Young Mexican Patients Research Articles

SOX9 is associated with advanced T-stages of clinical stage II colon cancer in young Mexican patients.

Colorectal cancer (CRC) is one of the most common malignancies worldwide and includes colon cancer (CC) and rectal cancer (RC). Regarding CC, the development of novel molecular biomarkers for the accurate diagnosis and prognosis, as well as the identification of novel targets for therapeutic intervention, are urgently needed. SRY-related high-mobility group box 9 (SOX9), a transcription factor, is involved in development, and has been associated with the progression of human cancer. However, its underlying clinical and functional effects in CRC have not been fully understood. Therefore, the present study aimed to evaluate the clinical and functional relevance of SOX9 expression in CC. The expression of SOX9 in tumor tissues was evaluated in 97 biopsies from Mexican patients with CC with early-stage I and II disease by immunohistochemistry (IHC). In addition, SOX9 silencing in the HCT116 cell line was performed using specific small interfering RNAs, while downregulation efficiency was verified by reverse transcription-quantitative PCR and immunofluorescence. Spheroid-formation assay was carried out using ultra-low attachment plates. The IHC results showed that SOX9 was upregulated in patients with stage II (91%) and advanced T3 stage (67%) CC. Interestingly, higher SOX9 expression was associated with clinical stage, tumor size and tumor location. Furthermore, increased SOX9 expression was found in relapsed cases with local tumors; however, it was not associated with increased survival probability. Additionally, functional analysis indicated that SOX9 silencing significantly attenuated the sphere-formation capability of HCT116 cells. The present study was the first to evaluate the expression levels of SOX9 in Mexican patients diagnosed with early-stage CC. The aforementioned findings indicated that high SOX9 expression could play an important role in tumorigenesis and be associated with advanced T-stages of clinical-stage II patients, but not with relapse-free survival.

Improving Collection of Real-World Data: The Experience of the Joven & Fuerte Prospective Cohort for Mexican Young Women With Breast Cancer

The prospective collection of clinical data can generate detailed information on heterogeneous populations. This article reviews the strengths and limitations of the collection of real-world data and provides insight into the feasibility of routine collection of high-quality evidence even in a resource-constrained setting. The acquisition of high-quality data to assess the clinical and psychosocial needs of young Mexican patients with breast cancer has been enhanced through the use of preplanned, standardized data definitions and instrumentation to provide internally and externally comparable results, optimization of data collection with web-based surveys, engagement of participants to minimize missing data, and routine review for data consistency. A similar approach by other research groups could improve the quality of real-world data and accomplish enhanced inference of information.

Identification of genetic risk factors associated with ischaemic stroke in young Mexican patients

BackgroundNumerous polymorphisms in candidate genes coding for haemostatic system proteins have been proposed as risk factors for thrombosis. MethodsWe performed a case-control study of consecutive ischaemic stroke survivors aged ≤45 years, treated at our neurology department from 2006 to 2014. Polymerase chain reaction–restriction fragment length polymorphism identified the following polymorphisms: Thr325Ile and Ala147Thr in TAFI, 4G/5G in PAI-1, PLA1/A2 in platelet glycoprotein IIb/IIIa, Glu298Asp in eNOS, and C677T in 5,10-MTHFR. A multivariate logistic regression analysis was performed to evaluate the independent risk of stroke. Results204 cases and 204 age- and sex-matched controls were included in the study. Clinical and genetic variables associated with ischaemic stroke were hypertension (P=.03), tobacco use (P=.02), and the polymorphisms Glu298Asp (genotype: P=.001, allele frequency: P=.001) and C677T (genotype: P=.01); the Ala147Thr, Thr325IIe, 4G/5G, and PLA1/A2 mutations were not associated with ischaemic stroke. The 298Asp (P=.03) and T (P=.01) alleles, hypertension (P=.03), tobacco use (P=.01) and family history of stroke (P=.04) were identified as independent risk factors. ConclusionThe polymorphisms Glu298Asp and C677T, affecting the eNOS and 5,10-MTHFR enzymes, respectively, and smoking, hypertension, and family history of stroke were associated with ischaemic stroke in young Mexican patients; this was not the case for the Thr325Ile, Ala147Thr, 4G/5G, and PLA1/A2 polymorphisms of the genes coding for fibrinolytic proteins and platelet receptors.

