Wanda Vargas

Comparative prevalence of sensitization to common animal, plant and mould allergens in subjects with asthma, or atopic dermatitis and/or allergic rhinitis living in a tropical environment

Background and objectives Current information suggests that the expression of allergic diseases is determined by the exposure and nature of the allergen. The objectives of the present study were to determine if the nature of allergenic exposition to animal, plant or fungal allergens influenced the clinical manifestations of atopic dermatitis (AD), allergic rhinitis (AR) or asthma (AS) in patients living in a tropical environment. The prevalence and degree of sensitization to these allergens were analysed by age and gender.

Factors associated with breast cancer in Puerto Rican women

Background: Breast cancer (BC) is the most common cancer afflicting Puerto Rican women and accounts for more cancer-related deaths in this population than any other cancer. Methods: Demographic, anthropometric, family history, and lifestyle data, as well as DNA repair capacity (DRC), were compared in 465 BC cases and 661 controls. Crude and multiple logistic regression-derived adjusted odds ratios were used as indicators of the associations between BC and the variables under study. Results: A low DRC level, aging (>61 years), family history of BC, and low education level had statistically significant associations with increased BC risk. Endometriosis, full-term pregnancy at an earlier age, higher parity, hysterectomy before age 50, multivitamin and calcium intake, and longer duration of breastfeeding significantly decreased BC risk. Conclusions: This study discusses the major risk factors for BC in Puerto Rico (PR). Because many of these findings represent modifiable risk factors, they can translate into public health initiatives to lower BC risk. In addition, the possibility of using DRC as a simple screening tool for BC risk is explored.

The association of DNA Repair with breast cancer risk in women. A comparative observational study

BackgroundPrevious studies have found a link between a low DNA repair capacity (DRC) level and increased cancer risk. Our aim was to assess the statistical association of DRC level and breast cancer (BC) using a case–control epidemiological study in a Hispanic community.MethodsWe conducted a comparative observational study to assess the validity of DRC in detecting BC in 824 women throughout Puerto Rico. Over a 6-year period, we compared 285 women newly diagnosed with BC to 539 without BC. DRC levels were measured in lymphocytes by means of a host-cell reactivation assay. We assessed the sensitivity, specificity, and association using the receiver operating characteristic curve analysis. Multiple logistic regression-adjusted odds ratios were estimated with 95% confidence level to measure the strength of the association of DRC and BC after adjusting for all confounders simultaneously.ResultsCompared to women without cancer, women with BC showed an average decrease of 60% in their DRC levels (p < 0.001). Validity of the association of DRC as a measure of BC risk showed a sensitivity of 83.2% and specificity of 77.6% (p < 0.0001).ConclusionsOur results support the usefulness of DRC level as a measure of BC risk. Additional studies in other populations are needed to further verify its usefulness.

Estrogen Receptor Expression Is Associated with DNA Repair Capacity in Breast Cancer.

Estrogen-receptor-positive (ER+) tumors employ complex signaling that engages in crosstalk with multiple pathways through genomic and non-genomic regulation. A greater understanding of these pathways is important for developing improved biomarkers that can better determine treatment choices, risk of recurrence and cancer progression. Deficiencies in DNA repair capacity (DRC) is a hallmark of breast cancer (BC); therefore, in this work we tested whether ER signaling influences DRC. We analyzed the association between ER positivity (% receptor activation) and DRC in 270 BC patients, then further stratified our analysis by HER2 receptor status. Our results show that among HER2 negative, the likelihood of having low DRC values among ER- women is 1.92 (95% CI: 1.03, 3.57) times the likelihood of having low DRC values among ER+ women, even adjusting for different potential confounders (p<0.05); however, a contrary pattern was observed among HER2 positives women. In conclusion, there is an association between DRC levels and ER status, and this association is modified by HER2 receptor status. Adding a DNA repair capacity test to hormone receptor testing may provide new information on defective DNA repair phenotypes, which could better stratify BC patients who have ER+ tumors. ER+/HER2- tumors are heterogeneous, incompletely defined, and clinically challenging to treat; the addition of a DRC test could better characterize and classify these patients as well as help clinicians select optimal therapies, which could improve outcomes and reduce recurrences.

