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Objetivo: describir la crisis, funcionalidad y tipología familiar en pacientes con cáncer de mama. Métodos: estudio transversal analítico, se realizó entre agosto y diciembre de 2021. La muestra fue de 250 pacientes con cáncer de mama que cumplieron los criterios de selección. La presencia de crisis familiares se determinó con el test de Holmes-Rahe. La funcionalidad familiar se valoró con la Escala de Evaluación de Adaptabilidad y Cohesión Familiar iii. La tipología familiar se determinó con base en su conformación. Realizamos estadística descriptiva e inferencial. Para el análisis bivariado se utilizó razón de momios, χ2 de Pearson y U de Mann-Whitney con intervalos de confianza de 95% (p

Objective: to describe the crisis, functionality and family typology in patients with breast cancer. Methods: Analytical cross-sectional study, conducted between August and December 2021. The sample consisted of 250 patients with breast cancer who met the selection criteria. The presence of family crises was determined with the Holmes-Rahe test. Family functionality was assessed with the Adaptability and Family Cohesion Evaluation Scale iii. The family typology was determined based on its conformation. We perform descriptive and inferential statistics. Odds ratio, Pearson’s χ2 and Mann-Whitney U with 95% confidence intervals (p

IntroductionOver the years, the Hispanic population living in the United States has consistently shown high incidence rates of childhood acute leukemias (AL). Similarly, high AL incidence was previously observed in Mexico City (MC). Here, we estimated the AL incidence rates among children under 15 years of age in MC during the period 2010–2017.MethodsThe Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia conducted a study gathering clinical and epidemiological information regarding children newly diagnosed with AL at public health institutions of MC. Crude age incidence rates (cAIR) were obtained. Age-standardized incidence rates worldwide (ASIRw) and by municipalities (ASIRm) were calculated by the direct and indirect methods, respectively. These were reported per million population ResultsA total of 903 AL cases were registered. The ASIRw was 63.3 (cases per million) for AL, 53.1 for acute lymphoblastic leukemia (ALL), and 9.4 for acute myeloblastic leukemia. The highest cAIR for AL was observed in the age group between 1 and 4 years (male: 102.34 and female: 82.73). By immunophenotype, the ASIRw was 47.3 for B-cell and 3.7 for T-cell. The incidence did not show any significant trends during the study period. The ASIRm for ALL were 68.6, 66.6 and 62.8 at Iztacalco, Venustiano Carranza and Benito Juárez, respectively, whereas, other municipalities exhibited null values mainly for AML.ConclusionThe ASIRw for childhood AL in MC is among the highest reported worldwide. We observed spatial heterogeneity of rates by municipalities. The elevated AL incidence observed in Mexican children may be explained by a combination of genetic background and exposure to environmental risk factors.

ETV6::RUNX1 is a genetic rearrangement of good prognosis in children with acute lymphoblastic leukemia (ALL). In Mexico, its prevalence is low in comparison with Caucasian populations. We developed a novel TaqMan one-step RT-qPCR approach to assess the prevalence of four genetic rearrangements in a cohort of Hispanic children with ALL from Mexico City. The prevalence of common fusion gene transcripts was as follows: TCF3::PBX1 7.7%; BCR::ABL1p190 3.3%; and KMT2A::AFF1 2.8%, and ETV6::RUNX1was observed with low prevalence (10.5%) in comparison to that reported for developed countries. This is consistent with previous findings on Mexican children with ALL and similar to those reported on children from Hispanic populations. The confirmation of a low prevalence of ETV6::RUNX1 in children of a Hispanic origin represents an advancement in the description of genetic factors of ALL in these populations.