Breast Cancer Diagnostic Delays in Young Mexican Patients Are Associated With Lack of Suspicion by Healthcare Providers at First Presentation

Background: Breast cancer (BC) is the leading cause of cancer-related mortality in women between 20 and 40 years of age. Younger patients are more likely to be diagnosed in advanced clinical stages in comparison with their older counterparts. This has been explained by 2 possible mechanisms: 1) more aggressive tumor behavior that leads to faster cancer growth and dissemination, and 2) greater delays in confirming cancer diagnosis among younger women. However, there is conflicting evidence regarding the association between young age and a longer diagnostic interval of care. Aims: This study aimed to determine whether there is an association between the patient's age and the length of the diagnostic interval of care, and to identify the mechanisms that might explain this association. Methods: We surveyed 708 patients that received a new BC diagnosis between 06.01.16 and 05.31.17 in the 2 largest public hospitals in Mexico City for uninsured patients. All patients signed informed consent. Patients' medical files were reviewed. We gathered data on: dates for estimation of the diagnosis interval (first medical consultation and diagnosis confirmation), sociodemographic characteristics, form of BC identification (symptoms vs screening) and health service utilization variables. The 589/708 (83%) patients who identified their BC through self-detection were included in the final analysis. We adjusted Cox regression models to assess the relationship between age and the length of the diagnosis interval. Results: 110/589 (18%) participants were 40 years old or younger. Young age was significantly associated with longer diagnosis intervals of care after controlling by education, occupation, health insurance status, type of first health care services used, specialty of the first doctor consulted, first imaging study result, number of breast imaging studies, and transportation time from residence to hospital. The risk of 1 additional day between first medical consultation and diagnostic confirmation was increased by 1% for each year of less age (HR = 1.01, P = 0.003). The significant association between age and diagnosis delay was lost when adding to the model the following variables: first medical diagnostic impression (as perceived by the patient), number of health services used and number of consultations previous to arrival to the cancer hospital. Conclusion: Our results confirm that the younger a patient, the higher the risk of experiencing delays on the diagnostic interval. Additionally, these findings suggest that delays in public services available for the uninsured in Mexico are related to medical errors at first presentation and, consequently, the need of using different services and having multiple consultations before a BC diagnosis can be ascertained. To enhance earlier diagnosis it is imperative that healthcare providers are aware of the burden of BC in young women, and not automatically discard this diagnostic possibility because of young age.

Characterization of young Mexican patients with breast cancer who underwent oocyte/embryo preservation

Background: Young women represent a high proportion of breast cancer (BC) patients in Mexico and age-related special needs are not routinely addressed. The Mexican young women with breast cancer (YWBC) program “Joven & Fuerte” was created with the goal of comprehensively characterizing and assessing patients’ needs to tailor clinical interventions and supportive care.

Validation of a scale of health beliefs about type 1 diabetes for the Mexican context: HBM-T1DM

To generate a scale to measure health beliefs among Mexican adolescents and young people with type 1 diabetes (T1DM) to determine the extent to which they affect adherence to treatment and to be able to develop more effective social marketing campaigns. Based on the Health Belief Model (HBM), a scale was generated; three field tests were applied, and it was administered in two regions of Mexico to young people with type 1 diabetes.Tests of reliability, stability, convergence-discrimination and predictive validity were developed. The main predictor is perceived barriers to treatment adherence, followed by self-efficacy to disease control, susceptibility/vulnerability to disease complications and perceived benefits of treatment. This scale may be especially useful for better monitoring young Mexican patients with T1DM and prevent sequelae of disease.

Identificación de factores de riesgo genéticos asociados a la enfermedad vascular cerebral de tipo isquémico en jóvenes mexicanos

