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GWAS have enhanced our understanding for the genetic basis of breast cancer, but the majority of them were performed for European ancestry populations. Here, the authors use a cross-ancestry approach and report seven new variants associated with breast cancer risk among women of African ancestry.

Abstract Background Breast cancer is a partially heritable trait and genome-wide association studies (GWAS) have identified over 180 common genetic variants associated with breast cancer. We have previously performed breast cancer GWAS in Latinas and identified a strongly protective single nucleotide polymorphism (SNP) at 6q25, with the protective minor allele originating from indigenous American ancestry. Here we report on fine mapping of the 6q25 locus in an expanded sample of Latinas. Methods We performed GWAS in 2385 cases and 6416 controls who were either US Latinas or Mexican women. We replicated the top SNPs in 2412 cases and 1620 controls of US Latina, Mexican, and Colombian women. In addition, we validated the top novel variants in studies of African, Asian and European ancestry. In each dataset we used logistic regression models to test the association between SNPs and breast cancer risk and corrected for genetic ancestry using either principal components or genetic ancestry inferred from ancestry informative markers using a model-based approach. Results We identified a novel set of SNPs at the 6q25 locus associated with genome-wide levels of significance (p = 3.3 × 10− 8 - 6.0 × 10− 9) not in linkage disequilibrium (LD) with variants previously reported at this locus. These SNPs were in high LD (r 2 > 0.9) with each other, with the top SNP, rs3778609, associated with breast cancer with an odds ratio (OR) and 95% confidence interval (95% CI) of 0.76 (0.70–0.84). In a replication in women of Latin American origin, we also observed a consistent effect (OR 0.88; 95% CI 0.78–0.99; p = 0.037). We also performed a meta-analysis of these SNPs in East Asians, African ancestry and European ancestry populations and also observed a consistent effect (rs3778609, OR 0.95; 95% CI 0.91–0.97; p = 0.0017). Conclusion Our study adds to evidence about the importance of the 6q25 locus for breast cancer susceptibility. Our finding also highlights the utility of performing additional searches for genetic variants for breast cancer in non-European populations.

Low circulating levels of vitamin D and high mammographic density (MD) have been associated with higher risk of breast cancer. Although some evidence suggested an inverse association between circulating vitamin D and MD, no studies have investigated this association among Mexican women. We examined whether serum 25-hydroxyvitamin D3 [25(OH)D3] levels were associated with MD in a cross-sectional study nested within the large Mexican Teacher's Cohort. This study included 491 premenopausal women with a mean age of 42.9 years. Serum 25(OH)D3 levels were measured by liquid chromatography/tandem mass spectrometry. Linear regression and non-linear adjusted models were used to estimate the association of MD with serum 25(OH)D3. Median serum 25(OH)D3 level was 27.3 (23.3-32.8) (ng/ml). Forty one (8%) women had 25(OH)D3 levels in the deficient range (< 20 ng/ml). Body mass index (BMI) and total physical activity were significantly correlated with 25(OH)D3 (r = -0.109, P = 0.019 and r = 0.095, P = 0.003, respectively). In the multivariable linear regression, no significant association was observed between 25(OH)D3 levels and MD overall. However, in stratified analyses, higher serum 25(OH)D3 levels (≥27.3 ng/ml) were significantly inversely associated with percent MD among women with BMI below the median (β = -0.52, P = 0.047). Although no significant association was observed between serum 25(OH)D3 and percent MD in the overall population, specific subgroups of women may benefit from higher serum 25(OH)D3 levels.

Selenoproteins are a class of proteins containing a selenocysteine residue, many of which have been shown to have redox functions, acting as antioxidants to decrease oxidative stress. Selenoproteins have previously been associated with risk of various cancers and redox-related diseases. In this study we evaluated possible associations between breast cancer risk and survival and single nucleotide polymorphisms (SNPs) in the selenoprotein genes GPX1, GPX2, GPX3, GPX4, SELS, SEP15, SEPN1, SEPP1, SEPW1, TXNRD1, and TXNRD2 among Hispanic/Native American (2111 cases, 2597 controls) and non-Hispanic white (NHW) (1481 cases, 1586 controls) women in the Breast Cancer Health Disparities Study. Adaptive Rank Truncated Product (ARTP) analysis was used to determine both gene and pathway significance with these genes. The overall selenoprotein pathway PARTP was not significantly associated with breast cancer risk (PARTP = 0.69), and only one gene, GPX3, was of borderline significance for the overall population (PARTP =0.09) and marginally significant among women with 0-28% Native American (NA) ancestry (PARTP=0.06). The SEPP1 gene was statistically significantly associated with breast cancer risk among women with higher NA ancestry (PARTP=0.002) and contributed to a significant pathway among those women (PARTP=0.04). GPX1, GPX3, and SELS were associated with Estrogen Receptor-/Progesterone Receptor+ status (PARTP = 0.002, 0.05, and 0.01, respectively). Four SNPs (GPX3 rs2070593, rsGPX4 rs2074451, SELS rs9874, and TXNRD1 rs17202060) significantly interacted with dietary oxidative balance score after adjustment for multiple comparisons to alter breast cancer risk. GPX4 was significantly associated with breast cancer survival among those with the highest NA ancestry (PARTP = 0.05) only. Our data suggest that SEPP1 alters breast cancer risk among women with higher levels of NA ancestry.

