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Introducción: La concentración e integridad del ADN libre circulante (ADN-lc) son biomarcadores de diagnóstico y pronóstico en múltiples padecimientos. Objetivo. Determinar la concentración e índice de integridad del ADN-lc en una muestra de población general de Jalisco, México. Método. Se analizaron muestras de sangre periférica de 117 personas procedentes de Jalisco. El ADN-lc se cuantificó mediante fluorometría Qubit 2.0 y amplificación por q-PCR de ALU115. El índice de integridad se determinó por la relación de los amplificados ALU247/ALU115. Resultados. La concentración media de ADN-lc mostró 294 ng/ml por fluorometría Qubit 2.0 y 108.08 ng/ml por q-PCR. El índice de integridad calculado por la relación ALU247/ALU115 fue 0.45. La concentración mostró diferencia significativa por edad, pero no por sexo. El índice de integridad no mostró diferencias significativas por edad ni sexo. Conclusiones. Existen amplias diferencias en ADN-lc entre los dos procedimientos aquí utilizados, así como comparado con otras poblaciones. Palabras claves: ADN libre circulante; Cell-Free DNA; ADN-lc; índice de integridad; población general.

Colorectal cancer (CRC) is the third most common cancer in the world. Overall survival is related to clinical stage: more advanced stages show lower survival rates; therefore, they need to be monitored regularly with new, less invasive and more specific biomarkers. The concentration and integrity index of circulating cell-free DNA (ccfDNA) have been proposed as potential diagnostic and prognostic biomarkers for CRC, however, inconsistent results are still observed in different reports. Here we analyze these potential CRC biomarkers in a Mexican population. In this study, 124 patients with sporadic CRC and 37 healthy individuals were examined as a reference group. The ccfDNA was isolated from plasma samples of all included subjects. The ccfDNA concentration was determined by fluorometry and the integrity index (ALU247/ALU115 ratio) by quantitative PCR amplification (qPCR) of ALU sequences. The results show that ccfDNA concentration was higher in CRC patients than in the reference group (P=0.001). The integrity index showed no significant differences between these groups (P=0.258), except for histological type (P=0.012). A higher ccfDNA concentration was also associated with patients younger than 50 years (P=0.030). The ccfDNA concentration showed significant discriminatory power (AUC: 0.854, C.I.: 0.78-0.92, P=0.001) between patients and the reference group and between tumor-node-metastasis (TNM) stages. In conclusion, ccfDNA concentration proves to be a good diagnostic biomarker for CRC patients, whereas the integrity index did not show diagnostic utility.

Colorectal cancer is the third cause of cancer and the second leading cause of death worldwide. The CD44 gene plays a key role in malignant processes, including growth, survival, epithelial to mesenchymal transition and metastasis. It is also known that some variants as rs187116 (c.67+4883G>A) and rs7116432 (c.2024+779A>G) can modulate the function of the CD44 gene and malignant transformation in several neoplasms. This study aims to explore, for the first time, the association of the CD44 rs187116 and rs7116432 variants in patients with colorectal cancer. Genomic DNA from 250 patients and 250 healthy blood donors were analyzed. The identification of variants was made by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test and multivariate analysis. Individuals carrying the G/A and A/A genotypes for the rs187116 polymorphism showed an increased risk for colorectal cancer (OR = 3.11, 95% CI: 1.87-5.16, P = 0.001 and OR = 3.59, 95% CI: 2.06-6.25, P = 0.001, respectively). After adjusting for age and gender, these same genotypes and the G/G genotype of the rs7116432 polymorphism were associated with TNM stage and tumor location in the colon. Moreover, the A-G (rs187116 and rs7116432) haplotype was associated with increased risk; while, the haplotype G-A (rs187116 and rs7116432) was related with decreased risk. In conclusion, our results suggest that the here analyzed CD44 variants are involved with risk, TNM stage and tumor location in colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of death worldwide. The named "destruction complex" has a critical function in the Wnt/β-catenin pathway regulating the level of β-catenin in the cytoplasm and nucleus. Alterations in this complex lead to the cellular accumulation of β-catenin, which participates in the development and progression of CRC. This study aims to determine the contribution of polymorphisms in the genes of the β-catenin destruction complex to develop CRC, specifically adenomatous polyposis coli (APC) (rs11954856 G>T and rs459552 A>T), axis inhibition protein 1 (AXIN1) (rs9921222 C>T and rs1805105 C>T), AXIN2 (rs7224837 A>G), and dishevelled 2 (DVL2) (2074222 G>A and rs222836 C>T). Genomic DNA from 180 sporadic colorectal cancer patients and 150 healthy blood donors were analyzed. The identification of polymorphisms was made by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test. Increased susceptibility to CRC was associated with the polymorphic variants rs11954856 (APC), rs222836 (DVL2), and rs9921222 (AXIN1). Decreased susceptibility was associated with the polymorphisms rs459552 (APC) and 2074222 (DVL2). Association was also observed with advanced Tumor-Node-Metastasis (TNM) stages and tumor location. The haplotypes G-T in APC (rs11954856-rs459552) and A-C in DVL2 (rs2074222-rs222836) were associated with decreased risk of CRC, while the G-T haplotype in the DVL2 gene was associated with increased CRC risk. In conclusion, our results suggest that variants in the destruction complex genes may be involved in the promotion or prevention of colorectal cancer.

