Cáncer colorrectal. Variantes génicas en la vía de señalización BMP y ancestría en población mexicana / Colorectal cancer. Genetic variants in BMP signaling pathway and ancestry in the Mexican population

Resumen Introducción: Variantes génicas relacionadas con la vía de señalización de las proteínas morfogenéticas óseas (BMP2, BMP4, GREM1, SMAD7) se han asociado a cáncer colorrectal, principalmente en poblaciones caucásicas. Objetivo: Describir la asociación de variantes en miembros de la vía BMP en población mexicana, caracterizada por su ancestría indoamericana y caucásica. Métodos: Se realizó el genotipado de 1000 casos de cáncer colorrectal y 1043 individuos de control reclutados en la Ciudad de México, Monterrey y Torreón mediante la plataforma Sequenom. Con análisis univariados y multivariados se estudiaron las asociaciones entre cáncer colorrectal y variantes. Resultados: Las variantes rs4444235, rs12953717 y rs4939827 replicaron la asociación con la neoplasia (p ≤ 0.05). La ascendencia caucásica mostró asociación con el tumor. Conclusiones: El estudio mostró las asociaciones entre cáncer colorrectal y las variantes SMAD7 y BMP4, así como con el componente caucásico de la mezcla étnica.

Abstract Introduction: Genetic variants related to bone morphogenetic proteins (BMP2, BMP4, GREM1, SMAD7) signaling pathway have been associated with colorectal cancer, mainly in Caucasian populations. Objective: To describe the association of variants in members of the BMP signaling pathway in a Mexican population, characterized by its indigenous American and Caucasian ancestry. Methods: Genotyping of 1,000 colorectal cancer cases and 1,043 control individuals recruited in Mexico City, Monterrey, and Torreón was carried out using the Sequenom platform. Associations between colorectal cancer and variants were studied with univariate and multivariate analyses. Results: Variants rs4444235, rs12953717 and rs4939827 replicated the association with the neoplasm (p ≤ 0.05). Caucasian ancestry showed association with the tumor. Conclusions: The study replicated the associations between colorectal cancer and SMAD7 and BMP4 variants, with an association being observed with the Caucasian component of the ethnic mix.

Colorectal cancer. Genetic variants in BMP signaling pathway and ancestry in the Mexican population.

INTRODUCTION: Genetic variants related to bone morphogenetic proteins (BMP2, BMP4, GREM1, SMAD7) signaling pathway have been associated with colorectal cancer, mainly in Caucasian populations. OBJECTIVE: To describe the association of variants in members of the BMP signaling pathway in a Mexican population, characterized by its indigenous American and Caucasian ancestry. METHODS: Genotyping of 1,000 colorectal cancer cases and 1,043 control individuals recruited in Mexico City, Monterrey, and Torreón was carried out using the Sequenom platform. Associations between colorectal cancer and variants were studied with univariate and multivariate analyses. RESULTS: Variants rs4444235, rs12953717 and rs4939827 replicated the association with the neoplasm (p ≤ 0.05). Caucasian ancestry showed association with the tumor. CONCLUSIONS: The study replicated the associations between colorectal cancer and SMAD7 and BMP4 variants, with an association being observed with the Caucasian component of the ethnic mix.

INTRODUCCIÓN: Variantes génicas relacionadas con la vía de señalización de las proteínas morfogenéticas óseas (BMP2, BMP4, GREM1, SMAD7) se han asociado a cáncer colorrectal, principalmente en poblaciones caucásicas. OBJETIVO: Describir la asociación de variantes en miembros de la vía BMP en población mexicana, caracterizada por su ancestría indoamericana y caucásica. MÉTODOS: Se realizó el genotipado de 1000 casos de cáncer colorrectal y 1043 individuos de control reclutados en la Ciudad de México, Monterrey y Torreón mediante la plataforma Sequenom. Con análisis univariados y multivariados se estudiaron las asociaciones entre cáncer colorrectal y variantes. RESULTADOS: Las variantes rs4444235, rs12953717 y rs4939827 replicaron la asociación con la neoplasia (p ≤ 0.05). La ascendencia caucásica mostró asociación con el tumor. CONCLUSIONES: El estudio mostró las asociaciones entre cáncer colorrectal y las variantes SMAD7 y BMP4, así como con el componente caucásico de la mezcla étnica.