The distribution ofWe retrospectively analyzed the presence ofThe overall frequency of the fusion genes was 50.7%;The pediatric population of Mexico City with AML had frequencies of

In Mexico, the incidence of acute myeloid leukemia (AML) has increased in the last few years. Mortality is higher than in developed countries, even though the same chemotherapy protocols are used. CCAAT Enhancer Binding Protein Alpha (To identify the mutational landscape of theDNA was extracted from bone marrow aspirates at diagnosis. Targeted massive parallel sequencing ofCEBPA mutational profiles in Mexican pediatric AML patients and their clinical implications were evaluated for the first time. The frequency of

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most frequent pediatric cancer worldwide. Despite improvements in treatment regimens, approximately 20% of the cases cannot be cured, highlighting the necessity for identifying new biomarkers to improve the current clinical and molecular risk stratification schemes. We aimed to investigate whetherA nested case-control study including Mexican children with BCP-ALL was conducted.A lower expression ofOur findings suggest that

The aims of the present study were to optimize the detection of common fusion gene transcripts associated with childhood B-ALL prognosis through the development and validation of a one-step RT-qPCR assay and to identify the prevalence of these genes in a cohort of pediatric patients attended in public hospitals in Mexico City. The one-step RT-qPCR assay was sensitive, specific, easy to use, fast and cost efficient. The standard curves were linear, with amplification efficiencies between 97-107%; coefficients of variation were 2.1-3.0% in reproducibility and 2.6-3.8% in repeatability, with agreement between two different laboratories. The prevalence of fusion gene transcripts was ETV6-RUNX1, 10.3%; TCF3-PBX1, 7.5%; BCR-ABL1p190, 3.6%; and KMT2A-AFF1, 2.8%. The prevalence of the ETV6-RUNX1 fusion was low, consistent with the findings in Hispanics. The KMT2A-AFF1 fusion was not exclusively present in infants, as we also found it in patients 4-16 years of age, in whom it was related to a poor prognosis. TCF3-PBX1 patients were associated with an intermediate outcome. The present study highlights the importance of the detection of common genetic fusions in Mexican children with ALL, taking into account that some have molecular subtypes associated with a poor prognosis.

Background Mexico City has one of the highest incidences and mortality rates of acute lymphoblastic leukemia (ALL) in the world and a high frequency of early relapses (17%) and early mortality (15%). Otherwise, childhood overweight and obesity are reaching epidemic proportions. They have been associated with poor outcomes in children with ALL. The aim of present study was to identify if overweight and obesity are predictors of early mortality and relapse in Mexican children with ALL. Methods A multicenter cohort study was conducted. ALL children younger than 15 years old were included and followed-up during the first 24 months after diagnosis. Overweight and obesity were classified according World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) criteria. Early mortality and early relapses were the main outcomes. Results A total of 1070 children were analyzed. Overweight/obesity at diagnosis were predictors of early mortality (WHO: HR = 1.4, 95%CI:1.0–2.0; CDC: HR = 1.6, 95%CI:1.1–2.3). However, no associations between overweight (WHO: HR = 1.5, 95%CI:0.9–2.5; CDC: HR = 1.0; 95% CI:0.6–1.6) and obesity (WHO: HR = 1.5, 95%CI:0.7–3.2; CDC: HR = 1.4; 95%CI:0.9–2.3) with early relapse were observed. Conclusions Overweight and obese patients embody a subgroup with high risk of dying during leukemia treatment. Electronic supplementary material The online version of this article (10.1186/s12885-019-5878-8) contains supplementary material, which is available to authorized users.

Background: Acute myeloid leukemia (AML) is the second most frequent leukemia in childhood. The FLT3 gene participates in hematopoietic stem cell proliferation. FLT3 mutations are recurrent in AML and influence prognosis. In Mexican pediatric AML patients, FLT3 mutational profile, and their clinical impact have not been evaluated. Aim of the study: This study aimed to identify the profile of FLT3 mutations in pediatric patients with de novo AML and to assess their possible influence on overall survival (OS) and other clinical features. Methods: Massive parallel target sequencing of FLT3 was performed in 80 patients. Results: FLT3 mutations [internal tandem duplication (ITD) or tyrosine kinase domain (TKD)] were identified in 24% of them. OS was significantly lower in FLT3POS cases than in FLT3NEG (p = 0.03). The average OS for FLT3POS was 1.2 vs. 2.2 years in FLT3NEG. There were no significant differences in the children's sex, age, percentage of blasts in bone marrow aspirate, or white blood cell count in peripheral blood at diagnosis between both groups. No differences were identified stratifying by the mutational load (high > 0.4) or type of mutation. The negative effect of FLT3 mutations was also observed in patients with acute promyelocytic leukemia (APL). Conclusions: FLT3 mutational profile is described in Mexican pediatric AML patients for the first time. Mutated FLT3 negatively impacts the outcome of AML patients, even considering the APL group. The clinical benefit from treatment with tyrosine kinase inhibitors in the FLT3POS pediatric patients needs to be assessed in clinical trials. FLT3 testing may contribute to better risk stratification in our pediatric AML patients.

