Sugar-Sweetened Beverages Consumption and Breast Cancer in Premenopausal and Postmenopausal Women.

BACKGROUND: The consumption of sugar-sweetened beverages (SSB), of which Mexico is a large consumer, has been associated with the risk of breast cancer. We assessed the association between SSBs consumption and breast cancer risk in pre- and postmenopausal women. METHODS: We performed a multicenter population-based case-control study in Mexico City, Monterrey, and Veracruz. We recruited 1,000 cases and 1,074 controls; all participants were pre- or postmenopausal women between 35 and 69 years of age. Diet before symptoms onset was assessed using a food frequency questionnaire. We conducted a multivariable-adjusted conditional logistic regression analysis stratified by menopausal status. RESULTS: For premenopausal women, after adjusting for matching characteristics, total energy intake and all potential confounders, the odds of having breast cancer in women who drank one or more SSBs servings per day showed 1.78 times the odds of those who drank one or fewer SSBs servings per month [OR = 1.78; 95% confidence interval (CI), 1.06-3.01]. For postmenopausal women, the corresponding model was not statistically significant (OR = 1.38, 95% CI, 0.84-2.25). We also observed higher consumption of SSBs among pre- than in postmenopausal women (23.3% and 17.4%, respectively among controls in the highest consumption category (≥1 per day). CONCLUSIONS: Our results suggest that SSBs consumption increases the risk of developing breast cancer, particularly in premenopausal women. IMPACT: Given the consumption of SSBs, of which Mexico is a large consumer, these results can support public policies to discourage the consumption of SSBs.

Phylogenetic origin of Helicobacter pylori pathogenicity island and risk of stomach cancer and high-grade premalignant gastric lesions.

Infection by Helicobacter pylori (Hp) has been causally linked to risk of gastric cancer (GC). The coevolution of Hp and humans shaped the risk of GC as our species left Africa and migrated to the other continents. Latin America (LatAm) is a high GC incidence region where Hp evolved uniquely in the 500 years since European colonization. Differential virulence of the Hp cagA -pathogenicity island (cagPAI) by ancestral origin has been reported. We hypothesized that Hp phylogenetic origin might play a role in determining GC risk in LatAm. We used genotypes of 50 Hp genetic variants mapping to the Hp cagPAI, studied in 1220 subjects from Venezuela, Colombia, Mexico and Paraguay, who were infected with cagA-positive Hp, including 150 GC, 177 high-grade premalignant lesions (HGPMLs) and 893 low-grade premalignant lesions. We estimated the phylogenetic origin of Hp cagPAI in all study subjects by use of the STRUCTURE software and principal component analysis (PCA) and tested whether the estimated African ancestry percentage was associated with the risk of GC or HGPML. African ancestral component estimates by STRUCTURE and PCA were highly correlated. STRUCTURE-based African origin estimate was not significantly associated with the risk of HGPML, but it was inversely associated with GC risk: the OR associated with the continuous values of African component was 0.09 (95% CI, 0.01-0.85; P = 0.035). Similar trends were observed for GC with PCA-based estimates, but the association was not statistically significant. These results suggest that Hp ancestral origin may play a role in gastric carcinogenesis.

Farmacogenética en el cáncer de mama: implicaciones de los genes del citocromo p450 en la supervivencia libre de la enfermedad en las mujeres jóvenes / Pharmacogenetics in breast cancer: Implications of cytochrome p450 genes in disease-free survival in young women

Las mujeres jóvenes (≤40 años) con cáncer de mama suelen tener un peor pronóstico que las mujeres posmenopáusicas, con repercusiones reproductivas y familiares importantes. El tratamiento quimioterapéutico, así como la hormonoterapia, pueden mejorar el pronóstico y la supervivencia libre de enfermedad (SLE); sin embargo, la capacidad individual de metabolizar los fármacos puede modificar la respuesta al tratamiento. Las diferencias interpersonales de esta capacidad tienen una explicación en las variaciones de los genes que codifican las enzimas que metabolizan los quimioterapéuticos y las hormonas endógenas y exógenas. Los genes del citocromo P450 (CYP450), CYP3A4, CYP2B6, CYP2D6 y CYP2C19, están involucrados en el metabolismo de los estrógenos y la ciclofosfamida, los taxanos y el tamoxifeno. La presente revisión expone la evidencia científica del efecto de los polimorfismos funcionales de estos genes sobre la SLE, y sus implicaciones, en las mujeres jóvenes con cáncer de mama. (AU)