Matrix metalloproteinases (MMPs) contribute to cancer through their involvement in cancer invasion and metastasis. We evaluated genetic variation in MMP1 (9 SNPs), MMP2 (8 SNPs), MMP3 (4 SNPs), and MMP9 (3 SNPs) and breast cancer risk among Hispanic (2111 cases, 2597 controls) and non-Hispanic white (NHW) (1481 cases, 1586 controls) women in the Breast Cancer Health Disparities Study. Ancestral informative markers (n = 104) were assessed to determine Native American (NA) ancestry. MMP1 [4 single nucleotide polymorphisms (SNPs)] and MMP2 (2 SNPs) were associated with breast cancer overall. MMP1 rs996999 had strongest associations among women with the most NA ancestry (OR 1.61,95% CI 1.09,2.40) as did MMP3 rs650108 (OR 1.36, 95% CI 1.05,1.75) and MMP9 rs3787268 (OR 1.52, 95% CI 1.09,2.13). The adaptive rank truncated product (ARTP) showed a significant pathway p(artp) value of 0.04, with a stronger association among women with the most NA ancestry (p(artp) = 0.02). Significant pathway genes using the ARTP were MMP1 for all women (p(artp) = 0.02) and MMP9 for women with the most NA ancestry (p(artp) = 0.024); MMP2 was borderline significant overall (p(artp) =0.06) and MMP1 and MMP3 were borderline significant for women with the most NA ancestry (p(artp) = 0.07 and 0.06 respectively). MMP1 and MMP2 were associated with ER+/PR+ and ER+/PR-tumors; MMP3 and MMP9 were associated with ER-/PR- tumors. The pathway was highly significant with survival (p(artp) = 0.0041) with MMP2 having the strongest gene association (p(artp) = 0.0007). Our findings suggest that genetic variation in MMP genes influence breast cancer development and survival in this genetically admixed population.

Abstract Less than 15–20% of patients who meet the criteria for hereditary breast and ovarian cancer (HBOC) carry pathogenic coding genetic mutations, implying that other molecular mechanisms may contribute to the increased risk of this condition. DNA methylation in peripheral blood has been suggested as a potential epigenetic marker for the risk of breast cancer (BC). We aimed to discover methylation marks in peripheral blood associated with BC in 231 pre-treatment BC patients meeting HBOC criteria, testing negative for coding pathogenic variants, and 156 healthy controls, through methylation analysis by targeted bisulfite sequencing on 18 tumor suppressor gene promoters (330 CpG sites). We found i) hypermethylation in EPCAM (17 CpG sites; p = 0.017) and RAD51C (27 CpG sites; p = 0.048); ii) hypermethylation in 36 CpG-specific sites (FDR q

Abstract Background Latin American and Hispanic women are less likely to develop breast cancer (BC) than women of European descent. Observational studies have found an inverse relationship between the individual proportion of Native American ancestry and BC risk. Here, we use ancestry-informative markers to rule out potential confounding of this relationship, estimating the confounder-free effect of Native American ancestry on BC risk. Methods and study population We used the informativeness for assignment measure to select robust instrumental variables for the individual proportion of Native American ancestry. We then conducted separate Mendelian randomization (MR) analyses based on 1401 Colombian women, most of them from the central Andean regions of Cundinamarca and Huila, and 1366 Mexican women from Mexico City, Monterrey and Veracruz, supplemented by sensitivity and stratified analyses. Results The proportion of Colombian Native American ancestry showed a putatively causal protective effect on BC risk (inverse variance-weighted odds ratio [OR] = 0.974 per 1% increase in ancestry proportion, 95% confidence interval [CI] 0.970–0.978, p = 3.1 × 10–40). The corresponding OR for Mexican Native American ancestry was 0.988 (95% CI 0.987–0.990, p = 1.4 × 10–44). Stratified analyses revealed a stronger association between Native American ancestry and familial BC (Colombian women: OR = 0.958, 95% CI 0.952–0.964; Mexican women: OR = 0.973, 95% CI 0.969–0.978), and stronger protective effects on oestrogen receptor (ER)-positive BC than on ER-negative and triple-negative BC. Conclusions The present results point to an unconfounded protective effect of Native American ancestry on BC risk in both Colombian and Mexican women which appears to be stronger for familial and ER-positive BC. These findings provide a rationale for personalised prevention programmes that take genetic ancestry into account, as well as for future admixture mapping studies.