Objective To determine the frequency and type of pleuropulmonary complications and their predictors in the first thirty postoperative days of patients undergoing surgery without cardiopulmonary bypass. Methods A retrospective cohort study was carried out between January 2013 and December 2014. It included all patients with congenital heart disease who underwent cardiac surgery using a sternal or thoracic approach, without cardiopulmonary bypass with a registered admission to a Neonatal or Paediatric Intensive Care. The frequency of events of pleuropulmonary complications and logistic regression analysis was performed, and the adjusted odds ratio (OR) and confidence intervals at 95% (95% CI) were calculated. Results A total of 139 patients were included. The frequency of pleuropulmonary complications was 42.4% (N=59), and the most frequent types were atelectasis (28 events), ventilator-associated pneumonia (24 events), pneumothorax (20 events), with more than one complication per patient occasionally being found. Significant risk factors were cyanogenic congenital heart disease (OR=3.58, 95% CI: 1.10-7.50, P=.001), thoracotomy approach (OR=1.46, 95% CI: 1.18-1.12, P=.008), and an emergency surgical event (OR=3.46, 95% CI: 1.51-7.95, P=.002). Conclusions The main pleuropulmonary complication was atelectasis, which is consistent with that reported in the international literature. Patients with any of the predictors identified in the present study should be closely monitored in order to prevent, detect and/or treat pleuropulmonary complications in a timely manner after cardiac surgery.

Evidence showing the role of long non-coding RNAs (lncRNAs) in leukemogenesis have emerged in the last decade. It has been proposed that these genes can be used as diagnosis and/or prognosis biomarkers in childhood acute lymphoblastic leukemia (ALL). To know if lncRNAs are associated with early relapse and early mortality, a microarray-based gene expression analysis in children with B-lineage ALL (B-ALL) was conducted. Cox regression analyses were performed. Hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated. LINC00152 and LINC01013 were among the most differentially expressed genes in patients with early relapse and early mortality. For LINC00152 high expression, the risks of relapse and death were HR: 4.16 (95% CI: 1.46&ndash, 11.86) and HR: 1.99 (95% CI: 0.66&ndash, 6.02), respectively, for LINC01013 low expression, the risks of relapse and death were HR: 3.03 (95% CI: 1.14&ndash, 8.05) and HR: 6.87 (95% CI: 1.50&ndash, 31.48), respectively. These results were adjusted by NCI risk criteria and chemotherapy regimen. The lncRNA&ndash, mRNA co-expression analysis showed that LINC00152 potentially regulates genes involved in cell substrate adhesion and peptidyl&ndash, tyrosine autophosphorylation biological processes. The results of the present study point out that LINC00152 could be a potential biomarker of relapse in children with B-ALL.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children around the globe. Mexico City has one of the highest incidence rates of childhood leukemia worldwide with 49.5 cases per million children under the age of 15 which is similar to that reported for Hispanic populations living in the United States. In addition, it has been noted a dismal prognosis in Mexican and Hispanic ALL pediatric population. Although ALL, like cancer in general, has its origins in endogenous, exogenous, and genetic factors, several studies have shown that the immune system also plays a deterministic role in cancer development. Among various elements of the immune system, T lymphocytes and NK cells seem to dominate the immune response against leukemia. The aim of the present study was to perform a phenotypic and functional characterization of NK cells in ALL Mexican children at the moment of diagnosis and before treatment initiation. A case-control study was conducted by the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia (MIGICCL). 41 cases were incident ALL children younger than 17 years old and residents of Mexico City. 14 controls were children without leukemia, matched by age and sex with cases. NK cell function was evaluated by degranulation assays towards K562 cells and SLAM-associated protein (SAP) expression was measured by intracellular staining. All assays were performed using peripheral blood mononuclear cells from controls and patients. The results indicate that NK mediated cytotoxicity, measured by CD107a degranulation assays in response to K562 cells, was reduced in ALL patients compared to controls. Interestingly, an impaired NK cell killing of target cells was not equally distributed among ALL patients. In contrast to patients classified as high-risk, standard-risk patients did not display a significant reduction in NK cell-mediated cytotoxicity. Moreover, patients presenting a leukocyte count ≥ 50,000xmm3 displayed a reduction in NK-cell mediated cytotoxicity and a reduction in SAP expression, indicating a positive correlation between a reduced SAP expression and an impaired NK cell-mediated citotoxicity. In the present study it was observed that unlike patients with standard-risk, NK cells from children presenting high-risk ALL, harbor an impaired cytotoxicity towards K562 at diagnosis. In addition, NK cell function was observed to be compromised in patients with a leukocyte count ≥50,000xmm3, where also it was noticed a decreased expression of SAP compared to patients with a leukocyte count