Increased Urinary Concentration of C-Terminal Telopeptide of Type II Collagen and Pain by Radiographic Grade in Women with Knee Osteoarthritis in Northeastern Mexico: A Cross-Sectional Study.

Osteoarthritis (OA) of the knee causes disability, pain, and progressive destruction of cartilage in adult women. The objective of the study was to evaluate the concentrations of the urinary biomarker C-terminal telopeptide of type II collagen (CTX-II) and pain by radiographic grade in women with knee OA in northeastern Mexico: Cross-sectional study of 155 women with knee OA. Concentrations of biochemical parameters were evaluated and urine samples were collected to measure biomarker levels (uCTX-II) ng/mmol by competitive enzyme-linked immunoabsorbent assay (ELISA) technique and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale was used for pain classification; median age of 49 years and 29.1 kg/m2 of body mass index (BMI). uCTX-II biomarker levels were grade 2 (210.7 ng/mmol), grade 3 (314.8 ng/mmol), and grade 4 (478.8 ng/mmol) relative to Kellgren and Lawrence, uCTX-II levels were compared with WOMAC scale and presented significant statistical difference (p = 0.0001). An association of the biomarker CTX-II and an increase in BMI was found in female patients with knee OA (odds ratio = 1.01; 95% confidence interval 1.001-1.005; p = 0.047).This study demonstrates an increase in the levels of the biomarker uCTX-II, the degree of pain, and radiographic grade in women with knee OA in northeastern Mexico.

Genetic diversity of HLA system in two populations from Nuevo León, Mexico: Monterrey and rural Nuevo León.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 665 Mexicans from the state of Nuevo León living in the city of Monterrey (N = 226) and rural communities (N = 439), to obtain information regarding allelic and haplotypic frequencies. We find that the most frequent haplotypes in the state of Nuevo León include 12 Native American and three European haplotypes. Admixture estimates revealed that the main genetic components in the state of Nuevo León are Native American (54.53 ±â€¯0.87% by ML; 48.88% of Native American haplotypes) and European (38.67 ±â€¯4.06% by ML; 32.59% of European haplotypes), and a less prominent African genetic component (6.80 ±â€¯4.30% by ML; 8.26% of African haplotypes).

Genetic diversity of HLA system in two populations from Durango, Mexico: Durango city and rural Durango.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 479 Mexicans from the state of Durango living in Durango city (N = 153) and rural communities (N = 326), to obtain information regarding allelic and haplotypic frequencies. We find that the ten most frequent haplotypes found in the state of Durango include eight Native American and two European haplotypes. Admixture estimates revealed that the main genetic components in Durango are European (54.34 ±â€¯1.68%) and Native American (45.66 ±â€¯2.24%), while African genetic component was virtually absent (0.00 ±â€¯2.03%). However, African haplotypes could be estimated at a proportion of 9.13%.

Genetic diversity of HLA system in three populations from Chihuahua, Mexico: Chihuahua City, Ciudad Juárez and rural Chihuahua.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 461 Mexicans from the state of Chihuahua living in Chihuahua city (N = 119), Ciudad Juárez (N = 106) and rural communities (N = 236), to obtain information regarding allelic and haplotypic frequencies and their linkage disequilibrium. We find that the most frequent haplotypes found in the state of Chihuahua include seven Native American and three European haplotypes. Admixture estimates revealed that the main genetic components in Chihuahua are European (52.12 ±â€¯0.88% by ML; 41.53% of European haplotypes) and Native American (39.51 ±â€¯2.17% by ML; 37.45% of Native American haplotypes), while African genetic component was less apparent (8.36 ±â€¯1.47% by ML; 11.70% of African haplotypes).