The rs712 polymorphism in a let-7 microRNA-binding KRAS gene has been associated with different types of cancer, however these associations have been inconsistent. The purpose of this study was to determine the association between rs712 polymorphism in a let-7 microRNA-binding KRAS gene comparing breast cancer (BC) patients with healthy subjects from Mexican population.The genotyping of the rs712 polymorphism was performed by polymerase chain reaction (PCR) in 437 BC patients and 414 healthy women.The observed frequencies of the rs712 polymorphism indicated an associated protective factor for BC in the dominant GT+TT model [odds ratio (OR) 0.70, 95% confidence interval (CI) 0.51-0.97, p=0.040). An association between genotype and BC patients was evident in chemotherapy response (allele GT, OR 0.032, 95% CI 0.002-0.505, p=0.014), partial chemotherapy response (genotype GT, OR 0.023, 95% CI 0.001-0.419, p=0.011), and gastric and hematological toxicity (genotype GT, OR 0.115, 95% CI 0.028-0.473, p=0.003), Luminal A BC patients with gastric and hematological toxicity (genotype TT, OR 0.236, 95% CI 0.069-0.805, p=0.021) and tobacco consumption (genotype TT, OR 0.283, 95% CI 0.001-0.802, p=0.037) and Luminal B with metastatic lymph node (genotype GT, OR 0.241, 95% CI 0.093-0.626, p=0.003).Polymorphism rs712 in KRAS gene was protective factor associated with susceptibility for BC in this sample from Mexican population.

Colorectal cancer is the third cause of cancer and the second leading cause of death worldwide. The CD44 gene plays a key role in malignant processes, including growth, survival, epithelial to mesenchymal transition and metastasis. It is also known that some variants as rs187116 (c.67+4883GA) and rs7116432 (c.2024+779AG) can modulate the function of the CD44 gene and malignant transformation in several neoplasms. This study aims to explore, for the first time, the association of the CD44 rs187116 and rs7116432 variants in patients with colorectal cancer. Genomic DNA from 250 patients and 250 healthy blood donors were analyzed. The identification of variants was made by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test and multivariate analysis. Individuals carrying the G/A and A/A genotypes for the rs187116 polymorphism showed an increased risk for colorectal cancer (OR = 3.11, 95% CI: 1.87-5.16, P = 0.001 and OR = 3.59, 95% CI: 2.06-6.25, P = 0.001, respectively). After adjusting for age and gender, these same genotypes and the G/G genotype of the rs7116432 polymorphism were associated with TNM stage and tumor location in the colon. Moreover, the A-G (rs187116 and rs7116432) haplotype was associated with increased risk; while, the haplotype G-A (rs187116 and rs7116432) was related with decreased risk. In conclusion, our results suggest that the here analyzed CD44 variants are involved with risk, TNM stage and tumor location in colorectal cancer.