Abstract Background Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes. Methods We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes’ coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry. Results In European ancestry samples, 14 genes were significantly associated (q

Abstract Background Breast cancer incidence is increasing rapidly in Latin America, with a higher proportion of cases among young women than in developed countries. Studies have linked inflammation to breast cancer development, but data is limited in premenopausal women, especially in Latin America. Methods We investigated the associations between serum biomarkers of chronic inflammation (interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), leptin, adiponectin) and risk of premenopausal breast cancer among 453 cases and 453 matched, population-based controls from Chile, Colombia, Costa Rica, and Mexico. Odds ratios (OR) were estimated using conditional logistic regression models. Analyses were stratified by size and hormonal receptor status of the tumors. Results IL-6 (ORper standard deviation (SD) = 1.33 (1.11–1.60)) and TNF-α (ORper SD = 1.32 (1.11–1.58)) were positively associated with breast cancer risk in fully adjusted models. Evidence of heterogeneity by estrogen receptor (ER) status was observed for IL-8 (P-homogeneity = 0.05), with a positive association in ER-negative tumors only. IL-8 (P-homogeneity = 0.06) and TNF-α (P-homogeneity = 0.003) were positively associated with risk in the largest tumors, while for leptin (P-homogeneity = 0.003) a positive association was observed for the smallest tumors only. Conclusions The results of this study support the implication of chronic inflammation in breast cancer risk in young women in Latin America. Largest studies of prospective design are needed to confirm these findings in premenopausal women.

Abstract Breast cancer is a multifactorial disease in which the interplay among multiple risk factors remains unclear. Energy homeostasis genes play an important role in carcinogenesis and their interactions with the serum concentrations of IGF-1 and IGFBP-3 on the risk of breast cancer have not yet been investigated. The aim of this study was to assess the modifying effect of the genetic variation in some energy homeostasis genes on the association of serum concentrations of IGF-1 and IGFBP-3 with breast cancer risk. We analyzed 78 SNPs from 10 energy homeostasis genes in premenopausal women from the 4-Corner’s Breast Cancer Study (61 cases and 155 controls) and the Mexico Breast Cancer Study (204 cases and 282 controls). After data harmonization, 71 SNPs in HWE were included for interaction analysis. Two SNPs in two genes (MBOAT rs13272159 and NPY rs16131) showed an effect modification on the association between IGF-1 serum concentration and breast cancer risk (P interaction

Objective. To assess whether the Catastrophic Health Expenditures Fund (FPGC, Spanish acronym) was associated with delays in seeking medical care and in starting treatment. Materials and methods. We conducted a before and after cross-sectional study. We included 266 women with breast cancer (BC) diagnosis treated during the last three years before the hospitals received the FPGC and 309 wo­men treated in the following three years after the fund was received by the accredited hospitals. Results. After adjusting for potential confounders, we found no association between the FPGC and delay in seeking medical care or between the FPGC and the treatment delay. Conclusions. The FPGC initiative reduced neither the delay in seeking breast cancer medical care for breast cancer nor the treatment delay.

Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite their notable anthropometric variability, ancestry proportions, and high burden of growth stunting and overweight/obesity. To address this knowledge gap, we analyzed densely imputed genetic data in a sample of Hispanic/Latino adults to identify and fine-map genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (stage 1, n = 59,771) and generalized our findings in 9 additional studies (stage 2, n = 10,538). We conducted a trans-ancestral GWAS with summary statistics from HISLA stage 1 and existing consortia of European and African ancestries. In our HISLA stage 1 + 2 analyses, we discovered one BMI locus, as well as two BMI signals and another height signal each within established anthropometric loci. In our trans-ancestral meta-analysis, we discovered three BMI loci, one height locus, and one WHRadjBMI locus. We also identified 3 secondary signals for BMI, 28 for height, and 2 for WHRadjBMI in established loci. We show that 336 known BMI, 1,177 known height, and 143 known WHRadjBMI (combined) SNPs demonstrated suggestive transferability (nominal significance and effect estimate directional consistency) in Hispanic/Latino adults. Of these, 36 BMI, 124 height, and 11 WHRadjBMI SNPs were significant after trait-specific Bonferroni correction. Trans-ancestral meta-analysis of the three ancestries showed a small-to-moderate impact of uncorrected population stratification on the resulting effect size estimates. Our findings demonstrate that future studies may also benefit from leveraging diverse ancestries and differences in linkage disequilibrium patterns to discover novel loci and additional signals with less residual population stratification.

Objective. To describe the rationale and the method­ology of a multicenter project to study the etiology of breast cancer in young Latin American women. Materials and methods. The International Agency for Research on Cancer has established an international collaborative population-based case-control study in four countries in Latin America: Chile, Colombia, Costa Rica, and Mexico (the PRECAMA study). Standardized methodologies were developed to collect information on reproductive variables, lifestyle, anthropometry, diet, clinical and pathological data, and biological specimens. The study will be extended to other countries in the region. Conclusion. PRECAMA is unique in its multidisciplinary approach that combines genet­ics, genomics, and metabolomics with lifestyle factors. The data generated through this project will be instrumental to identify major risk factors for molecular subtypes of breast cancer in young women, which will be important for pre­vention and targeted screening programs in Latin America.

