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PURPOSE: The relationship between dietary zinc (Zn) intake, metabolic diseases, and telomere length has been little explored in the children population. This observational cross-sectional study assesses the association between obesity (OB), cardiometabolic traits, telomere length, and dietary Zn intake in children with normal weight (NW) and OB from Mexico City. METHODS: Anthropometric data, blood pressure, biochemical measurements, the homeostatic model assessment of insulin resistance (HOMA-IR) and leucocyte telomere length (determined by quantitative-PCR) were analyzed in 171 children with NW and 172 with OB. Furthermore, dietary Zn intake was evaluated in 117 children NW and 120 with OB. RESULTS: Telomere shortening was associated with fasting plasma insulin (FPI) and HOMA-IR in NW (beta coefficient [ß]FPI = -0.022 ± 0.008, p = 0.009; ßHOMA-IR = -0.096 ± 0.040, p = 0.020) and OB (ßFPI = -0.007 ± 0.002, p = 0.003; ßHOMA-IR = -0.034 ± 0.012, p = 0.005) children. Dietary Zn intake resulted negatively associated with FPI (ß = -2.418 ± 0.764, p = 0.002) and HOMA-IR (ß = -0.399 ± 0.014, p = 0.009) in children with OB. Then, in children with OB, the association between FPI, HOMA-IR, and telomere shortening was evaluated separately in groups of low, medium, and high dietary Zn intake (according to tertiles). The association between FPI, HOMA-IR, and telomere shortening was not significant in the high Zn intake group (PFPI = 0.633; PHOMA-IR = 0.567). CONCLUSION: Our results suggest that a high Zn intake may ameliorate the telomere shortening related to high FPI and HOMA-IR.
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Background: Breast cancer shows significant clinical, morphologic, and molecular variation. Telomeres are nucleoprotein complexes composed of hexanucleotide repeat DNA sequence, TTAGGG, and numerous telomere-associated proteins. The maintenance of telomere length is carried out by a ribonucleoprotein called telomerase, which consists of two main components: a catalytic subunit called hTERT (human telomerase reverse transcriptase) and an RNA template called hTR (human telomerase RNA). The importance of evaluating hTERT expression lies in its potential therapeutic application, being an attractive target due to its almost non-existent expression in normal somatic cells. It is also expected that the anti-neoplastic effect would appear earlier in neoplastic cells with shorter telomeres. Additionally, a significant relationship has been observed between Her2-Neu overexpression and Her2-Neu positivity, which could suggest new combined therapies.The aim of this study was to detect the expression of hTERT, estrogen receptor (ER), progesterone receptor (PR), and HER2-Neu in neoplastic breast tissue embedded in paraffin before treatment and to investigate the relationship between them and with baseline and post-treatment telomere length, as well as with various clinicopathological parameters. Materials and methods: A cross-sectional-correlational, 21 women diagnosed with breast cancer at the Oncology Service of the High Specialty Medical Unit No. 1 of Bajio of the Mexican Institute of Social Security. The study complies with the Helsinki Declaration and was approved by the Institutional Ethical Committee of the Mexican Institute of Social Security (R-2019-1001-127). A peripheral blood sample was obtained before oncological treatment and at the end of oncological treatment for the measurement of telomere length by extracting DNA from leukocytes, was performed by the quantitative polymerase chain reaction (PCR) method described by Cawthon. Tumor samples were collected from each patient at the oncology department for immunohistochemical determination of biomarker expression (ER, PR, Her2/neu) and hTERT. Results: Of the 21 cases included in the study, the median age was 57.57 years. Eighteen cases were classified as invasive ductal carcinoma NOS (85.71%), 10 were histologic grade 2 (47.61%), 16 cases were hormone receptor positive (76.19%), 7 were Her2Neu positive (33.33%), and only 2 cases were triple negative (9.52%). Positive hTERT expression was detected in 11 cases (52.38%) and was negative in the remaining cases. A significant association was identified between hTERT-positive cases and Her2-Neu positive cases (p = 0.04). Baseline and post-treatment telomere lengths showed a significant difference using the non-parametric Wilcoxon t-test (p = 0.002). In hTERT-positive cases, there was significant telomere shortening at the end of oncological treatment (6.14 ± 1.54 vs. 4.75 ± 1.96 Kb, p = 0.007). Conclusion: Positive hTERT immunostaining cases were associated with poor prognostic factors, such as Her2-Neu overexpression and post-treatment telomere shortening. In the future, hTERT immunostaining could be used to select patients for therapies with antagonistic effects on hTERT, as well as in the selection of more appropriate chemotherapy regimens for patients who express it.