Breast cancer prognosis tends to be worse in young women (≤40 years) than in postmenopausal women, with significant reproductive and family repercussions. Both chemotherapy and hormonal therapy can improve prognosis and disease-free survival but treatment response may be influenced by the individual's ability to metabolize drugs. Individual differences in metabolic ability can be explained by variations in the genes encoding the enzymes that metabolize chemotherapeutic agents and hormones. The cytochrome P450 genes CYP3A4, CYP2B6, CYP2D6 and CYP2C19 are involved in the metabolism of estrogen, cyclophosphamide, taxanes, and tamoxifen. This review discusses the scientific evidence of the effect of functional polymorphisms in these genes on disease-free survival and overall survival and its implications for young women with breast cancer. (AU)

Energy homeostasis genes modify the association between serum concentrations of IGF-1 and IGFBP-3 and breast cancer risk.

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 (Pinteraction < 0.05, adjusted Pinteraction < 0.20). In addition, five SNPs in three genes (ADIPOQ rs182052, rs822391 and rs7649121, CARTPT rs3846659, and LEPR rs12059300) had an effect modification on the association between IGFBP-3 serum concentration and breast cancer risk (Pinteraction < 0.05, adjusted Pinteraction < 0.20). Our findings showed that variants of energy homeostasis genes modified the association between the IGF-1 or IGFBP-3 serum concentration and breast cancer risk in premenopausal women. These findings contribute to a better understanding of this multifactorial pathology.

TAS2R38 polymorphisms, Helicobacter pylori infection and susceptibility to gastric cancer and premalignant gastric lesions.

BACKGROUND: Gastric cancer is worldwide the fourth more common cancer type by incidence, and the third by mortality. We analyzed three missense variants of TAS2R38 gene: rs713598 (A49P), rs1726866 (V262A), and rs10246939 (I296V). These variants and their combination in haplotypes (proline, alanine and valine/tasters or alanine, valine and isoleucine/nontasters) and diplotypes are responsible for individual differences in bitter perception. The single-nucleotide polymorphisms and the related phenotypes are known to be associated with susceptibility to Gram-negative bacterial infections, such as Helicobacter pylori , and with risk of various cancer types. An association between intermediate tasters (as defined by TAS2R38 diplotypes) and increased risk of gastric cancer was reported in a Korean population. METHODS: We analyzed 2616 individuals of Latin American origin, representing the whole spectrum of lesions from gastritis to gastric cancer. RESULTS: Comparing cancer cases vs. noncancers we observed a decrease in risk associated with heterozygous carriers of rs10246939 ( P = 0.006) and rs1726866 ( P = 0.003) when compared with homozygotes of the more common allele. Also, the analysis of diplotypes/phenotypes reflected the same association, with super-tasters showing a borderline increased risk of developing gastric cancer compared to medium-tasters [odds ratio (OR) = 1.63; 95% confidence interval (CI), 1.04-2.56; P = 0.033]. Also, nontasters showed an increased risk when compared to medium-tasters although not reaching statistical significance (OR = 1.58; 95% CI, 0.80-2.87; P = 0.203). We also tested the interactions between the TAS2R38 genotypes and H. pylori cagA status in a subset of samples and found no interaction. CONCLUSION: In conclusion, our results suggest only a modest contribution of TAS2R38 gene genetic variability in gastric cancer etiology.

Detection of Epstein-Barr Virus DNA in Gastric Biopsies of Pediatric Patients with Dyspepsia.

In this study, we assessed the presence of Epstein-Barr virus (EBV) in gastric samples derived from pediatric patients with dyspeptic symptoms, aiming to understand whether EBV participates in the development of early gastric lesions influencing chronic inflammation, in conjunction with the Helicobacter pylori (Hp) bacterium. We analyzed EBV load in 236 gastric biopsies derived from 186 pediatric patients with chronic dyspepsia and compared it with EBV serology, Hp load and serology, and with immune cell infiltration. We found that 7.5% of patients were positive for EBV load, ranging from 240 to 29,685 genomic copies/µg of DNA. Hp genomic sequences were found in 24.7% of patients. EBV positive samples did not correlate with Hp status and were characterized by absent to moderate immune cell infiltration. To our knowledge, this is the first study addressing EBV load in the stomach in a large cohort of pediatric patients with dyspeptic symptoms, providing evidence of EBV localization in the gastric mucosa in early inflammatory lesions. The lack of correlation between EBV and both Hp infection and inflammation is perhaps explained by independent pathogenic mechanisms or because of the randomness of the gastritis sampling. This is also supported by a moderate association between EBV load and serology.