Genetic diversity of HLA system in a population sample from Aguascalientes, Mexico.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 95 Mexicans from the state of Aguascalientes to obtain information regarding allelic and haplotypic frequencies and their linkage disequilibrium. We find that the most frequent haplotypes in the state of Aguascalientes include four Native American, three European and one Asian haplotypes. Admixture estimates revealed that the main genetic components in the state of Aguascalientes are Native American (54.53 ±â€¯3.22% by ML; 44.21% of Native American haplotypes) and European (44.34 ±â€¯0.45% by ML; 40.53% of European haplotypes), and a relatively low African genetic component (1.13 ±â€¯2.33% by ML; 5.26% of African haplotypes).

Genetic diversity of HLA system in two populations from Tamaulipas, Mexico: Ciudad Victoria and rural Tamaulipas.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 148 Mexicans from the state of Tamaulipas living in Ciudad Victoria (N = 23) and rural communities (N = 125), to obtain information regarding allelic and haplotypic frequencies. We found that the most frequent haplotypes in the state of Tamaulipas include ten Native American, three European and one African haplotypes. Admixture estimates revealed that the main genetic components in the state of Tamaulipas are Native American (54.69 ±â€¯0.93% by ML; 47.65% of Native American haplotypes) and European (34.66 ±â€¯5.62% by ML; 33.56% of European haplotypes), and a relatively high African genetic component (10.65 ±â€¯5.05% by ML; 12.42% of African haplotypes).

Genetic diversity of HLA system in two populations from San Luis Potosí, Mexico: San Luis Potosí City and rural San Luis Potosí.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 117 Mexicans from the state of San Luis Potosí living in the city of San Luis Potosí (N = 30) and rural communities (N = 87), to obtain information regarding allelic and haplotypic frequencies. We find that the most frequent haplotypes in the state include 13 Native American, six European, two African and two Asian haplotypes. Admixture estimates revealed that the main genetic components are Native American (52.72 ±â€¯0.66% by ML; 48.29% of Native American haplotypes) and European (34.62 ±â€¯4.28% by ML; 32.48% of European haplotypes), and a relatively high African genetic component (12.66 ±â€¯4.61% by ML; 10.26% of African haplotypes).

Genetic diversity of HLA system in three populations from Coahuila, Mexico: Torreón, Saltillo and rural Coahuila.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 684 Mexicans from the state of Coahuila living in Saltillo (N = 72), Torreón (N = 396) and rural communities (N = 216), to obtain information regarding allelic and haplotypic frequencies. We find that the ten most frequent haplotypes found in the state of Coahuila include eight Native American and two European haplotypes. Admixture estimates revealed that the main genetic components in the state of Coahuila are European (49.72 ±â€¯4.18% by ML; 37.49% of European haplotypes) and Native American (45.01 ±â€¯2.69% by ML; 42.98% of Native American haplotypes), while African genetic component is less apparent (5.27 ±â€¯1.88% by ML; 9.92% of African haplotypes).