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BACKGROUND: Fatty acids (FA) likely affect human fertility at multiple levels, as deviations from physiological FA profiles are obesogenic, and FA can modify DNA methylation (DNAm). Yet, the interplay of follicular fluid (FF) and serum FA with BMI and percentage body fat (PBF) in human fertility is not completely understood. Also, associations of DNAm with fertility are largely unexplored. METHODS: Reproductive parameters ranging from retrieved oocyte number to infant birth weight, were recorded in Mexican women undergoing in vitro fertilization (n = 88). Multiple regression analysis sought BMI-adjusted and age-adjusted associations. Receiver operating characteristic analysis tested for discrimination between outcomes. RESULTS: Associations of FF and serum FA were markedly distinct. While various FF FA (C16:1, C18:0, C20:2, C20:3, arachidonic acid) were significantly and inversely associated only with retrieved oocyte number, selected serum FA were associated with a broad range of pre-fertilization and post-fertilization parameters. Associations of BMI and FF FA were complex, as arachidonic acid was inversely associated with both BMI and retrieved oocyte number, while oleic acid (OA) was directly associated with BMI and PBF. Ultrasound-assessed clinical pregnancy outcome (CP) was directly associated with serum OA but inversely with its trans isomer elaidic acid (EA) and with BMI. Compounded BMI, serum EA and OA discriminated CP well (AUC = 0.74). Whole blood DNA methylation was significantly associated with and a moderate predictor (AUC = 0.66) of percent fertilized oocytes. CONCLUSIONS: Overall FF FA pool composition rather than FA identity may impact oocyte production and cellular memory of FF FA is lost as the oocyte exits the follicular environment. The contrasting associations of BMI, FF OA and arachidonic acid suggest that the control of oocyte homeostasis by FF FA is uncoupled from BMI. Further studies are warranted to assess the potential of compounding BMI with serum EA and OA to predict CP.
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Metilación de ADN , Ácidos Grasos , Embarazo , Humanos , Femenino , Fertilización In Vitro , Fertilidad , Ácidos AraquidónicosRESUMEN
BACKGROUND: Some evidence has shown that malignant breast tumours have lower electrical impedance than surrounding normal tissues. Electrical impedance could be used as an indicator for breast cancer detection. The purpose of our study was to analyse the sensitivity and specificity of electrical impedance mammography (EIM) and its implementation for the differential diagnosis of pathological lesions of the breast, either alone or in combination with mammography/ultrasound, in 1200 women between 25 and 70 years old. METHODS: This study is a prospective, cross-sectional epidemiological observational study of serial screening. The women were invited to participate and signed a consent letter. Impedance imaging of the mammary gland was evaluated with the computerized mammography equipment of MEIK electroimpedance v.5.6. (0.5 mA, 50 kHz), developed and manufactured by PKF SIM-Technika®. The successful identification of breast cancer along with the sensitivity, specificity, and positive and negative predictive values of EIM were determined as follows: % sensitivity; % specificity; % positive predictive value (PPV); and % negative predictive value (NPV). RESULTS: EIM had a sensitivity of 85% and a specificity of 96%; the positive predictive value was 12%, and the negative predictive value was 99%. Seven cases were biopsy confirmed cancers. Significant correlations between the electrical conductivity index and body mass index (BMI) (p = 0.04) and patient age were observed (p = 0.01). We also observed that the average conductivity distribution increased according to age group (p = 0.001). We used the chi-squared test to assess the interactions between percent density and BMI (normal < 25 kg/m2 (n = 310), overweight 25-29.9 kg/m2 (n = 418) and obese ≥30 (n = 437)) (p < 0.05). The patients with a diagnosis of mammary carcinoma had a BMI of 35.51 kg/m2. CONCLUSIONS: Our results demonstrate that the use of monofrequency electrical impedance mammography (EIM) in the detection of breast cancer had a sensitivity and specificity of 85 and 96%, respectively. These findings may support future research in the early detection of breast cancer. EIM is a non-radiation method that may also be used as a screening method for young women with dense breasts and a high risk of developing breast cancer.