In Mexico, due to the high rates of diabetes, overweight, and obesity, there has also been noted an increased newborn weight, which may be contributing to the elevated incidence rate of childhood acute leukemia (AL). We conducted a case–control study in public hospitals of Mexico City aimed to know whether a greater weight at birth is associated with a higher risk of developing leukemia. We included incident cases with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) diagnosed between 2010 and 2015. Controls were frequency‐matched to the cases by age, sex, and health institution. Logistic regression analysis was performed adjusting risks by child's sex, overcrowding index, birth order, and mother's age at the time of pregnancy. Adjusted odds ratios (aORs) and 95% confidence intervals were calculated. A total of 1455 cases and 1455 controls were included. An evident association between ALL and child's birthweight ≥2500 g was found (aOR 2.06; 95% CI: 1.59, 2.66) and also, in those with birthweight ≥3500 g (aOR 1.19; 95% CI: 1.00, 1.41). In AML patients with birthweight ≥2500 g and ≥3500 g, an aOR of 1.77 (95% CI: 1.07, 2.94) and 1.42 (95% CI: 1.03–1.95) was observed, respectively. No association was noticed with either type of AL and a birthweight ≥4000 g. To sum up, we found a moderate association between not having a low birthweight and an increased risk of acute leukemias. Birthweight ≥3500 g was also a risk factor for both types of leukemia. This suggests that a greater birthweight may increase the risk of acute leukemias in Mexican children.

To determine the frequency and type of pleuropulmonary complications and their predictors in the first thirty postoperative days of patients undergoing surgery without cardiopulmonary bypass.A retrospective cohort study was carried out between January 2013 and December 2014. It included all patients with congenital heart disease who underwent cardiac surgery using a sternal or thoracic approach, without cardiopulmonary bypass with a registered admission to a Neonatal or Paediatric Intensive Care. The frequency of events of pleuropulmonary complications and logistic regression analysis was performed, and the adjusted odds ratio (OR) and confidence intervals at 95% (95% CI) were calculated.A total of 139 patients were included. The frequency of pleuropulmonary complications was 42.4% (N=59), and the most frequent types were atelectasis (28 events), ventilator-associated pneumonia (24 events), pneumothorax (20 events), with more than one complication per patient occasionally being found. Significant risk factors were cyanogenic congenital heart disease (OR=3.58, 95% CI: 1.10-7.50, P=.001), thoracotomy approach (OR=1.46, 95% CI: 1.18-1.12, P=.008), and an emergency surgical event (OR=3.46, 95% CI: 1.51-7.95, P=.002).The main pleuropulmonary complication was atelectasis, which is consistent with that reported in the international literature. Patients with any of the predictors identified in the present study should be closely monitored in order to prevent, detect and/or treat pleuropulmonary complications in a timely manner after cardiac surgery.