Genetic diversity of HLA system in three populations from Zacatecas, Mexico: Zacatecas city, Fresnillo and rural Zacatecas.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 453 Mexicans from the state of Zacatecas living in Zacatecas city (N = 84), Fresnillo (N = 103) and rural communities (N = 266) to obtain information regarding allelic and haplotypic frequencies and their linkage disequilibrium. We find that the most frequent haplotypes for the state of Zacatecas include seven Native American most probable ancestry (A*02 ∼ B*39 ∼ DRB1*04 ∼ DQB1*03:02; A*02 ∼ B*35 ∼ DRB1*08 ∼ DQB1*04; A*24 ∼ B*39 ∼ DRB1*14 ∼ DQB1*03:01; A*02 ∼ B*35 ∼ DRB1*04 ∼ DQB1*03:02; A*24 ∼ B*35 ∼ DRB1*04 ∼ DQB1*03:02; A*68 ∼ B*35 ∼ DRB1*04 ∼ DQB1*03:02 and A*24 ∼ B*35 ∼ DRB1*08 ∼ DQB1*04) and two European MPA haplotypes (HLA ∼ A*01 ∼ B*08 ∼ DRB1*03:01 ∼ DQB1*02 and A*29 ∼ B*44 ∼ DRB1*07 ∼ DQB1*02). Admixture estimates revealed that the main genetic components in the state of Zacatecas are European (47.61 ±â€¯1.85%) and Native American (44.74 ±â€¯1.12%), while the African genetic component was less apparent (7.65 ±â€¯1.12%). Our findings provide a starting point for the study of population immunogenetics of urban and rural populations from the state of Zacatecas and add to the growing knowledge on the population genetics of Northern Mexico.

Study of polymorphisms in the TP53 and RB1 genes in children with retinoblastoma in northern Mexico.

PURPOSE: To determine the frequency and association of polymorphisms in the TP53 and RB1 genes with clinical characteristics in a group of children with retinoblastoma (RB) in northern Mexico. METHODS: A prospective, longitudinal, and analytical study of 11 patients diagnosed with RB was conducted. Endpoint PCR and high-resolution real-time PCR were performed. Chi-square and Student t tests were used to evaluate associations between variables. Allelic frequencies, as well as genotypic and Hardy-Weinberg equilibriums, were evaluated using Guo and Thompson's method. RESULTS: We found a statistically significant difference between the polymorphism RB1-GG/rs9568036 and tumor chemoresistance (p<0.05). The allelic variants RB1-AA and AG/rs9568036 were determined to be associated with tumor chemosensitivity (p<0.05). A statistically significant relation between the polymorphism RB1-GG/rs9568036 and males (p = 0.0386), rate ratio (RR) = 2.0 (95% confidence interval [CI] = 0.76-5.32), as well as between the allelic variants RB1-AA and AG/rs9568036 and females (p = 0.0027), RR = 8.0 (95% CI = 1.28-50.04), was observed. We also observed a statistically significant association between the rs1042522 polymorphism in the TP53 gene and unilateral presentation of the disease. CONCLUSIONS: The rs9568036 polymorphism in the RB1 gene and the allelic variants can be associated with type of response to medical therapy and associated with male sex, while the allelic variant rs1042522 polymorphism in the TP53 gene is associated with the unilateral presentation of the disease in a group of Mexican children with RB.

Duplicación del tubo digestivo manifestada como quiste lingual: Caso clínico y revisión de la literatura / Enteric duplication presented as lingual cyst: Case report and literature review

Introducción: Los quistes de duplicación intestinal son anormalidades poco frecuentes que se presentan principalmente en el período perinatal, y pueden causar problemas respiratorios y para la alimentación. Los quistes sublinguales de duplicación intestinal pueden presentar solo epitelio del aparato digestivo, del respiratorio o de ambos. En los dos últimos casos se denominan coristomas. Caso clínico: Se describe un caso de un paciente de 10 meses de edad que presentó una masa quística sublingual desde el nacimiento. Se realizó la resección total con abordaje transoral y la reconstrucción de la lengua en planos. La pieza quirúrgica resultó una estructura quística de contenido mucoide, de 23 × 17 × 11 mm y color marrón. El revestimiento del quiste estaba formado por mucosa gástrica, con epitelio foveolar y glándulas formadas por células parietales y principales. Conclusiones: El quiste de duplicación intestinal es una entidad extremadamente rara. El abordaje quirúrgico es eficaz y curativo con mínima morbilidad y mortalidad, sin recurrencia en su seguimiento.