Genetic polymorphisms in the cag pathogenicity island of Helicobacter pylori and risk of stomach cancer and high-grade premalignant gastric lesions.

Helicobacter pylori (Hp) infects the stomach of about half of the human population and is strongly associated with the risk of gastric cancer (GC) and its premalignant precursors. The cag pathogenicity island (cagPAI) is a region of the Hp genome encoding for key molecular machinery involved in the infection process. Following a sequencing study, we selected 50 genetic polymorphisms located in seven cagPAI genes and tested their associations with the risk of advanced gastric premalignant lesions and GC in 1220 subjects from various Latin American populations showing the whole spectrum of phenotypes from gastritis to GC. We found that three polymorphisms of cagA are associated with the risk of advanced gastric premalignant lesions (incomplete intestinal metaplasia [ie, Type 2 and 3] or dysplasia), and that six polymorphisms located in cagA, cagL and cagI were associated with risk of GC. When corrected for multiple testing none of the associations were statistically significant. However, scores built by integrating the individual polymorphisms were significantly associated with the risk of advanced gastric premalignant lesions and GC. These results have the potential of establishing markers for risk stratification in the general population, in view of targeting Hp eradication to high-risk population groups.

Risk factors for gastric precancerous and cancers lesions in Latin American counties with difference gastric cancer risk.

OBJECTIVE: To evaluate the risk factors associated with pre-neoplastic lesions and gastric cancer in countries with different cancer risk in Latin America. METHODS: 1222 questionnaires of risk factors related to pre-neoplastic lesions and gastric cancer were obtained from patients from Mexico (N = 559), Colombia (N = 461) and Paraguay (N = 202), who were treated at the gastroenterology or oncology service of participant hospitals. In addition, biopsies specimens to establish histological diagnosis and blood to detect IgG antibodies against Helicobacter-pylori (H. pylori) whole-cell antigens and CagA protein using an ELISA were collected. These consisted of 205 gastric cancer, 379 pre-neoplastic (intestinal metaplasia (IM) / atrophic gastritis) and 638 control (normal /non-atrophic gastritis) cases. The odds ratio (OR) and 95% confidence intervals (CI) associated with potential risk factors were estimated by polynomial logistic regression model. RESULTS: Seropositivity to H. pylori was associated with risk of pre-neoplastic lesions, with OR = 1.9 (CI 95% 1.2-2.9; p = 0.006). Grain / cereal intake (OR = 1.6, 95% CI 1.0-2.5 ; p = 0.049) and egg intake (OR = 1.7 95% CI 1.1-2.6 ; p = 0.021) were related to gastric cancer. Among, people who did not developed gastric cancer, smoking more than five cigarette per day had the highest risk of being infected by H. pylori (OR = 1.9; CI 95% 1.1-3.3 ; p = 0.028). CONCLUSION: The present study in Latin American countries confirmed that similar environmental factors such as smoking and grain/cereal consumption were associated with H. pylori infection and its induced gastric lesions as reported in other regions where dominant H. pylori strains differ.

[Trends in the prevalence of ARIs and ADDs in early childhood and associated factors: Ensanut 2012 and 100k.] / Tendencias en la prevalencia de IRA y EDA en la primera infancia y factores asociados: Ensanut 2012 y 100k.

OBJECTIVE: To compare the prevalence of acute respiratory infections (ARI) and acute diarrheal disease (ADD) among children younger than five years of age living in localities with less than 100 000 inhabitants in Encuesta Nacional de Salud y Nutrición (Ensanut) 2012 and Ensanut 100k (2018). In Ensanut 100k, we evaluate the associated factors. MATERIALS AND METHODS: Analysis of both surveys and of the Mexican Meteorological System. RESULTS: The estimated prevalence of ARI was 45.1% in 2012 vs. 32.9% in 2018. The decrease was significant among medium and high-income households. There were no changes in trends for ADD. Among households with lower EC, ARI was associated with roofing material, temperature, and rainy precipitation while ADD was associated with lack of piped water. CONCLUSIONS: The estimated prevalence of ARI has decreased in medium and high income households. Some households and weather conditions are associated with ARI and ADD.

