Association results between minor alleles of 467 variants incorportated in cross tissue gene expression prediction model for the gene of CRHR1.

PDF - 84KB, Joint effects of smoking and occupational exposure to aromatic amines and polycyclic aromatic hydrocarbons on the risk of bladder cancer (754 cases and 833 controls).

PDF - 84KB, Association of working in at-risk occupations with bladder cancer in men (609 cases and 665 controls) and women (145 cases and 168 controls) from EPIC.

PDF - 73KB, Joint effects of NAT2 acetylation status and occupational exposure to aromatic amines on the risk of bladder cancer (492 cases and 569 controls).

PDF - 63KB, NAT2 variants and bladder cancer risk for 607 cases and 695 controls nested in EPIC.

PDF - 80KB, Association of smoking and occupational exposure with bladder cancer by NAT2 acetylation in cases and controls from EPIC.

Objective. To evaluate the test-retest reliability and validity of the long-form International Physical Activity Questionnaire (IPAQ-long form). Materials and methods. A subsample of 86 teachers underwent telephone interviews and clinic visits in Mexico City. Through 22 months, physical activity (PA) levels were obtained from accelerometers (months 6 and 22) and IPAQ long-form (months 1, 3, 6, 9 and 12). Minutes per week of moderate (MPA), walking (WPA), vigorous (VPA) and moderate-to-vigorous physical activity (MVPA) were calculated for each intensity and domain. Variables were loga­rithmically transformed. Intra-class and Pearson correlations were used to determine the relationship between instru­ments. Results. Test-retest reliability of the average IPAQs long-form varied across intensities and domains (ranged from r= 0.24 to r= 0.65). Minutes per week of VPA and MVPA ac­celerometer 1 (AC1) were fairly associated to International Physical Activity Questionnaire-long form 3 (IPAQ3) (r= 0.60 and r= 0.31, respectively) one week apart. Conclusions. IPAQ long-form is fairly reliable for MVPA and valid for as­sessing MVPA and VPA in a subsample of Mexican teachers.

Rationale: Prenatal omega-3 fatty acids improve alveolarization, diminish inflammation, and improve pulmonary growth, but it is unclear whether these outcomes translate into improved postnatal lung function. Objective: We assessed the effect of prenatal supplementation with docosahexaenoic acid (DHA) on offspring lung function through 60 months of age. Methods: We included a cohort of 772 Mexican preschoolers whose mothers participated in a clinical trial (NCT00646360) of supplementation with DHA or a placebo from week 18-22 of gestation through delivery. Measurements: The children were followed after birth and anthropometric measurements and forced oscillation tests were performed at 36, 48, and 60 months of age. The effect of DHA was tested using a longitudinal mixed effect models. Results: Overall, mean (Standard Deviation) of the measurements of respiratory system resistance and respiratory system reactance at 6, 8, and 10 Hz during follow up period were 11.3 (2.4), 11.1 (2.4), 10.3 (2.2) and -5.2 (1.6), -4.8 (1.7), -4.6 (1.6), respectively. There were no significant differences in pulmonary function by treatment group. DHA did not affect the average lung function or the trajectories through 60 months. Conclusions: Prenatal DHA supplementation did not influence pulmonary function in this cohort of Mexican preschoolers.

TPS 684: Long-term health effects of air pollutants 1, Exhibition Hall, Ground floor, August 26, 2019, 3:00 PM - 4:30 PM Background. In Latin American more than 100 million people are exposed to air pollutants which, frequently are above WHO standards. Oxidative stress and airway inflammation are effects related to particulate matter (PM2.5) exposure. Objective: To evaluate PM2.5 concentrations and its association with oxidative stress and airway inflammation biomarkers in adolescents from Mexico. Methods: A longitudinal study was conducted in asthmatic and non-asthmatic adolescents with overweight and obesity along 2008 to 2011. PM2.5 concentrations were obtained from the Mexican air quality monitoring network and georeferencing. The 8-isoprostane, Glutathione (GSH), Oxidised glutathione (GSSG), nitrates, nitrites and nitric oxide (FeNO) were determined in exhaled vapor condensed. Statistical analyses of mixed models for longitudinal data, multiple regression models and interaction analysis between pollutants and biomarkers were performed. Results. In the airway inflammation was observed a significant increase for each unit change in the PM2.5 in the nonasthmatic children, in contrast with asthmatic, it was a decrement. For the asthmatic group each increase of 10 µg / m3 in PM2.5 was related to a 5.09 times of increase in Ln(FeNO) based on its predicted value, and the increment for non-asthmatic was of 4%. For the exhaled nitric oxide, an interaction between PM2.5 and the asthmatic state (p = 0.008) was observed. For nitrates and nitrates as well as in the 8-isoprostane, resulting in a PM2.5 positive effect on biomarkers: 0.11 logarithmic units (95 % CI: 0.02, 0.20) and 1.92 pg / mL (95 % CI: 0.59, 3.24), respectively. In the case of GSH, the effect on asthmatics was 22.03 points for each increase of 10 µg / m3 in PM2.5 and 0.48 points for the non-asthmatic group. Conclusion: Our results demonstrate that PM2.5 exposure increase inflammation and oxidative stress in obease non-asthmatic achieving levels similar to the asthmatic adolescents.