Measuring asthma disparities in Hispanics: adherence to the national guidelines for asthma treatment in emergency departments in Puerto Rico

BACKGROUND Puerto Rico has the highest prevalence of asthma in the United States. Currently, there are no data on actual care given to asthmatic patients. OBJECTIVE To determine the prevalence of documented adherence to the 1997 National Asthma Education Prevention Program guidelines regarding care given in emergency departments (EDs) in Ponce, Puerto Rico. METHODS A case series was conducted using 6,002 ED records with a physician-based diagnosis of asthma for 1999 through 2001. RESULTS A history of asthma attack was documented in 82.0% of the cases and in all age groups. In-home beta-agonist use was recorded in only 5.7% of the medical records. Documentation of previous admissions to the ED and the intensive care unit were found in 3.5% and 0.33% of the records, respectively. Nocturnal symptoms before the ED visit were found in only 6.4% of the records, and asthma treatment at home was found in 39.9%. Accessory muscle retraction was documented in 99.1% of the cases, and oxygen saturation was found in 23.2%. Treatment with nebulized beta-agonist was found in 72.1% of the records, and intravenous or oral corticosteroid use was found in 84.1%. Follow-up appointments were detected in 64.8% of the cases, and referrals to specialists were given in only 5.3%. Rate ratios between our data and those of other researchers indicate that there are geographical differences in compliance with the guidelines. CONCLUSION Of the variables tested, only one had acceptable levels of compliance, as evidenced in the patients records, indicating that there are alarming differences in ED evaluation and treatment compared with the 1997 National Asthma Education Prevention Program guidelines.

Abstract 3286: Correlation between vitamin D levels and DNA repair capacity in breast cancer patients stratified by molecular subtypes

Vitamin D exists as vitamin D2 and D3, which are metabolized to 25-hydroxyvitamin D [25(OH)D], the major circulating vitamin D metabolite. Besides its physiological functions, vitamin D levels have also been studied as a risk factor for several hormonal cancers including breast cancer (BC). Worldwide, BC accounts for nearly a quarter of all cancers in women. Nutritional studies report that vitamin D intake is associated with a lower BC risk. Several discrepancies exist regarding the role of serum vitamin D in BC risk. While some studies report BC risk reduction by vitamin D only in premenopausal, others propose that it only occurs in postmenopausal women. BC tumors may (+) or may not (-) have three hormonal receptors: estrogen (ER), progesterone (PR), and HER2. Based on their status, four principal molecular BC subtypes have been identified: luminal A (ER+/−, PR+/−, HER2-), luminal B (ER+/−, PR+/−, HER2+), HER2+ (ER−, PR−, HER2+), and triple negative (TN) (ER−, PR−, HER2−). If BC is analyzed in terms of molecular subtypes, low vitamin D levels have been associated with aggressive phenotypes and worse prognosis. Vitamin D also influences estrogen synthesis. Since we have previously shown that a low DNA repair capacity (DRC), measured through the nucleotide excision repair pathway, is a risk factor for BC and vitamin D has also been found to affect DNA repair, the focus of this study is to examine the role of plasma vitamin D levels and DRC in BC. The main aim is to elucidate whether there is an association between vitamin D and DRC levels among the four molecular BC subtypes. We hypothesize that a negative correlation between 25(OH)D and DRC levels will be observed among these subtypes. As an initial effort, 47 BC cases and 20 controls without BC were selected from our large BC cohort. DRC was measured in lymphocytes of untreated women using the host cell reactivation assay. Pathology reports were examined to divide BC cases according to their molecular BC subtype: luminal A (n=13), luminal B (n=11), HER2+ (n=10), and TN (n=13). Plasma 25(OH)D levels were measured using the UniCel DxC System at a CLIA-certified lab. Our results show a negative correlation between 25(OH)D and DRC levels (p=0.04). Statistically significant differences were found for vitamin D levels among the different groups (p=0.0019, ANOVA). Moreover, higher 25(OH)D levels (47.97±2.4 ng/mL) were found in ER- BC cases (p=0.03, t-test). When comparing vitamin D levels in BC subtypes, a significant difference was found in HER2+ and TN groups when compared with the control group (p Citation Format: Carmen Ortiz, Jarline Encarnacion, Ralphdy Vergne, Wanda Vargas, Jaime Matta. Correlation between vitamin D levels and DNA repair capacity in breast cancer patients stratified by molecular subtypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3286. doi:10.1158/1538-7445.AM2017-3286