Background: Intestinal duplication cysts are rare abnormalities that occur primarily during the perinatal period and may cause problems for feeding and/or breathing. Sublingual intestinal duplication cysts can present either gastrointestinal epithelium or respiratory or both; the latter two cases are called choristomas. Case report: We describe a 10-month-old infant who presented a sublingual cystic mass at birth. Total successful transoral resection and reconstruction of the tongue was performed in planes. The surgical specimen was a brown cystic structure of mucoid content with dimensions of 23 × 17 × 11 mm. The cyst lining consists of gastric mucosa with foveolar epithelium and glands composed of parietal and chief cells. Conclusions: The intestinal duplication cyst is an extremely rare entity. The surgical approach is effective and curative with minimal morbidity and mortality and without recurrence in follow-up.

YAP expression in normal and neoplastic breast tissue: an immunohistochemical study.

BACKGROUND AND AIMS: Yes-associated protein (YAP) is a transcriptional factor involved in normal cell proliferation, apoptosis and carcinogenesis; however, its contribution to breast cancer (BC) is still controversial. We undertook this study to compare the expression of YAP by immunohistochemistry (IHC) in normal breast tissue of women without breast cancer (BC) (controls), non-neoplastic breast tissue in women with cancer (internal controls) and in four different subtypes of invasive ductal carcinoma. METHODS: There were 17 controls and 105 tumor cases (53 luminal A, 15 luminal B, 20 overexpression of HER2 and 17 triple negative cases) studied by IHC. Statistical analysis included χ(2) for linear trend (Extended Mantel-Haenszel). RESULTS: There were 40% of internal controls that showed expression of YAP in myoepithelial cells, whereas in controls expression was 100%. In controls, 3/17 (17.6%) showed cytoplasmic staining in luminal cells. There was a significant difference in nuclear expression between the ductal BC subtypes. Luminal A had 4% of positive cases with <10% of cells affected in each case; in contrast, there were 17-20% of positive cases in the other groups with 50% or more of stained cells. YAP expression in stromal cells was not observed in controls or in triple-negative cases, and luminal B pattern had the highest YAP nuclear expression (20%). CONCLUSIONS: YAP showed decreased expression in tumor cells compared with normal breast tissue. These findings are consistent with a role of YAP as a suppressor gene in BC and show differences in YAP expression in different patterns of ductal BC.

Chronic gastritis associated with Helicobacter pylori in Mexican children: histopathological patterns.

The objective of this study was to analyze the histopathological patterns of inflammation, distribution, severity, and degree of gastric mucosa of Helicobacter pylori (Hp)-infected children in Northern Mexico, as well as the correlation between colonization density and inflammation intensity. We carried out a cross-sectional study of gastric biopsies performed on children ranging from 2 to 17 years of age who underwent upper gastrointestinal endoscopy for diverse gastroduodenal disorders. This study includes only children who were found to be Hp carriers, with positive results for tests of Hp antigens in feces and in gastric biopsy studies. We studied 107 patients (age 8.2 ± 3.7 years). In 47.7% of patients, the density of Hp colonization was low; only 21.5% had a marked density. Mononuclear leukocyte infiltration showed a similar distribution. Thirty-seven percent of patients had follicular gastritis. An acute inflammatory response was absent in 65% and mild in 20.6% of patients. When inflammation was present, it was primarily located in the antrum (79%). There were no cases of intestinal metaplasia or atrophy. A link was found between Hp density and age, infiltration by mononuclear cells, the presence of follicular gastritis, and the level of neutrophil infiltration (P  =  0.001). Despite the high rates of Hp infection in the region, the histopathological findings in these children were mild and were limited primarily to the antral mucosa. These data indicate the need to study the behavior of this disease in children in diverse study populations to provide localized prevention and treatment strategies.

Immunochromatographic monoclonal test for detection of Helicobacter pylori antigen in stool is useful in children from high-prevalence developing country.