IntroductionNumerous polymorphisms in candidate genes coding for haemostatic system proteins have been proposed as risk factors for thrombosis. MethodsWe performed a case-control study of consecutive ischaemic stroke survivors aged ≤ 45 years, treated at our neurology department from 2006 to 2014. Polymerase chain reaction–restriction fragment length polymorphism identified the following polymorphisms: Thr325Ile and Ala147Thr in TAFI, 4G/5G in PAI-1, PLA1/A2 in platelet glycoprotein IIb/IIIa, Glu298Asp in eNOS, and C677T in 5,10-MTHFR. A multivariate logistic regression analysis was performed to evaluate the independent risk of stroke. Results204 cases and 204 age- and sex-matched controls were included in the study. Clinical and genetic variables associated with ischaemic stroke were hypertension (P=.03), tobacco use (P=.02), and the polymorphisms Glu298Asp (genotype: P=.001, allele frequency: P=.001) and C677T (genotype: P=.01); the Ala147Thr, Thr325IIe, 4G/5G, and PLA1/A2 mutations were not associated with ischaemic stroke. The 298Asp (P=.03) and T (P=.01) alleles, hypertension (P=.03), tobacco use (P=.01) and family history of stroke (P=.04) were identified as independent risk factors. ConclusionsThe polymorphisms Glu298Asp and C677T, affecting the eNOS and 5,10-MTHFR enzymes, respectively, and smoking, hypertension, and family history of stroke were associated with ischaemic stroke in young Mexican patients; this was not the case for the Thr325Ile, Ala147Thr, 4G/5G, and PLA1/A2 polymorphisms of the genes coding for fibrinolytic proteins and platelet receptors.

"Joven & Fuerte": Program for Young Women with Breast Cancer in Mexico -Initial Results.

Despite the high rates of breast cancer among young Mexican women, their special needs and concerns have not been systematically addressed. To fulfill these unsatisfied demands, we have developed "Joven & Fuerte: Program for Young Women with Breast Cancer in Mexico," the first program dedicated to the care of young breast cancer patients in Latin America, which is taking place at the National Cancer Institute of Mexico and the two medical facilities of the Instituto Tecnológico y de Estudios Superiores de Monterrey. The program was created to optimize the complex clinical and psychosocial care of these patients, enhance education regarding their special needs, and promote targeted research, as well as to replicate this program model in other healthcare centers across Mexico and Latin America. From November 2013 to February 2017, the implementation of the "Joven & Fuerte" program has delivered specialized care to 265patients, through the systematic identification of their particular needs and the provision of fertility, genetic, and psychological supportive services. Patients and families have engaged in pedagogic activities and workshops and have created a motivated and empowered community. The program developed and adapted the first educational resources in Spanish dedicated for young Mexican patients, as well as material for healthcare providers. As for research, a prospective cohort of young breast cancer patients was established to characterize clinicopathological features and psychosocial effects at baseline and during follow-up, as a guide for the development of specific cultural interventions addressing this vulnerable group. Eventually, it is intended that the program's organization and structure can reach national and international interactions and serve as a platform for other countries.

Quality of life of young patients with recurrent respiratory papillomatosis.

To assess quality of life of children and teenagers with recurrent respiratory papillomatosis, according to the evidence of infection by human papillomavirus types 6 and 11, compared with healthy volunteers and patients with chronic otitis media. Participants and their parents completed the Pediatric Quality of Life Inventory 4.0. Patients with recurrent respiratory papillomatosis and their parents reported lower quality of life than healthy subjects (p < 0.01), but similar quality of life to patients with chronic otitis media. Those with human papillomavirus type 11 showed the lowest scores among all participants (p < 0.05). Young Mexican patients with recurrent respiratory papillomatosis and their parents perceive a poor quality of life, and they may experience limitations in interactions with their peers. Infection by human papillomavirus type 11 may increase the impact of the disease on quality of life.

Molecular Subtypes and Prognosis in Young Mexican Women With Breast Cancer

IntroductionYoung age represents an adverse prognostic factor in breast cancer (BC), and young women present with more advanced and aggressive disease. In Latin America, BC is increasing in young women, and there is a lack of information regarding the characteristics and outcomes of this patient population. Patients and MethodsWe retrospectively analyzed a database of 4315 women treated for BC at a single institution. We compared clinical characteristics, treatment, and survival between women ≤ 40 and > 40 years of age. Survival analyses were performed for each molecular subtype. ResultsA total of 662 women (15.3%) were ≤ 40 years old. Younger women had more advanced disease, higher grade, and a larger proportion of luminal B and triple-negative tumors (P < .001). At 5 years, both disease-free and overall survival (OS) were lower in younger women, although there were no differences after adjusting for stage. Five-year OS was worse for young women with hormone receptor-positive, human epidermal growth factor receptor 2-negative subtype (82% vs. 87.1%; P = .03), but not for those with human epidermal growth factor receptor 2-positive or triple-negative disease. This difference can be attributed to luminal B tumors, which showed a worse 5-year OS in younger women (79.1% vs. 85.2%; P = .03). ConclusionAlthough young Mexican patients with BC have more aggressive disease at presentation than older women, only those with luminal B tumors have a worse survival after adjusting for stage. Strategies aimed at downstaging the disease and at improving the treatment of luminal B tumors in this population are needed.