Abstract 1899: Let-7b overexpression is associated with higher nucleotide excision repair pathway in women with breast cancer

Nucleotide Excision Repair (NER) is a critical pathway involved in breast cancer (BC). We have previously published that a low DNA repair capacity (DRC) is associated with a higher risk of BC in Puerto Rican women. In recent years we have focused our investigations on microRNAs (miRNAs) that are differentially associated with a low and a high DRC in women with BC and controls. A discovery experiment with 29 BC cases and 27 controls produced 12 candidate miRNAs associated with DRC including let-7b. The main objective of this study was to elucidate if there is a correlation between let-7b expression and specific DRC levels. Let-7b belongs to a miRNA family with tumor suppressor activity that targets oncogenic genes such as Ras, Myc, and HmgA2. DRC was measured in lymphocytes by means of a host cell reactivation assay with a luciferase reporter gene. We isolated miRNAs from plasma of 145 Puerto Rican women with and without BC (recently diagnosed, untreated cases and controls) using the miRNeasy kit (Qiagen). These women were divided into four groups according to their DRC level: high (>3.8%) and low ( Citation Format: Jarline Encarnacion, Carmen Ortiz, Ralphdy Vergne, Wanda Vargas, Jaime L. Matta. Let-7b overexpression is associated with higher nucleotide excision repair pathway in women with breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1899.

Abstract 2394: The role of DNA repair in breast cancer risk and recurrence

BACKGROUND: Breast cancer (BC) is a complex disease that is caused by multiple factors. Deficits in DNA repair capacity (DRC) are known to cause certain familial BC, and dysregulation of DRC develops with progressive carcinogenesis. However, the effect of DRC on carcinogenesis of sporadic breast tumors has not been well characterized_and the factors associated with DRC variability are still poorly understood. DNA repair is integral to maintain genomic integrity, and carcinogenesis occurs when efficient, effective DNA repair is impaired. Our laboratory has just finished the recruitment of nearly 1,200 women in a seven-year molecular epidemiology study focused on the role of DRC as a risk factor for BC. OBJECTIVE: Our aim is to present key findings on the role of DRC as a risk factor for BC and its potential association with BC recurrence. METHODS: A personal interview was conducted for soliciting information on BC risk factors. Among the 493 BC cases and 683 controls the DRC was measured in lymphocytes using a host cell reactivation assay with a luciferase reporter gene. We stratified the women with BC using the median of the DRC level and selected 70 women with a low DRC level ( DRC that, on average, is 51% lower than women without BC (P Citation Format: Jaime L. Matta, Erick Suarez, Wanda Vargas, Carmen Ortiz, Manuel Bayona, Luisa Morales. The role of DNA repair in breast cancer risk and recurrence. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2394. doi:10.1158/1538-7445.AM2014-2394

Abstract 1206: HER2/neu positive receptor status is associated with a low DNA repair capacity in women with breast cancer