Background. Comorbidities occurring concurrently in breast cancer patients can be burdensome, as they may negatively influence time and stage of presentation. Objectives. To describe the comorbid health conditions among South African (SA) black women with and without breast cancer and to determine factors associated with advanced-stage presentation of breast cancer. Methods. A population-based case-control study on breast cancer was conducted in black women in Soweto, SA, the SABC (South Africa Breast Cancer) study. Lifestyle information and blood samples were collected from 399 women with histologically confirmed new cases of invasive primary breast cancer, recruited prior to any therapy, and 399 age- and neighbourhood-matched controls without breast cancer. We compared self-reported metabolic diseases, depression, anthropometric measurements, blood pressure, HIV status and point-of-care lipid and glucose levels between patients with breast cancer and the control group. Results. In the whole population, the mean (standard deviation) age was 54.6 (12.9) years, the majority (81.2%) of the participants were overweight or obese, 85.3% had abdominal adiposity, 61.3% were hypertensive, 47.1% had impaired fasting plasma glucose, 8.4% had elevated total cholesterol, 74.8% had low high-density lipoprotein and 10.9% were assessed to be depressed. Ninety-one percent of the whole cohort had at least one metabolic disease. In the breast cancer group, 72.2% had one or more metabolic diseases only (HIV-negative and no evidence of depression), compared with 64.7% of the control group. From a multivariate logistic regression adjusted model, higher household socioeconomic status conferred a 19% reduction in the odds of having advanced-stage breast cancer at diagnosis, while hypertension, dyslipidaemia and HIV were not significantly associated with stage at breast cancer diagnosis in the adjusted model. Conclusions. A large proportion of women experience several comorbidities, highlighting the need to address the chronic noncommunicable disease epidemic in SA and to co-ordinate multidisciplinary primary-, secondary- and tertiary-level care in the country’s complex healthcare system for better outcome.

TPS 711: The exposome, Exhibition Hall, Ground floor, August 26, 2019, 3:00 PM - 4:30 PM Background: The fat accumulation could be due to factor different as genetic, metabolic and environmental. Recently metabolomics was recognized as science that allows us identify metabolic alterations that could increase the BMI. Therefore, the objective of this study is to evaluate the metabolome of amino acids and acylcarnitines according to the body mass index (BMI) in Mexican adolescents. Methods: From a follow-up study in adolescents of 10 and 20 years of age conducted in the Hospital Infantil de México was evaluated in 203 participants the metabolome directed to 40 metabolites related to beta oxidation and gluconeogenesis, which were quantified by tandem mass spectrometry. A factor analysis was performed, identifying three indices (one of the amino acids and two acylcarnitines), which were used to estimate their association with the BMI categories through linear regression models, adjusting for metabolic parameters. The BMI categories were generated using the International Obesity Working Group (IOTF) classification. Results: We observed that the acylcarnitine index score was decreased in adolescents with higher BMI compared with adolescents with normal BMI (overweight β -1.14, p = 0.003, obesity β -1.11, p = 0.004, morbid obesity β -080, p = 0.046). No statistical association was observed between BMI with the rest of indexes. Conclusion: The negative association with the acylcarnitine index with BMI suggests the relationship between the BMI impulse and the preferential use of fatty acids for energy metabolism.