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Neoplasias de la Mama/diagnóstico , Glándulas Mamarias Humanas/diagnóstico por imagen , Mamografía , Adulto , Anciano , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Estudios Transversales , Detección Precoz del Cáncer , Femenino , Humanos , Masculino , Glándulas Mamarias Humanas/patología , Persona de Mediana EdadRESUMEN
Oocyte maturation defect is a challenging situation in the management of infertility, the etiology may be related to endocrine causes, protocols used in ovarian stimulation, oocyte intrinsic defects or procedures in embryology laboratory. We report three Mexican females in treatment for primary infertility with non-mature oocytes after ovary stimulation and oocyte capture in whom a genetic diagnosis of TUBB8-oocyte maturation defect was revealed by exome sequencing. Two couples achieved pregnancies though oocyte donation after establishing the genetic etiology. Our results expand the role of TUBB8-disorders in patients of non-Asian ethnicity. Oocyte maturation defects of monogenic origin are a growing group of disorders that endocrinologists and reproductive medicine specialists should be aware in order to provide referral to genetics for establish a correct and opportune diagnosis.
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Enfermedades Genéticas Congénitas/terapia , Infertilidad Femenina/diagnóstico , Infertilidad Femenina/terapia , Oogénesis/genética , Tubulina (Proteína)/genética , Adulto , Análisis Mutacional de ADN , Femenino , Enfermedades Genéticas Congénitas/diagnóstico , Enfermedades Genéticas Congénitas/epidemiología , Humanos , Infertilidad Femenina/epidemiología , Infertilidad Femenina/genética , México , Mutación , Linaje , Embarazo , Pronóstico , Técnicas Reproductivas Asistidas/estadística & datos numéricos , Resultado del TratamientoRESUMEN
INTRODUCTION: Malnutrition is common in haemodialysis patients and closely related to morbidity and mortality. We evaluated the effect of twelve weeks of supplementation with resveratrol and curcumin on recovery of bone and muscle mass and protein oxidation, lipid peroxidation on patients with chronic kidney disease and iron overload undergoing hemodialysis, we performed a randomized, double-blind, placebo-controlled trial. METHODS: We included a total of 40 patients, were randomly assigned to two groups, 20 to the group with antioxidant supplementation (Resveratrol + Curcumin) (Group A), treated with a daily oral dose of 500 mg of Resveratrol and 500 mg of Curcumin, and 20 to the control group treated with placebo (Group B). RESULTS: Significant differences were found in the body composition of the patients between both groups. There was a significant difference in Body Mass Index (BMI) values (p = 0.002), fat percentage (p = 0.007), muscle mass (p = 0.01) bone mass (p = 0.01), as well as in the score of the subjective global evaluation (p = 0.03). Also differences were found between the basal and final serum levels of Triglycerides (TG) (p = 0.01), VLDL (p = 0.003). A significant decrease in the levels of serum ferritin (2003.69 ± 518.73 vs 1795.65 ± 519.00 ng/mL; p = 0.04). Nor were significant differences observed between the baseline and the final Thiobarbituric Acid Reactive Substances (TBARS) values (70.45 ± 69.21 vs 50.19 ± 32.62, p = 0.24). The same results was obtained for carbonyl values (2.67 ± 0.75 vs 2.50 ± 0.85; p = 0.50). DISCUSSION: The present study is the first assay on patients with chronic kidney disease and iron overload that demonstrates the beneficial effects of combined supplementation with Curcumin and Resveratrol on muscle and bone mass. There was a significant decrease in circulating levels of ferritin, to finding that remarkably novel.
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Antiinflamatorios no Esteroideos/administración & dosificación , Antioxidantes/administración & dosificación , Curcumina/administración & dosificación , Suplementos Dietéticos , Sobrecarga de Hierro/tratamiento farmacológico , Diálisis Renal , Insuficiencia Renal Crónica/tratamiento farmacológico , Resveratrol/administración & dosificación , Adulto , Antiinflamatorios no Esteroideos/farmacología , Densidad Ósea/efectos de los fármacos , Curcumina/farmacología , Método Doble Ciego , Femenino , Ferritinas , Humanos , Masculino , Persona de Mediana Edad , Músculos/efectos de los fármacos , Resveratrol/farmacología , Triglicéridos/sangreRESUMEN
Differentiated cells telomere length is an indicator of senescence or lifespan; however, in peripheral blood leukocytes the relative shortening of the telomere has been considered as a biological marker of aging, and lengthening telomere as an associated risk to cancer. Individual's age, type of tissue, lifestyle, and environmental factors make telomere length variable. The presence of environmental carcinogens such as arsenic (As) influence as causal agents of these alterations, the main modes of action for As described are oxidative stress, reduction in DNA repair capacity, overexpression of genes, alteration of telomerase activity, and damage to telomeres. The telomeres of leukocytes resulting a finite capacity of replication due to the low or no activity of the telomerase enzyme, therefore, elongation telomere in this kind of cells is a potential biological marker associated with the development of chronic diseases and carcinogenesis.