BACKGROUND: Tests to detect Helicobacter pylori antigens in feces for diagnosis of infection in children demonstrate controversial results. One novel and fast monoclonal test improves diagnostic accuracy in adults, but clinical evidence of its usefulness at pediatric age is insufficient to date. The objective of this work was to evaluate the diagnostic accuracy of this test in a sample of Mexican children. METHODS: We conducted a transversal study in 150 selected children with digestive symptoms suggestive of organic disease in whom a clinical history was conducted in addition to a fast monoclonal test (ImmunoCardSTAT HpSA, Meridian Diagnostics) performed by immunochromatography. Patients were submitted to endoscopy and histopathologic study. RESULTS: Of the 150 children (mean age 7.8 +/- 4.7 years), 107 (71.3%) were positive for the test, and presence of H. pylori was confirmed histologically in 109 (72.7%) children, with sensitivity of 96.3% (95% CI = 95.8-96.8), specificity of 95.1% (95% CI = 93.9-96.4), and accuracy of 96.0% (95% CI, -95.6 to -96.3); pretest probability was 0.73, while post-test probability was 0.98. Infection rate and test accuracy increased with age. CONCLUSIONS: This test is useful for detecting H. pylori infection in children of all ages, and is a good alternative for screening studies in developing countries with elevated prevalence, due to its being fast, noninvasive, inexpensive, and easy to carry out.

Coccidioidomicosis pulmonar y pleural de difícil diagnóstico. Informe de tres casos / Coccidioidal pneumoniae and pleural coccidioidomycosis, a difficult diagnostic. Three cases report

Se estudiaron tres pacientes con coccidioidomicosis; dos de ellos tuvieron una forma neumónica aguda que resultó ser idéntica clínica y dariológicamente a una neumonía bacteriana, el otro enfermo tuvo una pleuritis crónica granulomatosa muy parcida a la tuberculosa. En todos los pacientes el diagnóstico inicial fue erróneo y sólo pudo establecerse el de coccidioidomicosis cuando se practicaron los estudios necesarios para demostrar el hongo en el lavado broncoalveolar o en la biopsia pleural. Todos los pacientes respondieron favorablemente al tratamiento con anfotericina B, 3 g dosis total, y fluconazol, 400 mg diarios, durante un año

Tercer caso de capilariasis hepática humana en México / Third case of human hepatic capillariasis in Mexico

Se presenta un caso de capilariasis hepática en una mujer de 54 años que estuvo confinada en una institución psiquiátrica. Ingresó al Hospital General de México para recibir cuidados terminales de un cáncer avanzado de mama; murió 12 días después de su ingreso. Clínicamente se detectó hepatomegalia y en la autopsia se encontraron numerosos huevecillos de Capillaria hepática en el hígado. No se observó eosinofilia. Veintiséis casos de capilariasis hepática humana se han registrado en la literatura mundial. Este caso es el tercero que se presenta en la república mexicana, y mientras que los dos primeros ocurrieron en niños éste es el primero en un adulto. Por haber tenido un padecimiento psiquiátrico importante, la paciente pudo haber tenido hábitos alimenticios aberrantes. Por primera vez se describen e ilustran los huevecillos de C. hepática teñidos con metenamina de Jones, lo que permite demostrar una capa multilaminada interna y otra externa dotada de canalículos radiados

Biopsia de próstata por aspiración / Needle-suction prostate biopsy

Se estudiaron 156 pacientes a los cuales se les practicó biopsia de próstata por aspiración según el método de Franzen. Del total de los pacientes, en 110 se emitió el diagnóstico de tejido benigno y en 20 el de malignidad, y se obtuvo confirmación histológica en 75 pacientes operados. Con los resultados obtenidos se demostró que en menos de los autores el método tuvo especificidad de 100 por ciento, sensibilidad de 86.6 por ciento, valor de predicción positivo de 1 y valor de predicción negativo de 0.967, con morbilidad de 1.2 por ciento. Lo anterior confirma que la biopsia de próstata por aspiración es un método útil digno de confianza como instrumento diagnóstico para identificar la presencia de enfermedad prostática, benigna o maligna, con un alto índice de seguridad