Resumen: La mayor parte de los seres vivos son capaces de realizar acciones que pueden ser consideradas inteligentes o al menos el resultado de un proceso de reacción adecuado ante las circunstancias cambiantes de su medio ambiente. Sin embargo, la inteligencia o los procesos intelectuales que desarrollan los seres humanos son enormemente superiores a los que logran los organismos de cualquier otra especie. El cerebro humano adulto es un órgano sumamente complejo: pesa aproximadamente 1.500 g, lo que representa solo el 2% del peso corporal pero consume igual cantidad de energía que todo el músculo esquelético en reposo. Aunque el cerebro humano presenta una estructura típicamente primate, revela algunas características que lo distinguen y lo individualizan plenamente.El proceso de evolución y humanización del cerebro del Homo sapiens (H. sapiens) lo convirtió en un órgano único y diferente, alcanzando el mayor tamaño relativo entre todas las especies, pero además le permitió una reorganización estructural de tejidos y circuitos en segmentos y regiones específicas. Esto explica las notables capacidades cognitivas del hombre moderno, en comparación no solo con otros miembros de su género, sino con otros miembros más antiguos de su propia especie.La evolución del cerebro requirió la coexistencia de 2 mecanismos de adaptación. El primero involucra cambios genéticos que ocurren a nivel de especies y el segundo ocurre a nivel individual e involucra cambios en la organización de la cromatina o cambios epigenéticos. Entre los mecanismos genéticos se encuentran: a) cambios en regiones genéticas codificantes que conducen a cambios en la secuencia y actividad de proteínas existentes; b) los procesos de duplicación y deleción de genes previamente existentes; c) cambios en la expresión génica a través de modificaciones en las secuencias reguladoras de diferentes genes, y d) síntesis de ARNs no codificantes.Finalmente, en esta revisión se describen algunas de las más importantes diferencias cromosómicas reportadas entre humanos y grandes simios, que también han contribuido al proceso de evolución y humanización del cerebro del H. sapiens. Abstract: Most living beings are able to perform actions that can be considered intelligent or, at the very least, the result of an appropriate reaction to changing circumstances in their environment. However, the intelligence or intellectual processes of humans are vastly superior to those achieved by all other species. The adult human brain is a highly complex organ weighing approximately 1500 g, which accounts for only 2% of the total body weight but consumes an amount of energy equal to that required by all skeletal muscle at rest. Although the human brain displays a typical primate structure, it can be identified by its specific distinguishing features.The process of evolution and humanisation of the Homo sapiens brain resulted in a unique and distinct organ with the largest relative volume of any animal species. It also permitted structural reorganization of tissues and circuits in specific segments and regions. These steps explain the remarkable cognitive abilities of modern humans compared not only with other species in our genus, but also with older members of our own species.Brain evolution required the coexistence of two adaptation mechanisms. The first involves genetic changes that occur at the species level, and the second occurs at the individual level and involves changes in chromatin organisation or epigenetic changes. The genetic mechanisms include: a) genetic changes in coding regions that lead to changes in the sequence and activity of existing proteins; b) duplication and deletion of previously existing genes; c) changes in gene expression through changes in the regulatory sequences of different genes; and d) synthesis of non-coding RNAs.Lastly, this review describes some of the main documented chromosomal differences between humans and great apes. These differences have also contributed to the evolution and humanisation process of the H. sapiens brain. Palabras clave: Cerebro humano, Genómica del cerebro, Evolución del cerebro, Keywords: Human brain, Brain genomics, Brain evolution