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Background. Increased oxidative stress is a well described feature of patients in hemodialysis. Their need for multiple blood transfusions and supplemental iron causes a significant iron overload that has recently been associated with increased oxidation of polyunsaturated lipids and accelerated aging due to DNA damage caused by telomere shortening. Methods. A total of 70 patients were evaluated concomitantly, 35 volunteers with ferritin levels below 500 ng/mL (Group A) and 35 volunteers with ferritin levels higher than 500 ng/mL (Group B). A sample of venous blood was taken to extract DNA from leukocytes and to measure relative telomere length by real-time PCR. Results. Patients in Group B had significantly higher plasma TBARS (p = 0.008), carbonyls (p = 0.0004), and urea (p = 0.02) compared with those in Group A. Telomeres were significantly shorter in Group B, 0.66 (SD, 0.051), compared with 0.75 (SD, 0.155) in Group A (p = 0.0017). We observed a statistically significant association between relative telomere length and ferritin levels (r = -0.37, p = 0.001). Relative telomere length was inversely related to time on hemodialysis (r = -0.27, p = 0.02). Conclusions. Our findings demonstrate that iron overload was associated with increased levels of oxidative stress and shorter relative telomere length.
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Sobrecarga de Hierro/etiología , Fallo Renal Crónico/complicaciones , Estrés Oxidativo , Adulto , Envejecimiento Prematuro , Ecocardiografía , Femenino , Ferritinas/análisis , Humanos , Sobrecarga de Hierro/metabolismo , Fallo Renal Crónico/metabolismo , Fallo Renal Crónico/patología , Leucocitos/citología , Leucocitos/metabolismo , Masculino , Malondialdehído/sangre , Persona de Mediana Edad , Carbonilación Proteica , Reacción en Cadena en Tiempo Real de la Polimerasa , Diálisis Renal , Telómero/genética , Acortamiento del Telómero , Urea/sangreRESUMEN
BACKGROUND: Recently, a direct correlation with telomere length, proliferative potential and telomerase activity has been found in the process of aging in peripheral blood cells. The objective of the study was to evaluate telomere length and proliferative potential in peripheral blood mononuclear cells (PBMCs) after stimulation with Concanavalin A (ConA) of young adults compared with older adults. METHODS: Blood samples were obtained from 20 healthy young males (20-25 years old) (group Y) and 20 males (60-65 years old) (group O). We compared PBMC proliferation before and after stimulation with ConA. DNA was isolated from cells separated before and after culture with ConA for telomeric measurement by real-time polymerase chain reaction. RESULTS: In vitro stimulation of PBMCs from young subjects induced an increase of telomere length as well as a higher replicative capacity of cell proliferation. Samples from older adults showed higher loss of telomeric DNA (p = 0.03) and higher levels of senescent (≤6.2 kb) telomeric DNA (p = 0.02) and displayed a marked decrease of proliferation capacity. Viability cell counts and CFSE tracking in 72-h-old cell cultures indicated that group O PBMCs (CD8+ and CD4+ T cells) underwent fewer mitotic cycles and had shorter telomeres than group Y (p = 0.04). CONCLUSIONS: Our findings confirm that telomere length in older-age adults is shorter than in younger subjects. After stimulation with ConA, cells are not restored to the previous telomere length and undergo replicative senescence. This is in sharp contrast to the response observed in young adults after ConA stimulation where cells increase in telomere length and replicative capacity. The mechanisms involved in this phenomenon are not yet clear and merit further investigation.
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Envejecimiento/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Concanavalina A/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Homeostasis del Telómero/efectos de los fármacos , Adulto , Anciano , Envejecimiento/fisiología , Células Cultivadas , Humanos , Leucocitos Mononucleares/fisiología , Masculino , Persona de Mediana Edad , Homeostasis del Telómero/fisiología , Adulto JovenRESUMEN
AIM: To analyze the presence of Y chromosome microdeletions in males of Mexican couples with idiopathic recurrent pregnancy losses (RPL). METHODS: Seventy-one males from couples with RPL and 66 fertile males as controls were studied. DNA was isolated from peripheral lymphocytes and used to run multiplex polymerase chain reactions. Regions AZFa (sY84, sY86), AZFb (sY127, sY134) and AZFc (sY254, sY255) of the Y chromosome were analyzed according to valid guidelines recommended by the European Academy of Andrology and the European Molecular Genetics Quality Network. Also, the sequence tagged sites (STSs): DYS262 (sY67), DYS220 (sY129), DYF85S1 (sY150), DYF86S1 (sY152) and DYF87S1 (sY153) were included in order to analyze STSs previously reported as deleted. A power analysis to support our simple size was performed. RESULTS: Results show an absence of Y chromosome microdeletions in males of couples with RPL and controls with an acceptable statistical power. CONCLUSION: The study did not show an association of recurrent pregnancy loss and Y chromosome microdeletions in Mexican male partners. Based on the results, the study of Y chromosome microdeletions in couples with RPL is not considered clinically relevant.