Abstract Background Thyroxine (T4) has been positively associated with tumor cell proliferation, while the effect of triiodothyronine (T3) on cell proliferation has not been well-established because it differs according to the type of cell line used. In Mexico, it has been reported that 14.5% of adult women have some type of thyroid dysfunction and abnormalities in thyroid function tests have been observed in a variety of non-thyroidal illnesses, including breast cancer (BC). These abnormalities might change with body mass index (BMI) because thyroid hormones are involved in the regulation of various metabolic pathways and probably by menopausal status because obesity has been negatively associated with BC in premenopausal women and has been positively associated with BC in postmenopausal women. Methods To assess the association between serum thyroid hormone concentration (T4 and T3) and BC and the influence of obesity as an effect modifier of this relationship in premenopausal and postmenopausal women, we measured serum thyroid hormone and thyroid antibody levels in 682 patients with incident breast cancer (cases) and 731 controls, who participated in a population-based case-control study performed from 2004 to 2007 in three states of Mexico. We tested the association of total T4 (TT4) and total T3 (TT3) stratifying by menopausal status and body mass index (BMI), and adjusted for other health and demographic risk factors using logistic regressions models. Results Higher serum total T4 (TT4) concentrations were associated with BC in both premenopausal (odds ratio (OR) per standard deviation = 5.98, 95% CI 3.01–11.90) and postmenopausal women (OR per standard deviation = 2.81, 95% CI 2.17–3.65). In premenopausal women, the effect of TT4 decreased as BMI increased while the opposite was observed in postmenopausal women. The significance of the effect modification was marginal (p = 0.059) in postmenopausal women and was not significant in premenopausal women (p = 0.22). Lower TT3 concentrations were associated with BC in both premenopausal and postmenopausal women and no effect modification was observed. Conclusions There is a strong association between BC and serum concentrations of TT3 and TT4; this needs to be further investigated to understand why it happens and how important it is to consider these alterations in treatment.

Fatty acids (FAs) have been postulated to impact adiposity, but few epidemiological studies addressing this hypothesis have been conducted. This study investigated the association between serum phospholipid FAs (S-PLFAs) and indicators of obesity. BMI and waist-to-hip ratio (WHR) were collected from 372 healthy Mexican women included as controls in a case-control study. S-PLFA percentages were determined through gas chromatography. Desaturation indices, SCD-16, SCD-18, FA desaturase (FADS)1, and FADS2, biomarkers of endogenous metabolism, were proxied respectively as 16:1n-7/16:0, 18:1n-9/18:0, 20:4n-6/20:3n-6, and 22:6n-3/20:5n-3. Multiple linear regressions adjusted for relevant confounders and corrected for multiple testing were conducted to determine the association between S-PLFA, desaturation indices, and indicators of adiposity. SCD-16 (β = 0.034, P = 0.001, q = 0.014), palmitoleic acid (β = 0.031, P = 0.001, q = 0.014), and dihomo-γ-linolenic acid (β = 0.043, P = 0.000, q = 0.0002) were positively associated with BMI. Total n-6 PUFAs (β = 1.497, P = 0.047, q = 0.22) and the ratio of n-6/n-3 PUFAs (β = 0.034, P = 0.040, q = 0.19) were positively associated with WHR, while odd-chain FAs (pentadecanoic and heptadecanoic acid) showed negative associations with all the adiposity indicators. In conclusion, increased endogenous synthesis of palmitoleic acid and a high n-6/n-3 ratio are associated with increased adiposity, while odd-chain FAs are associated with decreased adiposity. Further studies are needed to determine the potential causality behind these associations.

AimTo assess the adherence of physicians to the Medical-Care Guidelines for Malignant Breast Tumors in Mexico, before and after the allocation of federal subsidies from the Catastrophic Health Expenditure Fund (FPGC by its Spanish initials) to accredited hospitals, a strategy implemented with the view of offering free treatment to women with breast cancer (BC).Material and methodsBased on a cross-sectional design, we gathered information on 479 BC patients who had been attended to at in four FPGC-accredited hospitals. Analysis centered on those treated within either three years before or three years after the accreditation of their attending hospitals. The four hospitals analyzed were located in the North, South, West and Center of the country. Information on all medical procedures performed during treatment was drawn from hospital medical records. Information on the socio-demographic characteristics of the patients was obtained by means of face-to-face interviews conducted in their homes.ResultsAdherence of physicians to the Guidelines grew by 12.8 percent (from 43.4 to 56.2 percent) after FPGC accreditation (pConclusionsThe FPGC strategy increased the adherence of physicians to the Medical-Care Guidelines for Malignant Breast Tumors in Mexico.

BackgroundIn Latin America (LA), there is a high incidence rate of breast cancer (BC) in premenopausal women, and the genomic features of these BC remain unknown. Here, we aim to characterize the molecular features of BC in young LA women within the framework of the PRECAMA study, a multicenter population-based case-control study of BC in premenopausal women.MethodsPathological tumor tissues were collected from incident cases from four LA countries. Immunohistochemistry (IHC) was performed centrally for ER, PR, HER2, Ki67, EGFR, CK5/6, and p53 protein markers. Targeted deep sequencing was done on genomic DNA extracted from formalin-fixed, paraffin-embedded tumor tissues and their paired blood samples to screen for somatic mutations in eight genes frequently mutated in BC. A subset of samples was analyzed by exome sequencing to identify somatic mutational signatures.ResultsThe majority of cases were positive for ER or PR (168/233; 72%), and 21% were triple-negative (TN), mainly of basal type. Most tumors were positive for Ki67 (189/233; 81%). In 126 sequenced cases, TP53 and PIK3CA were the most frequently mutated genes (32.5% and 21.4%, respectively), followed by AKT1 (9.5%). TP53 mutations were more frequent in HER2-enriched and TN IHC subtypes, whereas PIK3CA/AKT1 mutations were more frequent in ER-positive tumors, as expected. Interestingly, a higher proportion of G:C>T:A mutations was observed in TP53 in PRECAMA cases compared with TCGA and METABRIC BC series (27% vs 14%). Exome-wide mutational patterns in 10 TN cases revealed alterations in signal transduction pathways and major contributions of mutational signatures caused by altered DNA repair pathways.ConclusionsThese pilot results on PRECAMA tumors give a preview of the molecular features of premenopausal BC in LA. Although the overall mutation burden was as expected from data in other populations, mutational patterns observed in TP53 and exome-wide suggested possible differences in mutagenic processes giving rise to these tumors compared with other populations. Further -omics analyses of a larger number of cases in the near future will enable the investigation of relationships between these molecular features and risk factors.