Most living beings are able to perform actions that can be considered intelligent or, at the very least, the result of an appropriate reaction to changing circumstances in their environment. However, the intelligence or intellectual processes of humans are vastly superior to those achieved by all other species. The adult human brain is a highly complex organ weighing approximately 1500 g, which accounts for only 2% of the total body weight but consumes an amount of energy equal to that required by all skeletal muscle at rest. Although the human brain displays a typical primate structure, it can be identified by its specific distinguishing features.The process of evolution and humanisation of the Homo sapiens brain resulted in a unique and distinct organ with the largest relative volume of any animal species. It also permitted structural reorganisation of tissues and circuits in specific segments and regions. These steps explain the remarkable cognitive abilities of modern humans compared not only with other species in our genus, but also with older members of our own species.Brain evolution required the coexistence of two adaptation mechanisms. The first involves genetic changes that occur at the species level, and the second occurs at the individual level and involves changes in chromatin organisation or epigenetic changes. The genetic mechanisms include: (a) genetic changes in coding regions that lead to changes in the sequence and activity of existing proteins; (b) duplication and deletion of previously existing genes; (c) changes in gene expression through changes in the regulatory sequences of different genes; and (d) synthesis of non-coding RNAs.Lastly, this review describes some of the main documented chromosomal differences between humans and great apes. These differences have also contributed to the evolution and humanisation process of the H. sapiens brain. Resumen: La mayor parte de los seres vivos son capaces de realizar acciones que pueden ser consideradas inteligentes o al menos el resultado de un proceso de reacción adecuado ante las circunstancias cambiantes de su medio ambiente. Sin embargo, la inteligencia o los procesos intelectuales que desarrollan los seres humanos son enormemente superiores a los que logran los organismos de cualquier otra especie. El cerebro humano adulto es un órgano sumamente complejo: pesa aproximadamente 1.500 g, lo que representa solo el 2% del peso corporal pero consume igual cantidad de energía que todo el músculo esquelético en reposo. Aunque el cerebro humano presenta una estructura típicamente primate, revela algunas características que lo distinguen y lo individualizan plenamente.El proceso de evolución y humanización del cerebro del Homo sapiens (H. sapiens) lo convirtió en un órgano único y diferente, alcanzando el mayor tamaño relativo entre todas las especies, pero además le permitió una reorganización estructural de tejidos y circuitos en segmentos y regiones específicas. Esto explica las notables capacidades cognitivas del hombre moderno, en comparación no solo con otros miembros de su género, sino con otros miembros más antiguos de su propia especie.La evolución del cerebro requirió la coexistencia de 2 mecanismos de adaptación. El primero involucra cambios genéticos que ocurren a nivel de especies y el segundo ocurre a nivel individual e involucra cambios en la organización de la cromatina o cambios epigenéticos. Entre los mecanismos genéticos se encuentran: a) cambios en regiones genéticas codificantes que conducen a cambios en la secuencia y actividad de proteínas existentes; b) los procesos de duplicación y deleción de genes previamente existentes; c) cambios en la expresión génica a través de modificaciones en las secuencias reguladoras de diferentes genes, y d) síntesis de ARNs no codificantes.Finalmente, en esta revisión se describen algunas de las más importantes diferencias cromosómicas reportadas entre humanos y grandes simios, que también han contribuido al proceso de evolución y humanización del cerebro del H. sapiens. Keywords: Human brain, Brain genomics, Brain evolution, Palabras clave: Cerebro humano, Genómica del cerebro, Evolución del cerebro

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of death worldwide. The named "destruction complex" has a critical function in the Wnt/β-catenin pathway regulating the level of β-catenin in the cytoplasm and nucleus. Alterations in this complex lead to the cellular accumulation of β-catenin, which participates in the development and progression of CRC. This study aims to determine the contribution of polymorphisms in the genes of the β-catenin destruction complex to develop CRC, specifically adenomatous polyposis coli (APC) (rs11954856 GT and rs459552 AT), axis inhibition protein 1 (AXIN1) (rs9921222 CT and rs1805105 CT), AXIN2 (rs7224837 AG), and dishevelled 2 (DVL2) (2074222 GA and rs222836 CT). Genomic DNA from 180 sporadic colorectal cancer patients and 150 healthy blood donors were analyzed. The identification of polymorphisms was made by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test. Increased susceptibility to CRC was associated with the polymorphic variants rs11954856 (APC), rs222836 (DVL2), and rs9921222 (AXIN1). Decreased susceptibility was associated with the polymorphisms rs459552 (APC) and 2074222 (DVL2). Association was also observed with advanced Tumor-Node-Metastasis (TNM) stages and tumor location. The haplotypes G-T in APC (rs11954856-rs459552) and A-C in DVL2 (rs2074222-rs222836) were associated with decreased risk of CRC, while the G-T haplotype in the DVL2 gene was associated with increased CRC risk. In conclusion, our results suggest that variants in the destruction complex genes may be involved in the promotion or prevention of colorectal cancer.