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Aborto Habitual/etiología , Trastornos de los Cromosomas Sexuales del Desarrollo Sexual/fisiopatología , Adulto , Deleción Cromosómica , Cromosomas Humanos Y/genética , Composición Familiar , Femenino , Pruebas Genéticas , Humanos , Infertilidad Masculina , Masculino , México , Persona de Mediana Edad , Embarazo , Aberraciones Cromosómicas Sexuales , Trastornos de los Cromosomas Sexuales del Desarrollo Sexual/diagnóstico , Trastornos de los Cromosomas Sexuales del Desarrollo Sexual/genética , Adulto JovenRESUMEN
BACKGROUND: Intracytoplasmic sperm injection (ICSI) is highly effective for the control of male factor infertility. The sperm selected for ICSI may have structural abnormalities undetectable to 400x as nuclear vacuoles, decreasing rates of pregnancy and implantation. Recent studies show that with intracytoplasmic morphologically selected sperm injection (IMSI), at higher magnification (> 6,600x), increases pregnancy and implantation rates in patients with repeated failure to ICSI. OBJECTIVE: To compare the results of the injection of selected motile sperm organelle morphology examination (MSOME) for IMSI, instead of the use of ICSI in patients with repeated failure to ICSI. PATIENTS AND METHOD: Prospective, observational cohort study. Since February 1, 2010 was administered IMSI to couples with at least two failed cycles of ICSI, and analyzed the first 30 cycles in patients under 38 years of good ovarian reserve. This study group was compared with the last 30 cycles of ICSI performed before that date, in patients with similar clinical characteristics. The IMSI was performed with a magnification of 7,676 increases for evaluation and sperm selection. RESULTS: The groups had similar clinical characteristics. The pregnancy rate with IMSI was better than with ICSI (63 vs. 50%), the difference was not significant for the size of the sample, although the trend is clear and clinically significant in favor to IMSI. The implantation rate with IMSI (44.8%) showed statistically significant differences vs. ICSI (29.7%). No significant differences in abortion rates. CONCLUSIONS: IMSI significantly improves the implantation rate in patients with repeated failure to ICSI.
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Inyecciones de Esperma Intracitoplasmáticas/métodos , Espermatozoides/ultraestructura , Adulto , Distinciones y Premios , Separación Celular , Estudios de Cohortes , Implantación del Embrión , Femenino , Ginecología , Humanos , Masculino , México , Obstetricia , Embarazo , Índice de Embarazo , Estudios Prospectivos , Espermatozoides/anomalías , Insuficiencia del TratamientoRESUMEN
OBJECTIVES: To determine whether the presence of human papillomavirus (HPV) in men is a risk factor in the development of intraepithelial cervical neoplasia in their sexual partners and to corroborate HPV frequency and type. MATERIALS AND METHODS: A case-control study was carried out in the city of Colima, Mexico, from October 2004 to September 2005. It included the male sexual partners of females presenting with intraepitheleal neoplasia and with negative cervical uterine cytology. The study was approved by the local ethics committee, and participants signed a letter of informed consent. Samples were taken from the penis with a cytobrush and were analyzed by polymerase chain reaction (PCR) with type-specific HPV consensus primers. Statistical analysis was carried out using averages, percentages, and chi-square test for association. RESULTS: Twenty-one patients and 40 controls were analyzed. Eight were excluded due to DNA degradation. Chi-square test was utilized to find association between risk factor (HPV in men) in men whose sexual partners were women with premalignant lesions and normal Papanicolaou test. There was no statistical significance; OR was 2.5, CI was 0.38-16.41, and P = 0.37 (Fisher's exact test). There was no significant difference between the two study groups. Four HPV-positive cases (19%) were obtained from the case group, and two HPV-positive cases (6%) were obtained from the control group. The six positive samples had low-grade virus. There was no association between HPV in men and the cervical intraepitheleal neoplasia of their sexual partners. CONCLUSIONS: In the present study, HPV in men was not found to be a risk factor in the development of cervical uterine lesions. The viruses that were found were low risk. The sample size employed was not large enough to be able to determine any differences between both study groups.
