review

Contexto: Pacientes com câncer podem apresentar involução do estado nutricional devido a alterações metabólicas determinadas pela doença e ao tratamento, e a avaliação nutricional pode identificar precocemente a desnutrição e permitir intervenção adequada. O uso da bioimpedância elétrica tem crescido nos últimos anos, uma vez que a obtenção do ângulo de fase tem demonstrado ser bom indicador do estado nutricional. Objetivo: Apresentar e discutir os resultados de estudos que utilizaram o ângulo de fase na avaliação do estado nutricional de pacientes com câncer. Métodos: Estudo de revisão integrativa da literatura, no qual foi realizado o levantamento de artigos científicos nas bases de dados Cochrane, PubMed, LILACS (Literatura Latino-Americana e do Caribe em Ciências da Saúde) e Korea Med. Resultados: A busca resultou em 86 artigos, sendo selecionadas 21 publicações. Destes, 38,1% estudaram mais de um tipo de câncer, sendo cabeça e pescoço (19,1%) o tipo mais avaliado, e 61,9% avaliaram a sobrevida em relação aos valores do ângulo de fase. A observação da redução nos valores do ângulo de fase foi relacionada à sobrevida, ao estado nutricional e ao estadiamento. Conclusão: A bioimpedância elétrica para a avaliação do ângulo de fase é um procedimento rápido, de baixo custo e não invasivo. É importante considerar que outros estudos com a utilização da bioimpedância sejam conduzidos, a fim de confirmar sua confiabilidade como marcador de estado nutricional na prática clínica.

The influence of nutritional status and disease on adiponectin and TNF-α; levels in colorectal cancer patients.

BACKGROUND: The aim of this study was to evaluate the association between adiponectin and tumor necrosis factor-α;(TNF-α;) serum levels in colorectal cancer (CRC) patients and compare these levels to clinical stage and nutritional status. METHODS: A total of 79 patients were enrolled in the study (39 with CRC and 40 in the control). Nutritional status was assessed by Patient-Generated Subjective Global Assessment (PG-SGA), body mass index (BMI), and phase angle (PhA). Adiponectin and TNF-α;serum concentrations were determined using an enzyme-linked immunosorbent assay. RESULTS: Serum adiponectin levels were higher among CRC patients (p = 0.001). TNF-α;serum levels were not significantly different between the groups, but patients with stage III or IV CRC had higher levels of TNF-α;than those with lower stage disease (p = 0.037). The three tools used for the assessment of nutritional status (BMI, PhA, and PG-SGA) demonstrated that patients with a more severe nutritional deficit had higher adipocytokine levels, although these differences were significant only to TNF- , when distributed PhA in tertiles. CONCLUSIONS: Adiponectin levels were higher among CRC patients. Although TNF-α;serum levels from CRC patients did not differ significantly to the control group, CRC patients with stage III or IV had higher levels compared to those with stage I and II tumors. Nutritional status, as determined by BMI, PhA, and PG-SGA, demonstrated that patients with a greatest nutritional deficit, had higher levels of adipocytokines; however, these differences were significant only for TNF-, when distributed PhA in tertiles.

ANTECEDENTES: El propósito de este estudio fue evaluar la asociación entre las concentraciones séricas de adiponectina y de factor de necrosis tumoral-(TNF-) en paciente con cáncer colorrectal (CCR) y comparar estas concentraciones con el estadio clínico y el estado nutritivo. MÉTODOS: Se reclutó a un total de 79 pacientes en el estudio (39 con CCR y 40 en el grupo control). Se evaluó el estado nutritivo mediante la Evaluación Global Subjetiva Generada por el Paciente (PG-SGA), el índice de masa corporal (IMC) y el ángulo de fase (AF). Se determinaron las concentraciones séricas de adiponectina y de TNF-mediante un inmunoensayo de absorción ligado a enzima. RESULTADOS: Las concentraciones séricas de adiponectina fueron superiores en los pacientes con CCR (p = 0,001). Las concentraciones séricas de TNF-no fueron significativamente distintas entre los grupos pero los pacientes con CC en estadios III o IV tuvieron mayores concentraciones de TNF-que aquellos con un menor estadio de la enfermedad (p = 0,037). Las tres herramientas empleadas para evaluar el estado nutritivo (IMC, AF y PG­SGA) demostraron que los pacientes con un déficit nutricional más pronunciado presentaban mayores concentraciones de adipocitocina, aunque algunas diferencias sólo fueron significativas para el TNF-cuanto se distribuyó el AF en terciles. CONCLUSIONES: Las concentraciones de adiponectina fueron superiores en pacientes con CCR. Aunque las concentraciones séricas de TNF-de los pacientes con CCR no diferían significativamente de las del grupo control, los pacientes con CCR en estadios III o IV tuvieron concentraciones superiores en comparación con aquellos con tumores en estadios I y II. El estado nutritivo, determinado por IMC, AF y PG-SGA, demostró que los pacientes con un mayor déficit nutricional tenían concentraciones superiores de adipocitocinas; sin embargo, estas diferencias sólo fueron significativas para el TNF-cuando el AF se distribuyó en terciles.