Introduction: Today, scientists accept that the central nervous system of an adult possesses considerable morphological and functional flexibility, allowing it to perform structural remodelling processes even after the individual is fully developed and mature. In addition to the vast number of genes participating in the development of memory, different known epigenetic mechanisms are involved in normal and pathological modifications to neurons and therefore also affect the mechanisms of memory development. Development: This study entailed a systematic review of biomedical article databases in search of genetic and epigenetic factors that participate in synaptic function and memory. Conclusions: The activation of gene expression in response to external stimuli also occurs in differentiated nerve cells. Neural activity induces specific forms of synaptic plasticity that permit the creation and storage of long-term memory. Epigenetic mechanisms play a key role in synaptic modification processes and in the creation and development of memory. Changes in these mechanisms result in the cognitive and memory impairment seen in neurodegenerative diseases (Alzheimer disease, Huntington disease) and in neurodevelopmental disorders (Rett syndrome, fragile X, and schizophrenia). Nevertheless, results obtained from different models are promising and point to potential treatments for some of these diseases. Resumen: Introducción: Hoy en día se acepta que el sistema nervioso central adulto posee una enorme flexibilidad morfofuncional que le permite realizar procesos de remodelación estructural aún después de haber alcanzado su desarrollo y maduración. Además del enorme número de genes que participan en el desarrollo de la memoria, los diferentes mecanismos epigenéticos conocidos también han sido involucrados en procesos de modificación neuronal normal y patológica y, por ende, en los mecanismos de desarrollo de la memoria. Desarrollo: Este trabajo fue llevado a cabo a través de una sistemática revisión de las bases de datos de publicaciones biomédicas sobre los aspectos genéticos y epigenéticos que participan en la función sináptica y la memoria. Conclusiones: La activación de la expresión génica, en respuesta a estímulos extrínsecos, ocurre también en células nerviosas diferenciadas. La actividad neuronal induce formas específicas de plasticidad sináptica que permiten la formación y almacenamiento de la memoria a largo plazo. Los mecanismos epigenéticos tienen un papel crucial en los procesos de modificación sináptica y en la formación y desarrollo de la memoria. Alteraciones en estos mecanismos producen déficit cognitivo y de memoria en padecimientos neurodegenerativos (enfermedad de Alzheimer y Huntington) así como en trastornos del desarrollo neurológico (síndrome de Rett, X-frágil y esquizofrenia). Los resultados obtenidos en diferentes modelos muestran, sin embargo, un escenario promisorio con tratamientos potenciales para algunos de estos padecimientos. Keywords: Epigenetics, Memory, Neural plasticity, Genes and memory, Memory development, Synaptic modification and memory, Palabras clave: Epigenética, Memoria, Plasticidad neuronal, Genes y memoria, Desarrollo de la memoria, Modificación sináptica y memoria

Mutations and polymorphisms of the GSK3β gene have been associated with several diseases including Alzheimer disease, diabetes and cancer; however, to date, no variants of this gene have been associated with colorectal cancer (CRC). This study aims to explore, for the first time, the association of the GSK3β rs334558 and rs6438552 polymorphisms with CRC.Genomic DNA from 330 CRC patients and healthy blood donors were analyzed. Identification of polymorphisms was made by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test.Patients carrying the C/T genotype for the rs334558 (TC) polymorphism showed an increased risk for CRC (OR = 1.71, 95% CI: 1.05-2.79, P = 0.039); this association was also observed for TNM stage and tumor location. For the rs6438552 (TC) polymorphism, the OR analysis showed that patients carrying C/T and C/C genotypes have a decreased risk for CRC (OR = 0.44, 95% CI: 0.27-0.70, P = 0.001 and OR = 0.24, 95% CI: 0.10-0.64, P = 0.001, respectively); this decreased risk was also evident in the stratified analysis by TNM stage and tumor location. Haplotype analysis of these 2 loci of GSK3β (rs334558 and rs6438552) showed differential distribution. The T-T and C-C haplotype was associated with a decreased risk of CRC, while the T-C haplotype was associated with an increased risk of CRC.Our results denote that GSK3β gene polymorphisms play a significant role in promoting or preventing CRC. Additionally, variations in this gene are associated with the tumor site and the tumor-node-metastasis (TNM) stage in these patients.