Approximation to the craniofacial pattern by age in a radiographic series of young Mexican patients

Introduction: Facial morphology experiences gradual change by region. Its components and variations are an area of interest in pediatrics, odontology and forensic anthropology among others. Objective:To identify the growth pattern by age and gender from 10 to20 years of age. Material and methods: The study included 450 lateral cephalograms (215 males and 235 females) collected at the Latin American University between 2000 and 2010. Results: The report describes skeletal and soft tissue indicators for growth by age and gender in individuals with ages between 10 and 20 years for each one of the facial thirds. Conclusion: Facial spiral model demonstrates differential patterns for each facial third with a constant separation beginning at age 13.

AIP mutations in young patients with acromegaly and the Tampico Giant: the Mexican experience.

Although aryl hydrocarbon receptor-interacting protein (AIP) mutations are rare in sporadic acromegaly, their prevalence among young patients is nonnegligible. The objectives of this study were to evaluate the frequency of AIP mutations in a cohort of Mexican patients with acromegaly with disease onset before the age of 30 and to search for molecular abnormalities in the AIP gene in teeth obtained from the "Tampico Giant". Peripheral blood DNA from 71 patients with acromegaly (51 females) with disease onset <30years was analysed (median age of disease onset of 23years) and correlated with clinical, biochemical and imaging characteristics. Sequencing was also carried out in DNA extracted from teeth of the Tampico Giant. Five patients (7%) harboured heterozygous, germline mutations of the AIP gene. In two of them (a 9-year-old girl with gigantism and a young man with symptoms of GH excess since age 14) the c.910C>T (p.Arg304Ter), well-known truncating mutation was identified; in one of these two cases and her identical twin sister, the mutation proved to be a de novo event, since neither of their parents were found to be carriers. In the remaining three patients, new mutations were identified: a frameshift mutation (c.976_977insC, p.Gly326AfsTer), an in-frame deletion (c.872_877del, p.Val291_Leu292del) and a nonsense mutation (c.868A>T, p.Lys290Ter), which are predicted to be pathogenic based on in silico analysis. Patients with AIP mutations tended to have an earlier onset of acromegaly and harboured larger and more invasive tumours. A previously described genetic variant of unknown significance (c.869C>T, p.Ala299Val) was identified in DNA from the Tampico Giant. The prevalence of AIP mutations in young Mexican patients with acromegaly is similar to that of European cohorts. Our results support the need for genetic evaluation of patients with early onset acromegaly.

Defective mismatch repair proteins and microsatellite instability in young Mexican patients with colorectal cancer.

e14708 Background: Colorectal carcinoma (CRC) is prevalent malignancy and a third of the cases affect young patients. 15% of CRC have microsatellite instability (MSI) due to disruptions in mismatch repair (MMR) genes, like germline mutations (3%) and hypermethylation of the MLH1 gene promoter associated to the BRAF V600E mutation (12%). The aim of this work was to assess MMR abnormalities in tumors of Mexican CRC patients under 50 years old. Methods: CRC paraffin-embedded tissues of 47 patients with available demographic/clinical data were studied by immunohistochemistry (IHC) for MLH1/MSH2, qPCR with specific probes/sequencing for the BRAF V600E mutation, and conventional PCR (5 markers) for MSI analysis. Results: Female:Male ratio was 0.81:1. Most of the cases were classified as TNM Stage II, were located in the cecum, invaded the serous coat, and showed intestinal-type histology. 20 samples showed alterations in MMR protein expression. MLH1, MSH2, and combined deficiency of both proteins were detected in 17, 4, and 4 tumors, respectively. No BRAF mutations were detected. MSI analysis restricted to the 20 altered IHC samples showed MSI in 10 tumors (3 MSI-low and 7 MSI-high tumors). The four cases with MLH1/MSH2 deficiency, showed MSI-high pattern. Conclusions: We found 42.6% cases with defective MMR expression. No epigenetic abnormalities associated to BRAF V600E mutation were registered. The lack of MSI in ten tumors with deficient MMR may be due to alternate DNA repair mechanisms. Acknowledgments. Work supported by the CHIBCHA Project (European Commission7FP grant #223678).