Objective. To compare trends in hospital discharges and mortality due to breast cancer (BC) in Mexico from 2004 to 2012 by insurance condition before and after incorporating BC comprehensive treatment into the System of Social Protection in Health (Sistema de Protrección Social en Salud, SPSS) in 2007. Materials and methods. Data on BC hospital discharges and mortality reported in women aged 25 years and over were obtained from the National Health Information System. Mortality rates were adjusted by age and state. Results. At the national level, a growing tendency in hospital discharges was observed, mainly for women without social security, while mortality rate remained constant. Mortality rates by state show that lower marginalization index corresponded to higher mortality. Conclusions. A differential behavior was observed among women according to insurance condition, partly due to the inclusion of BC treatment in the SPSS. DOI: http://dx.doi.org/10.21149/spm.v58i2.7788

Objective. To estimate the effect of care-delivery delays on survival among women with breast cancer. Materials and methods. A retrospective analysis of 854 women attending 11 hospitals from 2007-2009 was carried out. Kaplan-Meier estimators and a Cox proportional-risk model were employed. Results. A total of 10.5% of cases were diagnosed in stage I. 82% of sampled women delayed care for more than 67 days between noticing a symptom and initiating treatment. The median time from receipt of results of the mammography to biopsy was 31 days (IQR 14-56). Compared with those who were in quartile I (Q1), survival was lower among those in Q3 and Q4 (HR=1.68, 95%CI 0.94-3.00; HR=1.76, 95% CI 1.04-2.98, respectively). Conclusions. To increase survival, it is suggested that the time between receipt of the mammo- graphy results and diagnostic biopsy be reduced. DOI: http://dx.doi.org/10.21149/spm.v58i2.7793

To identify, measure and compare the performance indicators of productivity, effective access and quality service for the early detection breast cancer program in Mexico. Material and methods. By means of a study case based on the 2011 Women Cancer Information System (Sicam), the indicators were measured and compared with the Mexican official standard NOM-041-SSA2-2011 and international standards. Results. The analysis showed insufficient installed capacity (37%), low coverage in screening (15%), diagnostic evaluation (16%), biopsy (44%) and treatment (57%), and very low effectiveness in confirmed cases by the total number of screening mammograms performed (0.04%). There was no information available, from Sicam, to estimate the rest of the indicators proposed. Conclusions. Efficient health information systems are required in order to monitor indicators and generate performance observatories of screening programs.

Breast cancer is a major public health problem in Latin America (LA) and the most common form of cancer among women. An important variability according to ethnicity/race with respect to incidence/mortality, clinical characteristics, and prognosis is observed throughout LA. In addition, women are more likely to develop breast cancer (BC) at younger age and to be diagnosed at an advanced stage compared to western women. While little is known about specific risk factors, changes in reproductive pattern (parity, breastfeeding) and lifestyle factors including sedentary behaviours, unhealthy diet, and alcohol intake may contribute to the increase of BC incidence. In this paper we give an overview of the burden and patterns of BC, review the leading causes of BC and discuss the possible ways to improve BC prevention and control in LA.

This cross-sectional study aimed to evaluate associations between a priori defined dietary patterns and anthropometric measures in Mexican women. A total of 1062 women aged 35 to 69 years old from the control participants of the CAMA (Cancer de Mama) study, a multi-center population-based case-control study on breast cancer conducted in Mexico, were interviewed and dietary intakes were assessed using questionnaires. The following indices were derived from these data: Dietary Approaches to Stop Hypertension (DASH) score, the Healthy Eating Index (HEI), the Mediterranean Diet Score (aMED), the Diet Quality Index (DQI), glycemic index (GI) and glycemic load (GL). Adjusting for age, center, educational level, physical activity and energy intake, a high GI was positively associated with a higher body mass index (BMI) and waist circumference (WC). Higher adherence to aMED was associated with lower WC and waist-to-hip ratio (WHR) but no significant association was observed with other a priori dietary patterns. In this population of Mexican women, higher adherence to Mediterranean diet was associated with lower WC but other a priori dietary scores appeared to be of limited value in exploring the association between diet and anthropometric measures.