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Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/epidemiología , Pene/virología , Parejas Sexuales , Displasia del Cuello del Útero/patología , Neoplasias del Cuello Uterino/patología , Adulto , Estudios de Casos y Controles , Coito , Femenino , Humanos , Masculino , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/transmisión , Factores de Riesgo , Neoplasias del Cuello Uterino/virología , Displasia del Cuello del Útero/virologíaRESUMEN
In our study, we analyzed chromosomal abnormalities, Y chromosome deletions, androgen receptor CAG repeat length and their association with defective spermatogenesis in infertile Mexican men. Eighty-two infertile patients and 40 controls were screened for karyotypic abnormalities, Y chromosome microdeletions, and CAG repeats. Nine infertile males (11%) carried chromosomal abnormalities and 10 (12.2%) presented Y chromosome microdeletions. The mean CAG repeat length was 21.6 and 20.88 base pairs in idiopathic infertile males and controls, respectively. Our results suggest that chromosomal aberrations and Y-chromosomal microdeletions are related to male infertility in Mexican men. In addition, expansion of the CAG repeat segments of the androgen receptor is not correlated with male idiopathic infertility.
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Aberraciones Cromosómicas , Cromosomas Humanos Y/genética , Infertilidad Masculina/genética , Receptores Androgénicos/genética , Expansión de Repetición de Trinucleótido/genética , Adulto , Análisis Citogenético , Pruebas Genéticas , Humanos , Masculino , MéxicoRESUMEN
Objective. To investigate the possible association among MTHFR polymorfhisms, environmental factors and cervical cancer (CC) in the Mexican population. Methods. Seventy patients with CC and 89 control women were questioned about clinical data and their 677 and 1298 genotypes of MTHFR gene were analized. Results. Multipregnancies (0-2 vs. > 3, OR 2.1), an early age of first intercourse (IVS) (17 < vs. > 18 years, OR 4.3) or both factors (OR 3.5) were significantly associated with CC. MTHFR 677, 1298 polymorphisms and their combinations were not different between cases and controls. However, a significant association between pregnancies, TVS and MTHFR polymorphisms (presence of 1298C allele or 677TT genotype) was observed. The 1298C allele plus multipregnancies and IVS < 17 years, or both factors, increased 4.3, 5.3, and 11.8 times the risk for CC, respectively, while 677TT genotype changed the risk 2.0, 1.9, and 4.2 times, respectively. Conclusion. The 1298C allele increases the risk of CC strongly in women with multipregnancies and early age of IVS, while 677TT genotype has a lower risk without becoming a protection factor.
Objetivo. Buscar la asociación entre polimorfismos de la enzima metilentetrahidrofolato reductasa (MTHFR), factores ambientales y cáncer cérvico-uterino (CaCU) en mujeres del noreste de México. Métodos. Setenta pacientes con CaCU y 89 mujeres controles se sometieron a un interrogatorio clínico y a genotipificación de los polimorfismos 677C -> T y 1298A -> C del gen MTHFR. Resultados. La multigestación (0-2 vs.> 3, OR 2.1), un temprano inicio de vida sexual (IVS) (17 < vs. > 18 años, OR 4.3) o la combinación de ambos factores (OR 3.5), estuvieron asociados significativamente al CaCU. Los polimorfismos de MTHFR 677, 1298 y sus combinaciones no fueron diferentes entre casos y controles. Sin embargo, se observó una interacción significativa entre las gestaciones, el IVS y los polimorfismos de MTHFR (presencia del alelo 1298C o del genotipo 677TT). El alelo 1298C combinado con multigestación, con un IVS < 17 años, o con ambos factores, incrementó el riesgo para CaCU en 4.3, 5.3 y 11.8 veces, respectivamente, en tanto que el genotipo 677TT modificó este riesgo a 2.0, 1.9, y 4.2 veces, respectivamente. Conclusión. El alelo 1298C incrementa considerablemente el riesgo para CaCU en mujeres multigestas y con un IVS temprano, en tanto que el genotipo 677TT disminuye este riesgo, pero sin llegar a convertirse en un factor protector.