PPARD encodes for peroxisome proliferator-activated receptor delta, which plays a significant role in controlling lipid metabolism, atherosclerosis, inflammation, cancer growth, progression, and apoptosis. Accumulated evidence suggests that the polymorphism rs2016520 in PPARD is associated with lipid metabolism, obesity, metabolic syndrome, and type 2 diabetes mellitus. The aim of this study was to determine whether the single nucleotide polymorphism +294T/C (rs2016520) in PPARD is associated with colorectal cancer (CRC) in the Mexican population. Genomic DNA from 178 CRC patients and 97 healthy blood donors was analyzed. The polymorphism was identified by the polymerase chain reaction-restriction fragment length polymorphism method. Results demonstrated that patients with the T/C genotype for the +294T/C (rs2016520) polymorphism present a protective role against CRC [odds ratio (OR) = 0.39; 95% confidence interval (CI) = 0.22-0.69; P = 0.0008]. This association was also evident for the T/C genotype in the stratified analysis by tumor-node-metastasis stages I+II (OR = 0.26, P = 0.0332) and III+IV (OR = 0.44, P = 0.0067). However, in the stratified analysis by tumor location, we observed an increased risk of rectal cancer (OR = 7.57, P = 0.0403) vs colon cancer (OR = 4.87, P = 0.234) in patients carrying the C/C genotype and under the dominant and recessive models of inheritance. In conclusion, for the first time, the association between the +294T/C (rs2016520) polymorphism and colorectal cancer has been studied in Mexican patients. Our results reveal that variations in PPARD may play a significant role in genetic susceptibility to colorectal cancer.

The aim of this review is to present a general overview about the importance of micro RNAs (miRNAs) in colorectal carcinoma. First, we focused on the mechanisms whereby the miRNAs regulate the expression of target genes, and how an altered regulation of them is associated with several types of cancer, including colorectal carcinoma. Later, examples of some miRNAs that have been associated with cancer development and how the expression patterns of specific miRNAs can be used as potential biomarkers for prognosis, diagnosis and therapeutic outcome in colorectal carcinoma are addressed. Finally, several polymorphisms presents in the miRNAs that have been associated to risk and prognosis in colorectal carcinoma are described.

The aim of this study was to investigate the association of the rs2240308 and rs1133683 polymorphisms in the AXIN2 gene with colorectal cancer (CRC) in Mexican patients.Genomic DNAs from 201 CRC patients and 100 healthy blood donors were analyzed for AXIN2 gene polymorphisms by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Statistical associations were calculated using the odds ratio (OR) test.The genotype distribution of the rs1133683 polymorphism C T showed a statistical difference between the two study groups (p = 0.0019). Moreover, OR analyses demonstrated that individuals with either the C/T or T/T genotype have a decreased risk for CRC compared with individuals with the C/C genotype (OR = 0.47, 95% confidence interval [CI] = 0.25-0.86, p = 0.0134 and OR = 0.24, 95% CI = 0.10-0.57, p = 0.005, respectively). This association was also evident in a stratified analysis based on tumor-node-metastasis (TNM) stage. For the rs2240308 polymorphism C T, the OR analysis showed a significantly increased risk for carriers of the T/T genotype (OR = 2.64, 95% CI = 1.12-6.24, p = 0.0236) and this association was also evident in the stratified analysis by TNM stage.Our results indicate the possibility that variations in the AXIN2 gene may play a significant role in promoting or preventing CRC development.