El cáncer de mama ha trascendido como un importante riesgo para la salud de las mujeres a escala mundial. Las muertes por cáncer de mama han tenido un destacado incremento dentro de los tumores malignos a nivel mundial al cobrar más de 460 000 vidas en 2008, convirtiéndolo en el padecimiento con más decesos alrededor del mundo.Los cambios demográficos y en estilos de vida han modificado la exposición de la población al riesgo de enfermedades como el cáncer,y desde 1980la mortalidad porcáncerdemama ha mantenido una tendencia ascendente,ubicándose por encima de las muertes por cáncer cervicouterino desde 2006. Al analizar las tasas de mortalidad en las mujeres mexicanas de 25 años de edad en adelante a lo largo de 30 años, se distinguen diferencias estatales y por grupos de edad. Aun cuando el perfil de esta causa de muerte se ha asociado con un mayor desarrollo regional, en este trabajo se puede observar que están ocurriendo cambios y las muertes también están creciendo en la población de mujeres de regiones y entidades menos desarrolladas.Queda de manifiesto el reto que México enfrenta, y la necesidad de conjuntar esfuerzos e implementar programas para educar a la población hacia el autocuidado de la salud, así como promover estilos de vida saludables, además de mejorar la infraestructura diagnóstica para lograr una detección a tiempo y garantizar un tratamiento adecuado.Breast cancer has become an important health risk for women worldwide.The important growth of breast cancer-related deaths within those caused by malign tumors throughout the globe went past the 460 000 in 2008,becoming the deadliest disease worldwide.Demographic changes and lifestyles have modified the population exposure to risk factors of maladies such as cancer, and since 1980 breast cancer mortality has remained on an upward tendency,surpassing cervical cancer in 2006. After analyzing mortality rates along 30 years in Mexican women 25 or more years old, differences by state and age-groups are apparent. Although this cause of death has been associated with a highest regional development, some changes are taking place,since the number of deaths is also growing among women of less-developed regions in the country,as showed in this work.Mexico faces an evident challenge regarding breast cancer. Our country requires to join efforts and implement programs aimed at teaching self-care of health among the population,promoting healthier lifestyles, and reshaping our diagnostic infrastructure to achieve earlier detection and provide proper treatment.

OBJETIVO: Evaluar los factores pronósticos del cáncer de mama en mujeres mexicanas. MATERIAL Y MÉTODOS: Se incluyó a 432 mujeres con cáncer de mama admitidas de 1990 a 1999 en el Hospital General de México para evaluar la supervivencia mediante las técnicas de Kaplan-Meier y los métodos de riesgos proporcionales de Cox. RESULTADOS: La supervivencia global a cinco años fue de 58.9%. La menor supervivencia corresponde a los estadios clínicos IIIB (47.5%), IIIA (44.2%) y IV(15%), la metástasis hematógena fue de 21.4% y el tumor positivo en bordes quirúrgicos de 12.5%. La invasión linfovascular (RR= 1.9; IC95% 1.3-2.8), el estadio clínico IV (RR= 14.8; IC95% 5.5-39.7) y el tumor en bordes quirúrgicos (RR= 2.4; IC95% 1.2-4.8) fueron los principales factores pronósticos. CONCLUSIONES: Estos resultados dan consistencia a los criterios de diagnóstico y tratamiento de las mujeres con cáncer de mama atendidas en México y toman en consideración las condiciones de la tumoración, como extensión de la malformación, etapa clínica y estado de los ganglios linfáticos antes de decidir la conducta terapéutica inicial.OBJECTIVE: To evaluate prognostic factors for breast cancer in Mexican women. MATERIAL AND METHODS: Four hundred and thirty two women with breast cancer, admitted from 1990 to 1999 to the General Hospital of Mexico, were included to evaluate their survival using the Kaplan-Meier technique and Cox proportional hazard method. RESULTS: Overall 5-year survival was 58.9%. The shortest survival rate corresponds to the clinical stage (IIIB, 47.5%; IIIA, 44.2%; and IV, 15%), the haematological metastasis (21.4%) and surgical edges with positive tumor (12.5%). Lymph node-positive (RR, 1.9; IC95%, 1.3-2.8), clinical stage IV (RR, 14.8; IC95%, 5.5-39.7) and surgical edges with positive tumor (RR, 2.4; IC95%, 1.2-4.8) were the central prognostic factors. CONCLUSIONS: These results give consistency to diagnostic and therapeutic criteria for women with breast cancer who receive medical attention in Mexico, taking into consideration the characteristics of the tumor -such as extension, clinical stage and status of the lymph nodes- before making a decision as to the initial therapy.