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Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Embarazo , Coito , /genética , Paridad , Polimorfismo Genético , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/genética , Factores de Edad , MéxicoRESUMEN
OBJECTIVE: To investigate the possible association among MTHFR polymorfhisms, environmental factors and cervical cancer (CC) in the Mexican population. METHODS: Seventy patients with CC and 89 control women were questioned about clinical data and their 677 and 1298 genotypes of MTHFR gene were analized. RESULTS: Multipregnancies (0-2 vs. > or = 3, OR 2.1), an early age of first intercourse (IVS) (17 < or = vs. > or = 18 years, OR 4.3) or both factors (OR 3.5) were significantly associated with CC. MTHFR 677, 1298 polymorphisms and their combinations were not different between cases and controls. However, a significant association between pregnancies, IVS and MTHFR polymorphisms (presence of 1298C allele or 677TT genotype) was observed. The 1298C allele plus multipregnancies and IVS < or = 17 years, or both factors, increased 4.3, 5.3, and 11.8 times the risk for CC, respectively, while 677TT genotype changed the risk 2.0, 1.9, and 4.2 times, respectively. CONCLUSION: The 1298C allele increases the risk of CC strongly in women with multipregnancies and early age of IVS, while 677TT genotype has a lower risk without becoming a protection factor.
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Coito , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Paridad , Polimorfismo Genético , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/genética , Adulto , Factores de Edad , Anciano , Femenino , Humanos , México , Persona de Mediana Edad , EmbarazoRESUMEN
OBJECTIVES: To study the influence of the estrogen receptor-alpha (ER-alpha) genotypes (PvuII and XbaI polymorphisms) on symptoms and bone density. METHODS: We recruited 177 post-menopausal women to register hot flashes, vaginal dryness, depression, anxiety, sleep alterations, and serum hormones (FSH, LH, estrone, and estradiol). Bone mineral density (BMD) was measured with a radiographic method, correcting with an external reference. ER-alpha genotyping was carried out by PCR. RESULTS: Scores for vaginal dryness were lower for the xx (P = 0.003), and pp genotypes (P = 0.006). Hot flashes were lower for the Pp (P = 0.006) genotype. FSH circulating levels were lower for Xx genotype (P = 0.036). The factors associated with BMD were estrone (P > 0.000001), estradiol (P = 0.0035) and XbaI (P = 0.035). Vaginal dryness, was associated with PvuII and XbaI polymorphisms (P = 0.037 and P = 0.039). Depression was associated with log(estrone) (P = 0.011), schooling (negatively, P = 0.012), and marginally with BMI (P = 0.066). Sleep alterations correlated with log(estrone) (P = 0.014) and marginally with years since menopause (P = 0.046). Anxiety correlated with schooling (negatively, P = 0.006) and age (p = 0.015), and hot flashes with schooling (negatively, P = 0.014). BMD was associated with log(estrone) (p < 0.000001), estradiol (negatively, P = 0.0036), and marginally with XbaI (P = 0.036). CONCLUSIONS: In post-menopausal women, the ER-alpha polymorphism was associated with vaginal dryness, and hot flashes but not with other physical or emotional symptoms. Extraglandular estrogen production, and diverse molecular factors related to estrogen action may play an important role in this process.
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Receptor alfa de Estrógeno/genética , Polimorfismo Genético/genética , Posmenopausia/genética , Ansiedad/genética , Densidad Ósea/genética , Estudios Transversales , Depresión/sangre , Depresión/genética , Escolaridad , Estradiol/sangre , Estrona/sangre , Femenino , Hormona Folículo Estimulante/sangre , Marcadores Genéticos , Genotipo , Sofocos/genética , Humanos , Hormona Luteinizante/sangre , Persona de Mediana Edad , Osteoporosis Posmenopáusica/sangre , Osteoporosis Posmenopáusica/genética , Reacción en Cadena de la Polimerasa , Análisis de Regresión , Trastornos del Sueño-Vigilia/genética , Encuestas y Cuestionarios , Vagina/patologíaRESUMEN
Cancer is considered a genetic disease, being classified as an accumulative somatic disorder aside of the Mendelian diseases, the chromosomopaties and the multifactorial diseases. It has been demonstrated in several human cancers that specific mutations in some genes are related to hystopathologic features and tumor progression. Thereby, mutations represent potentially valuable markers in disease-stage detection and evaluation. Mutations associated with neoplasia development and evolution are very valuable, and the related genes are classified as: oncogenes, tumor suppressing genes, DNA repairing genes and cell cycle regulator genes. The factability to determine and characterize these genes and relate them with one or several steps of tumorogenesis, makes them molecular markers that let us predict risk, make an early diagnosis, confirm a diagnosis, establish prognosis, guide the therapy and determine resistance to treatments. Molecular methods used today for analysis of this markers offer great advantages: they are vary sensitive, use a small sample, are fast, can be easily automated, are easily interpreted, allows quantitations and, very importantly, they become cheaper when a large quantity of samples are handled. In this review we mention some types of cancers and molecular methods that can be used to take advantage of their biomarkers.