OBJETIVO: Estimar y comparar las prevalencias de infec- ciones respiratorias agudas (IRA) y enfermedades diarreicas agudas (EDA) en menores de cinco años, residentes en localidades con menos de 100 000 habitantes, mediante análisis de la Encuesta Nacional de Salud y Nutrición (Ensanut) 2012 y la Ensanut 100k (2018). En la Ensanut 100k se evaluaron los factores asociados con IRA y EDA. MATERIAL Y MÉTODOS: Análisis de ambas encuestas e información meteorológica de la Comisión Nacional del Agua. RESULTADOS: La prevalencia global estimada de IRA fue de 45.1% en 2012 vs. 32.9% en 2018. La disminución fue significativa en hogares de medianas y mayores capacidades económicas (CE). No se observaron cambios significativos para las EDA. En hogares con menores CE, las IRA se asociaron con material del techo y temperatura y las EDA con privación de agua entubada. CONCLUSIONES: Entre 2012 y 2018, la prevalencia de IRA disminuyó en hogares de medianas y mayores CE. Algunas condiciones de vivienda y meteorológicas se asocian con IRA y EDA.

Tendencias en la prevalencia de IRA y EDA en la primera infancia y factores asociados: Ensanut 2012 y 100k / Trends in the prevalence of ARIs and ADDs in early childhood and associated factors: Ensanut 2012 and 100k

Resumen: Objetivo: Estimar y comparar las prevalencias de infecciones respiratorias agudas (IRA) y enfermedades diarreicas agudas (EDA) en menores de cinco años, residentes en localidades con menos de 100 000 habitantes, mediante análisis de la Encuesta Nacional de Salud y Nutrición (Ensanut) 2012 y la Ensanut 100k (2018). En la Ensanut 100k se evaluaron los factores asociados con IRA y EDA. Material y métodos: Análisis de ambas encuestas e información meteorológica de la Comisión Nacional del Agua. Resultados: La prevalencia global estimada de IRA fue de 45.1% en 2012 vs. 32.9% en 2018. La disminución fue significativa en hogares de medianas y mayores capacidades económicas (CE). No se observaron cambios significativos para las EDA. En hogares con menores CE, las IRA se asociaron con material del techo y temperatura y las EDA con privación de agua entubada. Conclusiones: Entre 2012 y 2018, la prevalencia de IRA disminuyó en hogares de medianas y mayores CE. Algunas condiciones de vivienda y meteorológicas se asocian con IRA y EDA.

Abstract: Objective: To compare the prevalence of acute respiratory infections (ARI) and acute diarrheal disease (ADD) among children younger than five years of age living in localities with less than 100 000 inhabitants in Encuesta Nacional de Salud y Nutrición (Ensanut) 2012 and Ensanut 100k (2018). In Ensanut 100k, we evaluate the associated factors. Materials and methods: Analysis of both surveys and of the Mexican Meteorological System. Results: The estimated prevalence of ARI was 45.1% in 2012 vs. 32.9% in 2018. The decrease was significant among medium and high-income households. There were no changes in trends for ADD. Among households with lower EC, ARI was associated with roofing material, temperature, and rainy precipitation while ADD was associated with lack of piped water. Conclusions: The estimated prevalence of ARI has decreased in medium and high income households. Some households and weather conditions are associated with ARI and ADD.

Synergistic action of folate intake and testosterone associated with breast cancer risk.

The amount of irreparable DNA damage is a function of the rate of cell division, and the association between sex hormones and the risk of breast cancer has been explained by an increase in cell division. Folate intake insufficiency leads to disturbances in DNA replication and DNA repair. We hypothesized that folate intake insufficiency and high serum concentrations of sex hormones act synergistically on the risk of breast cancer. The aim of this study was to investigate the interaction between sex hormones (exposure of interest A) and dietary folate intake (exposure of interest B) on the risk of breast cancer. We included 342 breast cancer primary postmenopausal cases and 294 controls obtained from a large population-based case-control study. Multiple conditional logistic regression models were used for the analysis and interactions were tested. The joint effect of the lowest dietary folate intake (T1 < 259.40 mg/d) and the highest serum concentration of testosterone (T3 ≥ 0.410 on the risk of breast cancer was odds ratio = 9.18 (95% confidence interval 2.56-32.88) when compared to the lowest-risk category, namely, the group of women with the highest dietary folate intake (T3 > 381.29 mg/d) and the lowest serum concentration of testosterone (T1 ≤ 0.25 pg/mL). There were some indications that the estimated join effect was greater than the product of the estimated effects alone (P = .001). These findings have important public health implications with respect to reducing the risk of the most frequent cancer in women worldwide.

