Population and breast cancer patients' analysis reveals the diversity of genomic variation of the BRCA genes in the Mexican population.

Interpretation of variants of unknown significance (VUS) in genetic tests is complicated in ethnically diverse populations, given the lack of information regarding the common spectrum of genetic variation in clinically relevant genes. Public availability of data obtained from high-throughput genotyping and/or exome massive parallel sequencing (MPS)-based projects from several thousands of outbred samples might become useful tools to evaluate the pathogenicity of a VUS, based on its frequency in different populations. In the case of the Mexican and other Latino populations, several thousands of samples have been genotyped or sequenced during the last few years as part of different efforts to identify common variants associated to common diseases. In this report, we analyzed Mexican population data from a sample of 3985 outbred individuals, and additional 66 hereditary breast cancer patients were analyzed in order to better define the spectrum of common genomic variation of the BRCA1 and BRCA2 genes. Our analyses identified the most common genetic variants in these clinically relevant genes as well as the presence and frequency of specific pathogenic mutations present in the Mexican population. Analysis of the 3985 population samples by MPS identified three pathogenic mutations in BRCA1, only one population sample showed a BRCA1 exon 16-17 deletion by MLPA. This resulted in a basal prevalence of deleterious mutations of 0.10% (1:996) for BRCA1 and 11 pathogenic mutations in BRCA2, resulting in a basal prevalence of deleterious mutations of 0.276% (1:362) for BRCA2, combined of 0.376% (1:265). Separate analysis of the breast cancer patients identified the presence of pathogenic mutations in 18% (12 pathogenic mutations in 66 patients) of the samples by MPS and 13 additional alterations by MLPA. These results will support a better interpretation of clinical studies focused on the detection of BRCA mutations in Mexican and Latino populations and will help to define the general prevalence of deleterious mutations within these populations.

[Breast Cancer Survival: Clinical andPathological Prognostic Factors Analysis]. / Supervivencia de pacientes con cáncer de mama. Análisis por factores pronóstico, clínicos y patológicos.

Background: Breast cancer is the leading cause of cancer death in women in Mexico, is a heterogeneous disease, and knowledge of prognostic factors are critical in making treatment decisions. Objetive: determine the overall survival (OS) and disease-free survival (DFS) at 5 years, analyzed by risk groups. Material and methods: Patients diagnosed with breast treated at the Institute of Breast Diseases FUCAM from July 2005 to December 2014 were included. Simple frequencies were used for analysis of the general characteristics, and 5- year OS and DFS were analyzed using Kaplan-Meier curves. A subset analysis of the clinical stage and comparing survival in those patients diagnosed by mammography screening program was performed. Results: 4,902 patients with breast cancer were included, general clinical and pathological features are described and 3,762 patients were included for analysis of 5-year OS and DFS. The average age at diagnosis was 53.7 years; 13.3% were <40 years, which deleteriously reflects on the supervivencia global 76 vs 84% in >40. At diagnosis predominated locally advanced stages (45%), OS and DFS at 5 years was 96.8 ± 0.6% and 93.4%±0.9 respectively for early stages, 74.6 ± 1.7% and 68.7 ± 2% for locally advanced and 35.9 ± 5.1% and 37.4 ± 10.3% for metastatic tumors. Women diagnosed in the screening program had significantly better OS and DFS compared with symptomatic patients (95 and 93% vs 79 and 77%). For biological subtypes, OS and DFS was 89 and 84% for luminal, 81 and 81% for luminal Her +, 74 and 78% for pure Her 2, and 69 and 73% for triple negative. Conclusion: Knowledge of the prognostic factors that affect survival of patients with breast cancer is essential for categorizing risk groups and to individualize treatment in order to improve life expectancy.

[Use of a questionnaire for screening people with undiagnosed diabetes]. / Utilidad de un cuestionario en la detección de individuos con riesgo de diabetes mellitus asintomática.

OBJECTIVE: To evaluate a screening questionnaire to identify individuals with undiagnosed diabetes. DESIGN AND METHODS: We conducted a community survey to detect people at increased risk for diabetes using a questionnaire proposed by Herman et al. (1995), that incorporates major risk factors as age, obesity, family history of diabetes, sedentary lifestyle and personal history of delivering a macrosomic infant. Blood glucose test was made by means of reagent strip and a reflectance meter system. We used the ADA recommendations and cut-points for screening programs, adjusted for fasting and random blood glucose. RESULTS: We included 360 participants older than 20 years of age. A total of 200 subjects (55.5%) were at risk for diabetes according to the questionnaire, of whom 31 (15.5%) had an abnormal glucose test compared to the 4.4% of the low-risk group (p < 0.001). The 1995 Herman et al. Questionnaire had sensitivity of 81.6%, specificity of 47.5, positive predictive value of 15.5 and negative predictive value of 95.6%. The high-risk group was older (44.9 vs. 34.6 y, p < 0.001) and heavier (30.5 vs. 24.4 kg/m2, p < 0.001) than the low-risk group. There were 38/360 (10.5%) abnormal glucose readings, of which 31 (81.5%) had a positive questionnaire (p < 0.01). The mean fasting glucose in the high-risk group was higher (90.6 vs. 84.2 mg/dL, p = 0.015) than in those with low risk by questionnaire, as well as for random blood glucose (116.1 vs. 100 mg/dL, p < 0.01). CONCLUSIONS: The questionnaire proposed by Herman et al. combined with capillary blood glucose testing performance good in mexican population to identify people at high risk for undiagnosed diabetes, and improved the detection rate.