OBJETIVO: Evaluar el efecto de la actividad física moderada (en horas por semana y METs-hora por semana) sobre el riesgo de cáncer de mama (CM). MATERIAL Y MÉTODOS: Se trata de la primera fase de un estudio multicéntrico de casos y controles con base poblacional que se desarrolló en el Distrito Federal, Monterrey y Veracruz, México, en el año 2004. Se analizaron 58 casos y 58 controles pareados a los casos por quinquenio de edad, y pertenencia al sistema de salud; participaron tres hospitales del Instituto Mexicano del Seguro Social, tres del Instituto de Seguridad Social al Servicio de los Trabajadores del Estado y tres de la Secretaría de Salud. RESULTADOS: En mujeres posmenopáusicas se observó una reducción del riesgo de CM por cada hora semanal adicional de actividad física moderada (RM= 0.91; IC95% 0.85-0.97); en mujeres premenopáusicas, la disminución del riesgo no tuvo significancia estadística (RM= 0.99; IC95% 0.94-1.05) (p= 0.048, modificación de efecto). CONCLUSIONES: La actividad física reduce el riesgo de CM en mujeres mexicanas posmenopáusicas.OBJECTIVE: To evaluate the effect of moderate physical activity (hours per week and METs hours per week) on the risk of breast cancer (BC) in Mexican women. MATERIAL AND METHODS: This is the initial stage of a case control multicentric study based in the Federal District, Monterrey and Veracruz, Mexico, during 2004. Fifty eight cases paired to 58 control cases on quinquennium of age, and belonging to the health system were analyzed: three hospitals from the IMSS, three from ISSSTE and three from SS participated. RESULTS: In postmenopausal women, there was a reduction of the risk in BC by every additional hour per week of moderate physical activity (RM= 0.91; IC95% 0.85-0.97); in premenopausal women, the reduction of the risk was not statistically significant (RM= 0.99; IC95% 0.94-1.05) (p= 0.048, effect modification). CONCLUSIONS: Moderate physical activity reduces the risk of BC in postmenopausal Mexican women.

The use of hormonal therapies, including hormonal contraceptives (HC) and postmenopausal hormone replacement therapy (HRT) have been shown to influence breast cancer (BC) risk. However, the variations of these effects among populations and ethnic groups are not completely documented, especially among Hispanic women. We evaluated the association between HC and premenopausal BC risk, and between HRT and postmenopausal BC risk in Mexican women. Data from a Mexican multi-center population-based case-control study ofwomen aged 35 to 69 years were analysed. A total of 1000 cases and 1074 matched controls were recruited between 2004 and 2007. Information on hormonal therapy was collected through a structured questionnaire. Results were analysed using conditional logistic regression models. Overall, HC were used by 422/891 (47.3%) premenopausal women and HRT was used by 220/1117 (19.7%) postmenopausal women. For HC, odds ratios (ORs) for BC were 1.11 (95% confidence interval (CI): 0.82, 1.49) for current users and 1.68 (95% CI: 0.67, 4.21) for ever-users. No clear effect of duration of use was observed. For HRT, the OR for BC was significantly increased in ever users (OR: 1.45; 95% CI: 1.01, 2.08). A non-significant increased risk was observed for combined estrogen/progestin, (OR = 1.85; 95% CI: 0.84, 4.07) whereas no effect was observed for the use of estrogen alone (OR = 1.14; 95% CI: 0.68, 1.91). Our results indicate that, HC had a non-significant effect on the risk of pre-menopausal BC, but suggested that injected contraceptives may slightly increase the risk, whereas HRT had a significant effect on post-menopausal BC in this population. This study provides new information about the effects of HC and HRT on BC risk in a Mexican population, which may be of relevance for the population of Latin America as a whole.

The population of Argentina is the result of the intermixing between several groups, including Indigenous American, European and African populations. Despite the commonly held idea that the population of Argentina is of mostly European origin, multiple studies have shown that this process of admixture had an impact in the entire Argentine population. In the present study we characterized the distribution of Indigenous American, European and African ancestry among individuals from different regions of Argentina and evaluated the level of discrepancy between self-reported grandparental origin and genetic ancestry estimates. A set of 99 autosomal ancestry informative markers (AIMs) was genotyped in a sample of 441 Argentine individuals to estimate genetic ancestry. We used non-parametric tests to evaluate statistical significance. The average ancestry for the Argentine sample overall was 65% European (95%CI: 63-68%), 31% Indigenous American (28-33%) and 4% African (3-4%). We observed statistically significant differences in European ancestry across Argentine regions [Buenos Aires province (BA) 76%, 95%CI: 73-79%; Northeast (NEA) 54%, 95%CI: 49-58%; Northwest (NWA) 33%, 95%CI: 21-41%; South 54%, 95%CI: 49-59%; p

OBJETIVO: Generar información de costo-efectividad para optimizar las políticas para el cáncer de mama (CaMa) en México. MATERIAL Y MÉTODOS: Se construyó un modelo Markov que incorpora cuatro procesos interrelacionados del CaMa: la evolución natural, la detección con mamografía, el tratamiento y la dinámica de mortalidad por otras causas, a partir del cual se modelaron 13 estrategias. RESULTADOS: Las estrategias (edad de inicio, porcentaje de cobertura, periodicidad en años)= (48, 25, 2), (40, 50, 2) y (40, 50, 1) representan la ruta óptima de expansión del programa, con un costo por año de vida ganado de 75.3, 116.4 y 171.1 (miles de pesos), respectivamente. CONCLUSIONES: Las estrategias sobre la vía óptima de expansión del programa producen una razón de costo por año de vida ganado menor a dos veces el PIB per cápita, por lo que se encuentran dentro de lo que se considera una intervención costo-efectiva según los criterios de la OMS.OBJECTIVE: Generate cost-effectiveness information to allow policy makers optimize breast cancer (BC) policy in Mexico. MATERIAL AND METHODS: We constructed a Markov model that incorporates four interrelated processes of the disease: the natural history; detection using mammography; treatment; and other competing-causes mortality, according to which 13 different strategies were modeled. RESULTS: Strategies (starting age, % of coverage, frequency in years)= (48, 25, 2), (40, 50, 2) and (40, 50, 1) constituted the optimal method for expanding the BC program, yielding 75.3, 116.4 and 171.1 thousand pesos per life-year saved, respectively. CONCLUSIONS: The strategies included in the optimal method for expanding the program produce a cost per life-year saved of less than two times the GNP per capita and hence are cost-effective according to WHO Commission on Macroeconomics and Health criteria.