Asunto(s)
Neoplasias/diagnóstico , Oncogenes , Biomarcadores de Tumor/genética , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Reparación del ADN/genética , Femenino , Genes Supresores de Tumor , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Masculino , Mutación , Proteínas de Neoplasias/análisis , Proteínas de Neoplasias/genética , Neoplasias/genética , Neoplasias/terapia , Síndromes Neoplásicos Hereditarios/diagnóstico , Síndromes Neoplásicos Hereditarios/genética , Papillomaviridae/genética , Papillomaviridae/patogenicidad , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/virología , Proto-Oncogenes , Infecciones Tumorales por Virus/genética , Infecciones Tumorales por Virus/virología , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/virologíaRESUMEN
UNLABELLED: Identifying the genetic causes of male infertility is very important, considering they account for 30-50% of reproductive problems among couples. Genetic abnormalities, among which Y chromosome microdeletions are found, are commonly detected in patients with non-obstructive azoospermia (0-4.3%). Most of these patients are eligible for intracytoplasmic sperm injection (ICSI) and this genetic defect can be inherited by male children. OBJECTIVE: Determining the prevalence of microdeletions in the Y chromosome in a group of Mexican patients presenting azoospermia and oligospermia, under treatment in the Infertility Clinics. MATERIALS AND METHODS: This study included 52 infertile men (cases): 36 with non-obstructive azoospermia, and 16 with oligospermia; and 50 men (controls) whose fertility had been validated. The genomic DNA of each individual was obtained from his EDTA and heparin treated blood, and the corresponding karyotype determined. The karyotype was analyzed using G banding techniques. Eighteen markers (STS) corresponding to the chromosome Y long arm (AZFa, b, c, and d zones) were amplified in each DNA sample in all cases--azoospermic, oligospermic and controls--using the PCR method. RESULTS: No chromosomal alterations were detected in the patients, and no Y chromosome microdeletions were detected in control cases. Five azoospermic patients (13.9%) presented microdeletions corresponding to the AZFb, c, and d zones, while no microdeletions were found in oligospermic patients. The frequency of microdeletions found in this study is very similar to that reported for other populations. CONCLUSIONS: This research not only reports the frequency of microdeletions in the Y chromosome in our population, but also contributes to the integration of a DNA bank for patients with idiopathic male infertility, which will be of great use in the search for the causes of this affection.
Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Y/genética , Infertilidad Masculina/genética , Adulto , Estudios de Casos y Controles , ADN/análisis , Humanos , Masculino , Reacción en Cadena de la PolimerasaRESUMEN
Introducción: la ingesta adecuada de folatos puede reducir el riesgo para cáncer de colon. La enzima metilentetrahidrofolato reductasa (MTHFR) juega un papel importante en el metabolismo del folato. El papel de la mutación 677T del gen MTHFR en el riesgo del cáncer de colon es controversial. Recientemente se reportó que la población mexicana presenta una de las frecuencias alélicas más altas del mundo para esta mutación, por lo que resulta interesante analizar si ésta influye en el riesgo de cáncer colorrectal en nuestra población. Objetivo: determinar la frecuencia de la mutación 677T del gen MTHFR en un grupo de pacientes con cáncer de colorrectal y adenomas vs. un grupo control en una muestra de la población en el noreste de México. Método: se procesaron 74 muestras de cáncer colorrectal, 32 adenomas y 110 muestras de controles apareados por edad y sexo. Se realizó extracción de DNA y análisis de la mutación 677T mediante PCR-RFLPs. Resultados: al comparar sujetos portadores de la mutación (homocigotos T/T y heterocigotos C/T) vs. portadores de alelos normales (C/C) se obtiene un riesgo relativo de 1.81 (IC 95 por ciento 0.97 a 3.3), con ? 2 = 3.5 y p = 0.06. Conclusiones: los individuos portadores de la mutación presentan una tendencia hacia un riesgo aumentado para cáncer de colon, lo que sería congruente con el concepto que la deficiencia de folatos contribuye con la patogenia del cáncer colorrectal. La carencia de significancia estadística en este reporte se puede explicar por el tamaño de muestra.