Acute lymphoblastic leukemia is the most common type of childhood cancer worldwide. Mexico City has one of the highest incidences and mortality rates of this cancer. It has previously been recognized that chromosomal translocations are important in cancer etiology. Specific fusion genes have been considered as important treatment targets in childhood acute lymphoblastic leukemia (ALL). The present research aimed at the identification and characterization of novel fusion genes with potential clinical implications in Mexican children with acute lymphoblastic leukemia. The RNA-sequencing approach was used. Four fusion genes not previously reported were identified: CREBBP-SRGAP2B, DNAH14-IKZF1, ETV6-SNUPN, ETV6-NUFIP1. Although a fusion gene is not sufficient to cause leukemia, it could be involved in the pathogenesis of the disease. Notably, these new translocations were found in genes encoding for hematopoietic transcription factors which are known to play an important role in leukemogenesis and disease prognosis such as IKZF1, CREBBP, and ETV6. In addition, they may have an impact on the prognosis of Mexican pediatric patients with ALL, with the potential to be included in the current risk stratification schemes or used as therapeutic targets.

Background: In Mexico City, the incidence of childhood acute lymphoblastic leukemia (ALL) is one of the highest in the world; epidemiologic evidence suggests that infectious agents could be involved in the genesis of this disease. Early transmitted oncogenic retroviruses infecting lymphocytes are important candidates. Methods: PCR-based assays were used to screen viral genomic sequences of human T-cell lymphotrophic virus, type 1 (HTLV1) and mouse mammary tumor virus (MMTV)–like virus (MMTV-LV) in leukemic cells from 67 pediatric patients with ALL. Results: Viral genomic sequences were not detected in any sample by neither standard nor nested PCR. Conclusions: Because of the methodologic strictness and high statistical power of the study, these results suggest that HTLV1 and MMTV-LV are not involved in the genesis of childhood ALL in Mexican children. Impact: To our knowledge, this is the first work exploring the direct participation of HTLV1 and MMTV-LV retroviruses in childhood ALL development. Cancer Epidemiol Biomarkers Prev; 22(11); 2130–3. ©2013 AACR.

Background: Allergies have been described as protective factors against the development of childhood acute leukaemia (AL). Our objective was to investigate the associations between allergy history and the development of AL and acute lymphoblastic leukaemia (ALL) in children with Down syndrome (DS). Methods: A case–control study was performed in Mexico City. The cases (n=97) were diagnosed at nine public hospitals, and the controls (n=222) were recruited at institutions for children with DS. Odds ratios (OR) were calculated. Results: Asthma was positively associated with AL development (OR=4.18; 95% confidence interval (CI): 1.47–11.87), whereas skin allergies were negatively associated (OR=0.42; 95% CI: 0.20–0.91). Conclusion: Our findings suggest that allergies and AL in children with DS share biological and immune mechanisms. To our knowledge, this is the first study reporting associations between allergies and AL in children with DS.

Acute myeloid leukemias represent the second most common childhood leukemia subtype. In Mexico, there are few studies on descriptive epidemiology for this disease.To report acute myeloid leukemia incidence for children less than 15 years of age in the Metropolitan Area of the Valley of Mexico for a period of five years (2010-2014) and to analyze whether there are differences in the incidence of acute myeloid leukemia by regions.A descriptive study was conducted in nine public hospitals in Mexico City. The crude annual average incidence rate and adjusted average annual incidence rate were calculated.A total of 190 patients with diagnosis of de novo acute myeloid leukemia were analyzed. Male sex (57.2%) and acute myeloid leukemia-M3 subtype (25.3%) were more frequent. The adjusted average annual incidence rates for Mexico City and for the Metropolitan Area of the Valley of Mexico were 8.18 and 7.74 per million children under 15 years old, respectively.It seems that childhood acute myeloid leukemia incidence is increasing in Mexico City, which makes the identification of associated risk factors imperative.