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Hormone receptor status are now routinely used for therapy selection in breast cancer (BC). Estrogen receptor status is routinely use for the selection of tamoxifen adjuvant therapy after surgery. Substantial evidence now indicates that patients with BC tumors that have overexpression of the HER2/neu receptor have generally a poor prognosis. Approximately 15-20 percent of BC patients have an amplification of the HER2/neu gene. Overexpression of HER2/neu is associated with increased BC recurrence and worse prognosis. Because of its prognostic role as well as its ability to predict response to trastuzumab (Herceptin), breast tumors are routinely checked for overexpression of HER2/neu. Strategies targeting DNA repair defects for the treatment of patients with triple-negative and BRCA mutation-associated BC have received much attention recently, however the relationship between HER2/neu receptor status and the phenotypic expression of DNA repair capacity (DRC) measured in lymphocytes has never been previously examined. DRC is an important risk factor for several types of cancer including BC. In this study, we examined the association between BC and DRC and the status of estrogen, progesterone and HER2/neu receptors. Our main objective was to determine if levels of DRC measured in lymphocytes using a host cell reactivation assay with a luciferase reporter gene are associated with receptor status. The estrogen, progesterone and HER2/neu receptor status, DRC levels, and other selected covariates were compared among 125 Hispanic women with histopathologically confirmed BC. After variable transformation, the mean DRC was compared between positive and negative HER2/neu BC patients using the t-test and the Wilcoxons test to assess the statistical significance of the mean DRC difference. Crude and multiple logistic regression adjusted odds ratios (OR) were used as measures of association when compared HER2/neu (+) with (−) BC patients. The two-sided Wald test was used to assess the adjusted OR statistical significance. BC women with a HER2/neu (+) (n=14) had 4.1 times more odds of having a low DRC (< 1.78) compared with those that were HER2/neu (−) (n=65): (OR = 4.3 (95% CI 1.1, 16.6) p = 0.047. The average DRC in controls without BC was 6.10% (n=560). Women with BC that were HER2/neu (+) had an average DRC of 1.6% while BC patients that were HER2/neu (−) had 2.4%, this difference was significant (p=0.008). No significant differences were evident in regards to the association between DRC and the status of estrogen and progesterone receptors (double negatives) nor with triple negative receptor status (estrogen, progesterone and HER2/neu).These results indicate that low DRC could, at least partially explain, why HER2/neu (+) tumors are more aggressive. Supported by the NCI Diversity Training Branch of the Center to Reduce Cancer Health Disparities through the MBRS SCORE Program (Grant SO6 GM008239-23). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1206. doi:10.1158/1538-7445.AM2011-1206

Abstract 976: Consumption of vitamins and calcium reduces breast cancer risk by their regulation of the DNA repair capacity

Background- Breast cancer (BC) is the most common cancer in women with over one million new cases diagnosed annually worldwide. The capacity of the DNA to repair itself (DRC) is a complex biological process involving over 200 proteins. This process involves at least five pathways and is critical in maintaining genomic stability. The objective of this study was to examine the association of DRC and BC risk in terms of consumption of vitamin and calcium supplements by means of a large scale case-control study. Methods.- This was an incident-case case-control study design involving Puerto Rican women. The selection of potential predictors under study was based on previous published research in BC including information on vitamins, calcium, and variables that could provide an estimate of BC risk including age, BMI, family history, gynecological history, hormonal and environmental factors. The host reactivation assay with a luciferase reporter gene was used to measure the DRC in the lymphocytes from all participants. Cases were compared to controls, regarding diet supplement intake, DRC, and other selected covariates. The crude and multiple logistic regression adjusted Odds Ratio (OR) were used as measures of association and the 95% confidence interval of the OR was utilized to asses the precision of this estimate. Results.- A total of 268 breast cancer cases and 457 controls were included in this analysis. Statistically significant associations were found between BC and ageing, low DRC levels, family history of BC, and no breastfeeding. Vitamins and calcium intake were found to be protective reducing 30% and 40% the odds of having BC respectively. Calcium reduced considerably its protective effect becoming negligibly and not statistically significant when DRC was included in the logistic regression model. This suggests that DRC explains this association. In contrast, vitamin9s intake did not show an important change in the association with BC when adjusting for DRC. Calcium and vitamins’ intake were strongly associated with higher levels of DRC. Discussion.- Vitamins and calcium intake are protective for breast cancer and are associated with higher DRC levels. Vitamins’ intake is an independent protective factor for BC while the protective effect of calcium may be explained by an increased DRC. DRC can be used to monitor the protective effect of calcium in terms of breast cancer risk. This study is supported by grants from the NCI Center to Reduce Health Disparities and NIH-MBRS Program grant #: S06 GM008239-23. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 976.