Polymorphisms in IL-10 and TGF-ß gene promoter are associated with lower risk to gastric cancer in a Mexican population.

BACKGROUND: Helicobacter pylori infection is recognized as the main risk factor for gastric cancer (GC), the fifth most common neoplasia worldwide. H. pylori interacts with the immune system, disrupting the cytokine network and inducing chronic inflammation. This work aimed to evaluate the association between single nucleotide polymorphisms (SNPs) in selected cytokine gene promoters and GC. METHODS: The study included 359 subjects, 125 GC patients, 109 intestinal metaplasia (IM) patients and 125 asymptomatic controls. DNA was extracted from white blood cells and nine SNPs in cytokine gene promoters were genotyped using predesigned 5'-endonulease assays. The association of the SNPs with IM and GC was evaluated using multinomial regression models. RESULTS: Both genotypes, TC (OR = 0.51, 95% CI = 0.27-0.98) and TT (OR = 0.42, 95% CI = 0.20-0.91) in the locus - 509 of the TGF-ß promoter were significantly associated with GC. The TT genotype in the locus - 819 of the IL-10 promoter was also significantly associated with GC (OR = 0.37, 95% CI = 0.17-0.81). No significant association was found with SNPs IL-4 -590 T/C (rs1800629), IL-6 -573G/C (rs1800796), IL-10 -592C/A (rs1800872), IL-10 -1082A/G (rs1800896), and, IFN-γ -1615C/T (rs2069705). CONCLUSIONS: SNPs in TGFß (- 509 C/T, rs1800469) and IL-10 (- 819 C/T, rs1800871) promoters were associated with a lower risk for GC in a Mexican population.

Impact of invasive lobular carcinoma on long-term outcomes in Mexican breast cancer patients.

PURPOSE: The aim of this study was to compare the difference in disease-free survival (DFS) and overall survival (OS) between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) in our Hispanic population with breast cancer (BC). METHODS: We retrospectively analyzed a database of 4533 non-metastatic BC patients treated for BC at the National Cancer Institute in Mexico (INCan) between 2006 and 2016. We compared clinical characteristics, treatment and survival between women with invasive ductal and invasive lobular BC. We evaluated differences between survival curves with the log-rank test and used Cox's proportional hazards model for the multivariate analysis. RESULTS: Median follow-up time was 42.13 months (IQ25 25.2-IQ75 72.06). The median age was 50.9 years (IQ25 43.5-IQ75 59.8). DFS at 5 years was 80.8% for IDC versus 76.2% for ILC. 5 years OS was 88.7% for IDC versus 84.3% for ILC. Multivariate analysis showed that factors that negatively affected the 5-year DFS include: clinical stage III [hazard ratio (HR) 4.2, 95% CI 3.36-5.35; p < 0.001], triple negative phenotype (HR 1.4, 95% CI 1.08-1.81; p = 0.009), Ki67 ≥ 18 (HR 1.6, 95% CI 1.28-2.11; p < 0.001), and lobular histological type (HR 1.6, 95% CI 1.09-2.49; p = 0.017). Factors associated with a negative impact on OS were: clinical stage III (HR 4.5, 95% CI 3.15-6.54; p < 0.001), triple negative phenotype (HR 2.4, 95% CI 1.69-3.48; p < 0.001), and Ki67 ≥ 18% (HR 1.9, 95% CI 1.27-2.92; p = 0.02). CONCLUSION: Our results highlight the different biology of ILC and show that long-term prognosis in terms of DFS is not as favorable as previously reported.

Impact of Delayed Adjuvant Radiotherapy in the Survival of Women with Breast Cancer.

Objective Our objective was to determine whether a delay in adjuvant radiotherapy is related to a decrease in relapse-free survival and disease-specific survival of women with operable breast cancer. Methods Data on 1000 patients diagnosed with breast cancer were recorded. The cohort was divided into five groups according to the timing of radiotherapy: ≤30 days, 31 to 60 days, 61 to 90 days, 91 to 120 days, and >120 days. The relapse-free survival and disease-specific survival were also calculated in relation to the number of patients. Results This study found no statistical difference for delays in adjuvant radiotherapy in patients with early breast cancer, but we noted a statistical decrease in disease-specific survival in patients with locally advanced breast cancer receiving radiotherapy after a delay of at least 60 days. Conclusion Waiting times for radiotherapy should be as short as reasonably achievable, given the specific risk factors in the individual patient.