Worldwide, acute leukaemia (AL) is the commonest type of childhood malignancy with an annual incidence of 30–50 cases per million children (Curado et al, 2007); Mexico City has one of the highest rates, at 58.4 cases per million (Mejia-Arangure et al, 2005a). Among the identified risk factors, individuals with Down syndrome (DS) below 20 years of age have 10- to 20-fold greater risk of developing AL compared with the general population (Robison, 1992; Ross et al, 2005). According to the Greaves' hypotheses, late contact with infectious agents may lead to an abnormal or aberrant immune response that favors the development of acute lymphoblastic leukaemia (ALL) (Greaves, 2005). Correspondingly, early infections have a protective effect in ALL by promoting the physiological maturation of the immune system, whereas late infections promote an excessive proliferation of the lymphocytes (McNally and Eden, 2004; Menegaux et al, 2004; Greaves, 2006; O'Connor and Boneva, 2007). Children with DS, due to their increased susceptibility to AL, provide a natural and valuable model for evaluating the interaction between the susceptibility for AL and the environment. In this study, we assessed whether breastfeeding and early infection were associated with the risk of developing AL in children with DS. Mother's milk is an important modulator of the immune response in infants because, while by providing the child with antibodies and immune cells, it can also be a source of transmission of infectious agents (MacArthur et al, 2008).

We analyzed effects of exposure to magnetic fields on the expression of acute leukemia in children with Down syndrome (who have a 20-fold higher risk of leukemia).: We performed a case-control study that included 42 children with both acute leukemia and Down syndrome as cases and 124 healthy children with Down syndrome as controls. We obtained demographic information concerning the children and took spot measurements of magnetic fields at each residence.: The odds ratio for direct measurements of magnetic fields/=6.00 mG was 3.7 (95% confidence interval = 1.05-13.1).: The association between magnetic fields and leukemia in children with Down syndrome suggests the possibility of a causal role for magnetic fields in the etiology of leukemia among a genetically susceptible subgroup of children.

Mexico has one of the highest incidences of childhood leukemia worldwide and significantly higher mortality rates for this disease compared with other countries. One possible cause is the high prevalence of gene rearrangements associated with the etiology or with a poor prognosis of childhood acute lymphoblastic leukemia (ALL). The aims of this multicenter study were to determine the prevalence of the four most common gene rearrangements [ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, andMLLrearrangements] and to explore their relationship with mortality rates during the first year of treatment in ALL children from Mexico City. Patients were recruited from eight public hospitals during 2010–2012. A total of 282 bone marrow samples were obtained at each child’s diagnosis for screening by conventional and multiplex reverse transcription polymerase chain reaction to determine the gene rearrangements. Gene rearrangements were detected in 50 (17.7%) patients.ETV6-RUNX1was detected in 21 (7.4%) patients,TCF3-PBX1in 20 (7.1%) patients,BCR-ABL1in 5 (1.8%) patients, andMLLrearrangements in 4 (1.4%) patients. The earliest deaths occurred at months 1, 2, and 3 after diagnosis in patients withMLL, ETV6-RUNX1, andBCR-ABL1gene rearrangements, respectively. Gene rearrangements could be related to the aggressiveness of leukemia observed in Mexican children.

Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood worldwide and Mexico has reported one of the highest incidence rates. An infectious etiology has been suggested and supported by epidemiological evidences; however, the identity of the involved agent(s) is not known. We considered that early transmitted lymphotropic herpes viruses were good candidates, since transforming mechanisms have been described for them and some are already associated with human cancers. In this study we interrogated the direct role of EBV, HCMV, HHV6, and HHV7 human herpes viruses in childhood ALL. Viral genomes were screened in 70 bone marrow samples from ALL patients through standard and a more sensitive nested PCR. Positive samples were detected only by nested PCR indicating a low level of infection. Our result argues that viral genomes were not present in all leukemic cells, and, hence, infection most likely was not part of the initial genetic lesions leading to ALL. The high statistical power of the study suggested that these agents are not involved in the genesis of ALL in Mexican children. Additional analysis showed that detected infections or coinfections were not associated with prognosis.