La edad temprana de la menarca y tardía de la menopausia, la nuliparidad y la edad tardía de la madre en el primer embarazo se han relacionado con un incremento del riesgo de cáncer de mama (CaMa). Por el contrario, la paridad y el aumento del tiempo en meses de lactancia, en particular la que se ofrece al primer hijo, se han vinculado con un riesgo menor. La hipótesis de que la función ovárica, a través de sus hormonas, desempeña una función importante en el origen del cáncer de mama se ha sustentado en diversos estudios durante mucho tiempo. Aunque la mayor parte de los factores de riesgo relacionados con las características reproductivas es difícil de modificar, incrementar los meses de lactancia y evitar la exposición a los carcinógenos conocidos durante los periodos de desarrollo de la glándula mamaria son medidas para reducir el riesgo de esta enfermedad.Early age at menarche and late age at menopause, nulliparity, and late age at first pregnancy have been associated with an increased risk of BC. In contrast, parity and the increase in time breastfeeding, particularly during the first child have been associated with a decreased risk. The hypothesis that ovarian function, through their hormones, plays an important role in the etiology of breast cancer has been supported by various studies for a long time. Although most of the risk factors associated with reproductive characteristics are difficult to modify, to increase the breastfeeding time and to avoid exposure to known carcinogens during periods of development of the mammary gland are good strategies to reduce the risk of this disease.

OBJECTIVE: To determine the age of peak bone mass (PBM) in Mexican women and factors associated with both BMDa and corrected BMD (BMDcorr) at the femoral neck and the spine (L2-L4). MATERIAL AND METHODS: Data on 461 women between 9 and 24 years old was used. An interview was performed and height and weight were measured. BMDa was measured by a densitometer and BMDcorr by the method proposed by Kröger et al. (1992). RESULTS: PBM at the spine (L2-L4) was observed later than at the femoral neck. Both BMDa and BMDcorr at the lumbar spine correlate with age, socio-economic status, body fat percentage and height. BMDa at the femoral neck correlates with overweight and obesity, body fat percentage, height and moderate physical activity; the same variables were associated with BMDcorr except for height. CONCLUSIONS: The method proposed by Kröger et al. was more precise at the femoral neck than at the spine.OBJETIVO: Determinar la edad del pico de masa ósea (PMO) y los factores asociados a DMOa y a DMOcorr del cuello femoral y de la columna vertebral (L2-L4) en mujeres mexicanas. MATERIAL Y MÉTODOS: Se utilizaron datos de 461 mujeres de 9 a 24 años de edad. La DMO se midió mediante un densitómetro y la DMOcorr mediante el método propuesto por Kröger et al. (1992). RESULTADOS: El PMO en la columna vertebral (L2-L4) se observó más tarde que en el cuello femoral. A la DMOa y DMOcorr de la columna se asociaron: edad, estado socio económico, porcentaje de grasa corporal y la talla. A DMOa del cuello femoral se asociaron: sobrepeso y obesidad, porcentaje de grasa corporal, talla y actividad física moderada; las mismas variables se asociaron con la DMOcorr excepto talla. CONCLUSIONES: El método propuesto por Kröger et al. fue más preciso para el cuello femoral que para la columna.

Multicomponent alloys have attained general interest in recent years due to their remarkable performance. Non-equiatomic alloys with boron addition as an interstitial element are being studied, exhibiting outstanding mechanical properties. In order to estimate the mechanical behavior of potential alloys, thermodynamic and ab initio calculations were utilized in this work to investigate phase stability and stacking fault energy (SFE) for (Fe50Mn30Co10Cr10)-xBx (x = 0, 5, 7, 10, and 15 at.%) systems. Thermodynamic experiments revealed two structural variations of borides, M2B(C16) with a tetragonal structure and M2B(CB) with an orthorhombic structure. Borides precipitate when boron content increases, and the FCC matrix becomes deficient in Mn and Cr. According to ab initio calculations, the presence of boron in the FCC and HCP structures primarily disrupts the surroundings of the Fe and Mn atoms, resulting in an increased distortion of the crystal lattice. This is related to the antiferromagnetic condition of the alloys. Furthermore, for alloys with a low boron concentration, the stacking fault energy was found to be near 20 mJ/m2 and greater than 50 mJ/m2 when 10 and 15 at.% boron was added. As boron concentrations increase, M2B borides are formed, generating changes in the matrix composition prone to fault-induced phase transitions that could modify and potentially impair mechanical properties.