Polymorphisms in HLA-DQ genes, together with age, sex, and Helicobacter pylori infection, as potential biomarkers for the early diagnosis of gastric cancer.

BACKGROUND: Polymorphisms in inflammation-related genes are factors associated with the development of gastroduodenal diseases in Helicobacter pylori-infected individuals. MATERIALS AND METHODS: We aimed to analyze polymorphisms in HLA-DQ, together with other host and H. pylori variables as risk factors for precancerous and cancerous gastric lesions. 1052 individuals were studied, including nonatrophic gastritis (NAG), intestinal metaplasia (IM), gastric cancer (GC) or duodenal ulcer (DU) patients, and healthy volunteers. RESULTS: Patients with alleles DQA*01:01 (OR 0.78), *01:02 (OR 0.29), *01:03 (OR 0.31), and DQB*02:01/02 (OR 0.40) showed a reduced risk for GC. A multivariate logistic regression analyses showed that patients with homozygote genotypes DQA1*03:01 (OR 7.27) and DQA1*04:01 (OR 8.99) and DQB1*05:01:01 (OR 12.04) were at significantly increased risk for GC. Multivariate analyses also demonstrated that age (OR>10.0) and gender (OR>2.0) were variables that influenced significantly the risk for GC, while H. pylori infection (OR>2.5) increased the risk for IM. CONCLUSIONS: We identified HLA-DQ alleles associated with IM and GC, and confirm that age, sex, and H. pylori infection are variables that also influence the risk for disease. The use of multiple markers, HLA-DQ alleles, age, sex, and H. pylori infection may be useful biomarkers for the early diagnosis of patients with IM and GC.

The Western dietary pattern is associated with increased serum concentrations of free estradiol in postmenopausal women: implications for breast cancer prevention.

Little is known about the possible influence of food consumption on the serum concentrations of endogenous sex hormones in postmenopausal women. We evaluated the relationships of the Western dietary pattern with serum concentrations of free estradiol and testosterone of postmenopausal women to test the hypothesis that a highly Western dietary pattern is associated with high serum concentrations of these hormones. We used data from a representative subsample of 305 women from the control group of a population-based case-control study conducted in Mexico from 2004 to 2007. A Western dietary pattern index value was compared with log natural serum concentrations of testosterone and estradiol using multiple linear regression models. The median values of serum concentrations of free estradiol and testosterone were 0.26 pg/mL (interquartile range, 0.14-0.43) and 0.40 pg/mL (interquartile range, 0.30-0.70), respectively. A multiple linear regression model showed that for each unit increase in the Western dietary pattern index, there was a 16.2% increase in the serum concentrations of free estradiol (ß=0.15; 95% confidence interval [CI], 0.01-0.29); for each additional serving per week of chicken eggs, the increase was 31.0% (ß=0.27; 95% CI, 0.106-0.441); for each additional serving per week of red meat, the increase was 64.9% (ß=0.50; 95% CI, 0.01-1.01). There was no relationship found between dietary patterns and serum concentrations of free testosterone. The present findings suggest that intake of a Western diet, particularly of chicken eggs and meat, increases serum concentrations of free estradiol; these results have implications for breast cancer prevention.

Patterns of Adherence of Helicobacter pylori Clinical Isolates to Epithelial Cells, and its Association with Disease and with Virulence Factors.

BACKGROUND AND AIM: Adherence to the gastric epithelium is one of the most important steps of Helicobacter pylori to remain and cause disease. The aim of this study was to analyze whether H. pylori isolates from patients with different gastroduodenal diseases present differences in the pattern of adherence to gastric epithelial cells (AGS), in the ability to induce IL-8, and in the presence of virulence genes. METHODS: We tested 75 H. pylori strains isolated from nonatrophic gastritis, gastric cancer, and duodenal ulcer patients. The adhesion pattern and IL-8 induction were determined in AGS cells, and invasion of AGS cells was studied using a gentamicin protection assay. The IL-8 levels induced were determined by ELISA. RESULTS: Helicobacter pylori strains presented diffuse adherence (DA) and localized (LA) adherence patterns, similar to those described for enteropathogenic E. coli (EPEC), were observed in AGS cells. A DA pattern was observed in 57% and LA in 43% of the strains, and DA was more frequent in isolates from patients with gastric cancer (p = 0.044). Strains with a LA pattern induced higher levels of IL-8 (p = 0.042) in AGS cells. CONCLUSION: The adherence pattern was not associated with neither invasiveness nor with the presence of virulence genes. Our study shows that H. pylori strains present adherence patterns to AGS cells resembling those observed in EPEC and that these patterns may be associated with disease and with activity on AGS cells.