The role of infection in the etiology of leukemia was revealed for the first time more than ninety years ago through a series of cases reported by Gordon Ward in the year 1917. These cases included 1457 children with acute leukemia, but the results were inconclusive. Later, in another study by Poynton, Thursfield and Paterson, the authors reported that it was not possible to attribute the etiology of leukemia to a single infectious agent and emphasized the importance of host susceptibility in the acquirement of an infection and the development of acute leukemia.[1,2]

Down syndrome (DS), or trisomy 21, is a genetic alteration caused by the presence of an extra chromosome 21. In different parts of the world, the incidence of DS varies from 0.3 to 3.4 per 1000 births, with a ratio of 1:1000 births being reported principally in America and Europe (Canfield et al., 2006; Hassold et al., 1996; Wahab et al., 2006; Webb et al., 2007). DS is associated with cardiovascular diseases; deficiencies of the digestive, immune, and endocrine systems; hematological problems; and also early onset of Alzheimer disease (Freeman et al., 2008; Holland et al., 2000; Linabery et al., 2008; Van Cleeve & Cohen, 2006; Wiseman et al., 2009). Compared to children without this syndrome, children with DS have tento twenty-fold higher risk of developing acute leukemia (AL) (Fong & Brodeur, 1987; Malinge et al., 2009; Ross et al., 2005a; Taub, 2001); it is estimated that approximately 1–2% will develop leukemia (Hasle et al., 2000; Malinge et al., 2009; Taub, 2001). Of those children with DS who develop leukemia, 60% is classified as having acute lymphoblastic leukemia (ALL) and 40%, with acute myeloblastic leukemia (AML). Of those with AML, the most common type is M7, or acute megakaryoblastic leukemia (AMKL), found in 62% of this group of children (Hitzler & Zipursky, 2005). Approximately 10% of children with DS are born with a transitory myeloproliferative syndrome (TMS) that, in some cases, spontaneously disappears during the first few months of life; nevertheless, approximately, 20% of these children irreversibly develop AML. Children with DS have up to 500-fold higher risk of developing AMKL during the first four years (Hasle et al., 2000, 2001; Malinge et al., 2009; Zipursky, 2003). Because the high incidence of AL in children with DS is strong evidence of the participation of chromosome 21 in the development of AL, investigation has been directed toward the

BackgroundMedical research has not been able to establish whether a father's occupational exposures are associated with the development of acute leukemia (AL) in their offspring. The studies conducted have weaknesses that have generated a misclassification of such exposure. Occupations and exposures to substances associated with childhood cancer are not very frequently encountered in the general population; thus, the reported risks are both inconsistent and inaccurate. In this study, to assess exposure we used a new method, an exposure index, which took into consideration the industrial branch, specific position, use of protective equipment, substances at work, degree of contact with such substances, and time of exposure. This index allowed us to obtain a grade, which permitted the identification of individuals according to their level of exposure to known or potentially carcinogenic agents that are not necessarily specifically identified as risk factors for leukemia. The aim of this study was to determine the association between a father's occupational exposure to carcinogenic agents and the presence of AL in their offspring.MethodsFrom 1999 to 2000, a case-control study was performed with 193 children who reside in Mexico City and had been diagnosed with AL. The initial sample-size calculation was 150 children per group, assessed with an expected odds ratio (OR) of three and a minimum exposure frequency of 15.8%. These children were matched by age, sex, and institution with 193 pediatric surgical patients at secondary-care hospitals. A questionnaire was used to determine each child's background and the characteristics of the father's occupation(s). In order to determine the level of exposure to carcinogenic agents, a previously validated exposure index (occupational exposure index, OEI) was used. The consistency and validity of the index were assessed by a questionnaire comparison, the sensory recognition of the work area, and an expert's opinion.ResultsThe adjusted ORs and 95% confidence intervals (CI) were 1.69 (0.98, 2.92) during the preconception period; 1.98 (1.13, 3.45) during the index pregnancy; 2.11 (1.17, 3.78) during breastfeeding period; 2.17 (1.28, 3.66) after birth; and 2.06 (1.24, 3.42) for global exposure.ConclusionThis is the first study in which an OEI was used to assess a father's occupational exposure to carcinogenic agents as a risk factor for the development of childhood AL in his offspring. From our results, we conclude that children whose fathers have been exposed to a high level of carcinogenic agents seem to have a greater risk of developing acute leukemia. However, confounding factors cannot be disregarded due to an incomplete control for confounding.