Immunoexpression of galectin-3 in colorectal cancer and its relationship with survival.

INTRODUCTION: Galectin-3 is an endogenous galactose-binding protein that is expressed in a wide range of normal and neoplasic tissues and is thought to be involved in cellular adhesion, growth regulation, and apoptosis. Galectin-3 seems to have an important role in colorectal cancer. The aim of this study was to evaluate the immunoexpression of galectin-3 in patients with colorectal cancer under surgery and chemotherapy treatment and the relationship of galectin-3 expression and clinical aspects or tumor evolution. PATIENTS AND METHODS: Galectin-3 expression was examined immunohistochemically in 75 samples of colorectal tissues. A scoring system was used to evaluate the cytoplasmic cells color. Among the patients, 40 were female; the average age was 61.98 years old. According to the site, 42.6% was of the rectum, 33.4% right colon, and 24% left colon. Thirty-three tumors were stage II, 32 stage III, and ten stage IV. RESULTS AND DISCUSSION: Galectin-3 immunoexpression was classified as 1 in 57.33% of tumors. The highest percentage of staining cells appeared in the most advanced cancer (p = 0.4899). Patients with recurrence had a great number of tumors with high score (p = 0.0465). In addition, high or moderate galectin-3 immunoexpression had been associated with an increased marginal risk for death (p = 0.0795). The immunoexpression of galectin-3 was strong or moderate in 42% of the colorectal tumors. Patients with strong or moderate immunoexpression of galectin-3 died or had recurrence more frequently. The risk of death was marginally reduced in patients with negative or low-grade galectin-3. Galectin-3 cytoplasmatic immunoexpression seems to be a prognostic factor in colorectal cancer because a higher risk of recurrence had been observed in tumors with a high score of galectin-3. However, a higher risk of death was not found on this group.

A snapshot of current genetic testing practice in Lynch syndrome: The results of a representative survey of 33 Latin American existing centres/registries

We aimed to assess the current genetics practice to manage patients with Lynch syndrome (LS) across Latin America. A Latin American LS survey was sent out to 52 centres/registries, comprising a total of 12 countries from the region. Overall, 33 centres completed the survey, of which the oldest LS registry was established in 1992 in Sao Paulo (Brazil), and the youngest this year in San Jose (Costa Rica). In total, 87% (26/30) of the participating centres/registries belonging to the nine countries are performing genetic testing. Overall, 1352 suspected families were sequenced. Pathogenic variants were identified in 34% of the families, with slightly differing distribution of variants between females and males. Path_MLH1 variants were identified in 39% of females and 50% of males (p = 0.023), while path_MSH2 were identified in 37% of females and males, followed by path_PMS2 in 11% of females and 8% of males, path_MSH6 in 13% of females and 3% of males (p < 0.001) and path_EPCAM in 0.3% of females and 2% of males. In Latin America, 9 of 12 (75%) participating countries had implemented healthcare for LS. LS screening is inconsistently applied within Latin America healthcare systems because of structural differences in the healthcare systems between the countries(AU)

P53 Arg72Pro polymorphism in gastric cancer patients.

INTRODUCTION: Polymorphism in codon 72, exon 4 of p53 may alter apoptosis and cancer progression. PATIENTS AND METHODS: P53 Arg72Pro genotype was assessed by PCR from 84 gastric cancer patients and 185 controls. The control group was comparable in sex, race, age, smoking, and alcohol intake to the cancer group. RESULTS AND DISCUSSION: There was no difference among the frequency of the alleles or genotypes between the groups. P53 Pro/Pro was associated to a lower risk of metastatic disease (p = 0.02) but not to lymph nodes metastasis or worst prognosis. Arg/Arg or Arg/Pro genotype may be associated to metastatic disease.

From colorectal cancer pattern to the characterization of individuals at risk: Picture for genetic research in Latin America

Colorectal cancer (CRC) is one of the most common cancers in Latin America and the Caribbean, with the highest rates reported for Uruguay, Brazil and Argentina. We provide a global snapshot of the CRC patterns, how screening is performed, and compared/contrasted to the genetic profile of Lynch syndrome (LS) in the region. From the literature, we find that only nine (20%) of the Latin America and the Caribbean countries have developed guidelines for early detection of CRC, and also with a low adherence. We describe a genetic profile of LS, including a total of 2,685 suspected families, where confirmed LS ranged from 8% in Uruguay and Argentina to 60% in Peru. Among confirmed LS, path_MLH1 variants were most commonly identified in Peru (82%), Mexico (80%), Chile (60%), and path_MSH2/EPCAM variants were most frequently identified in Colombia (80%) and Argentina (47%). Path_MSH6 and path_PMS2 variants were less common, but they showed important presence in Brazil (15%) and Chile (10%), respectively. Important differences exist at identifying LS families in Latin American countries, where the spectrum of path_MLH1 and path_MSH2 variants are those most frequently identified. Our findings have an impact on the evaluation of the patients and their relatives at risk for LS, derived from the gene affected. Although the awareness of hereditary cancer and genetic testing has improved in the last decade, it is remains deficient, with 39%-80% of the families not being identified for LS among those who actually met both the clinical criteria for LS and showed MMR deficiency(AU)