Epstein-Barr virus association with peptic ulcer disease.

Background. Helicobacter pylori (HP) infection and nonsteroidal anti-inflammatory drugs (NSAID) use are considered the main risk to develop peptic ulcer disease (PUD). However, PUD also occurs in the absence of HP infection and/or NSAID use. Recently, we have found evidence that Epstein-Barr virus (EBV) reactivation increases the risk to develop premalignant and malignant gastric lesions. Objective. To study a possible association between EBV and PUD. Methods. Antibodies against an EBV reactivation antigen, HP, and the HP virulence factor CagA were measured in sera from 207 Mexican subjects, controls (healthy individuals, n = 129), and PUD patients (n = 78, 58 duodenal and 20 gastric ulcers). Statistical associations were estimated. Results. Duodenal PUD was significantly associated with high anti-EBV IgG titers (p = 0.022, OR = 2.5), while anti-EBV IgA was positively associated with gastric PUD (p = 0.002, OR = 10.1). Conclusions. Our study suggests that EBV reactivation in gastric and duodenal epithelium increases the risk to develop PUD.

Polymorphisms in TLR9 but not in TLR5 increase the risk for duodenal ulcer and alter cytokine expression in the gastric mucosa.

Colonization of the gastric mucosa by Helicobacter pylori can lead to peptic ulcer and gastric adenocarcinoma. TLRs are signaling receptors involved in the recognition of microorganisms, and polymorphisms in their genes may influence the innate and adaptive immune response to H. pylori, affecting the clinical outcomes of the infection. We assessed the association between single nucleotide polymorphisms in TLR9 and TLR5 and gastroduodenal diseases. All patients were genotyped by allelic discrimination in regions 1174C>T and 1775A>G of TLR5 and -1237T>C and 2848G>A of TLR9. The 2848A allele of TLR9 was more frequent in duodenal ulcer and showed an association of risk with this pathology. Polymorphisms in TLR5 were not found to be associated with disease. Patients with polymorphisms in TLR9 and TLR5 expressed significantly lower levels of IL-1ß and TNF-α, whereas polymorphisms in TLR5 also decreased the expression of IL-6 and IL-10. Our findings suggest that 2848G>A polymorphism in TLR9 increases the risk for the development of duodenal ulcer probably by modifying the inflammatory response to H. pylori infection. This is the first study to show an association of 2848A allele of TLR9 with duodenal ulcer and with altered expression of inflammatory cytokines in the gastric mucosa.

Toll-like receptors and cytokines are upregulated during Helicobacter pylori infection in children.

BACKGROUND AND AIM: Helicobacter pylori infection is mainly acquired during childhood, and establishes a chronic infection that may lead to peptic ulcer or gastric cancer during adulthood. Toll-like receptors (TLRs) are expressed by distinct cell types throughout the gastrointestinal tract, and play an important role in regulation of the innate immune response. Few works have addressed TLRs expression in gastric epithelia of adults, and scarce studies have done it in children. The aim of this work was to analyze the expression of TLR2, TLR4, TLR5, TLR9, and IL-8, IL-10 and TNF-α in the gastric mucosa of children with and without H. pylori infection. METHODS: Gastric biopsies were collected by endoscopy from 50 children with recurrent abdominal pain, 25 with H. pylori infection and 25 without infection. In the gastric biopsies the expression of TLRs and cytokines was studied by immunohistochemistry, and the degree of mucosal inflammation was determined using the Sydney system. RESULTS: We found that H. pylori infection was associated with a significant increased expression of TLRs 2, 4, 5 and 9, although expression varied between surface epithelia and glands. Epithelial cells expressing IL-8, IL-10 and TNF-α were increased in gastric mucosa of children with H. pylori infection. CONCLUSION: This study shows the gastric epithelia of children respond to H. pylori infection by increasing the expression of TLR2, TLR4, TLR5, TLR9 and the cytokines IL-8, IL-10 and TNF-α.