Abstract 4301 Background: Acute lymphoblastic leukemia (ALL) is the most common type of childhood malignancy worldwide and Mexico has one of the highest reported incidence rates at 49.5 cases per million. Infections have been strongly suggested to be a causative factor for ALL; however, the identity of the agent involved is presently unknown. In many animal species, members of the Retroviridae family are responsible for leukemias. The murine mammary tumor virus (MMTV) is associated with leukemia and breast cancer in mice and has been suggested to be associated with human breast cancer. The T-cell lymphotropic virus 1 (HTLV1) is the causative factor of adult T cell leukemia. In this study, we assessed whether MMTV and HTLV1/2 are also involved in childhood ALL. Materials and methods: 95 children from four Mexican states and Mexico City with untreated B cell ALL, aged 8 months to 16 years were included in the study. Bone marrow samples were screened using conventional PCR assays. Because the mutation rate is considerably high in retroviruses, false negatives due to inadequate primer recognition are likely. To avoid that, two sets of primers targeting different regions of the retroviral genomes were used and the PCR annealing temperatures were set at ≤ 55 °C. Also, the primers used in these assays had low similarity with human endogenous retroviral sequences to exclude false positives. The sensitivity of the MMTV PCR reactions was determined with plasmid DNA containing a region of the MMTV env gene and genomic DNA from CD1 mice spleens and for HTLV1/2 with DNA from the MJ cell line. Because ALL is defined by a frequency of at least 25% of leukemic blasts, the PCR sensitivities were set to detect in samples at least this frequency of infected cells. A nested PCR was also designed to confirm negative cases. Results: None of the samples were positive to any of the retroviruses. The study's statistical power to detect one or more MMTV or HTLV1/2 positive samples from our study population (N=95) for 20%, 15% or 10% hypothesized proportions of cases with genomic integration was quite high. Conclusion: Our study does not support the involvement of MMTV or HTLV1/2 in the etiology of childhood acute lymphoblastic leukemia in samples from Mexico. Acknowledgments and funding: This work was partially funded by the Mexican Institute of Social Security through its program “Apoyo Financiero para el Desarrollo de Protocolos de Investigación en Salud en el IMSS” and by the Graduate Program of Doctor Degree in Biomedical Sciences, Medicine Faculty, National Autonomous University of Mexico, Mexico City, Mexico. Disclosures: No relevant conflicts of interest to declare.

Background Worldwide, acute leukemia is the most common type of childhood cancer. It is particularly common in the Hispanic populations residing in the United States, Costa Rica, and Mexico City. The objective of this study was to determine the incidence of acute leukemia in children who were diagnosed and treated in public hospitals in Mexico City. Methods Included in this study were those children, under 15 years of age and residents of Mexico City, who were diagnosed in 2006 and 2007 with leukemia, as determined by using the International Classification of Childhood Cancer. The average annual incidence rates (AAIR), and the standardized average annual incidence rates (SAAIR) per million children were calculated. We calculated crude, age- and sex-specific incidence rates and adjusted for age by the direct method with the world population as standard. We determined if there were a correlation between the incidence of acute leukemias in the various boroughs of Mexico City and either the number of agricultural hectares, the average number of persons per household, or the municipal human development index for Mexico (used as a reference of socio-economic level). Results Although a total of 610 new cases of leukemia were registered during 2006-2007, only 228 fit the criteria for inclusion in this study. The overall SAAIR was 57.6 per million children (95% CI, 46.9-68.3); acute lymphoblastic leukemia (ALL) was the most frequent type of leukemia, constituting 85.1% of the cases (SAAIR: 49.5 per million), followed by acute myeloblastic leukemia at 12.3% (SAAIR: 6.9 per million), and chronic myeloid leukemia at 1.7% (SAAIR: 0.9 per million). The 1-4 years age group had the highest SAAIR for ALL (77.7 per million). For cases of ALL, 73.2% had precursor B-cell immunophenotype (SAAIR: 35.8 per million) and 12.4% had T-cell immunophenotype (SAAIR 6.3 per million). The peak ages for ALL were 2-6 years and 8-10 years. More than half the children (58.8%) were classified as high risk. There was a positive correlation between the average number of persons per household and the incidence of the pre-B immunophenotype (Pearson's r, 0.789; P = 0.02). Conclusions The frequency of ALL in Mexico City is among the highest in the world, similar to those found for Hispanics in the United States and in Costa Rica.