BackgroundThere is increasing evidence that folate, an important component of one-carbon metabolism, modulates the epigenome. Alcohol, which can disrupt folate absorption, is also known to affect the epigenome. We investigated the association of dietary folate and alcohol intake on leukocyte DNA methylation levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Leukocyte genome-wide DNA methylation profiles on approximately 450,000 CpG sites were acquired with Illumina HumanMethylation 450K BeadChip measured among 450 women control participants of a case-control study on breast cancer nested within the EPIC cohort. After data preprocessing using surrogate variable analysis to reduce systematic variation, associations of DNA methylation with dietary folate and alcohol intake, assessed with dietary questionnaires, were investigated using CpG site-specific linear models. Specific regions of the methylome were explored using differentially methylated region (DMR) analysis and fused lasso (FL) regressions. The DMR analysis combined results from the feature-specific analysis for a specific chromosome and using distances between features as weights whereas FL regression combined two penalties to encourage sparsity of single features and the difference between two consecutive features.ResultsAfter correction for multiple testing, intake of dietary folate was not associated with methylation level at any DNA methylation site, while weak associations were observed between alcohol intake and methylation level at CpG sites cg03199996 and cg07382687, with q(val)=0.029 and q(val)=0.048, respectively. Interestingly, the DMR analysis revealed a total of 24 and 90 regions associated with dietary folate and alcohol, respectively. For alcohol intake, 6 of the 15 most significant DMRs were identified through FL.ConclusionsAlcohol intake was associated with methylation levels at two CpG sites. Evidence from DMR and FL analyses indicated that dietary folate and alcohol intake may be associated with genomic regions with tumor suppressor activity such as the GSDMD and HOXA5 genes. These results were in line with the hypothesis that epigenetic mechanisms play a role in the association between folate and alcohol, although further studies are warranted to clarify the importance of these mechanisms in cancer.

Background: Asthma is a common but complex disease with racial/ethnic differences in prevalence, morbidity, and response to therapies. Objective: We sought to perform an analysis of genetic ancestry to identify new loci that contribute to asthma susceptibility. Methods: We leveraged the mixed ancestry of 3902 Latinos and performed an admixture mapping meta-analysis for asthma susceptibility. We replicated associations in an independent study of 3774 Latinos, performed targeted sequencing for fine mapping, and tested for disease correlations with gene expression in the whole blood of more than 500 subjects from 3 racial/ethnic groups. Results: We identified a genome-wide significant admixture mapping peak at 18q21 in Latinos (P = 6.8 x 10(-6)), where Native American ancestry was associated with increased risk of asthma (odds ratio [OR], 1.20; 95% CI, 1.07-1.34; P = .002) and European ancestry was associated with protection (OR, 0.86; 95% CI, 0.77-0.96; P = .008). Our findings were replicated in an independent childhood asthma study in Latinos (P = 5.3 3 10(-3), combined P = 2.6 3 10(-7)). Fine mapping of 18q21 in 1978 Latinos identified a significant association with multiple variants 59 of SMAD family member 2 (SMAD2) in Mexicans, whereas a single rare variant in the same window was the top association in Puerto Ricans. Low versus high SMAD2 blood expression was correlated with case status (13.4% lower expression; OR, 3.93; 95% CI, 2.12-7.28; P <.001). In addition, lower expression of SMAD2 was associated with more frequent exacerbations among Puerto Ricans with asthma. Conclusion: Ancestry at 18q21 was significantly associated with asthma in Latinos and implicated multiple ancestry-informative noncoding variants upstream of SMAD2 with asthma susceptibility. Furthermore, decreased SMAD2 expression in blood was strongly associated with increased asthma risk and increased exacerbations.

There are both limited and conflicting data on the role of dietary fat and specific fatty acids in the development of pancreatic cancer. In this study, we investigated the association between plasma phospholipid fatty acids and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The fatty acid composition was measured by gas chromatography in plasma samples collected at recruitment from375 incident pancreatic cancer cases and375 matched controls. Associations of specific fatty acids with pancreatic cancer risk were evaluated using multivariable conditional logistic regression models with adjustment for established pancreatic cancer risk factors. Statistically significant inverse associations were found between pancreatic cancer incidence and levels of heptadecanoic acid (ORT3‐T1[odds ratio for highest versus lowest tertile] =0.63; 95%CI[confidence interval] = 0.41–0.98; ptrend = 0.036), n‐3 polyunsaturated α‐linolenic acid (ORT3‐T1 = 0.60; 95%CI = 0.39–0.92; ptrend = 0.02) and docosapentaenoic acid (ORT3‐T1 = 0.52; 95%CI = 0.32–0.85; ptrend = 0.008). Industrial trans‐fatty acids were positively associated with pancreatic cancer risk among men (ORT3‐T1 = 3.00; 95%CI = 1.13–7.99; ptrend = 0.029), while conjugated linoleic acids were inversely related to pancreatic cancer among women only (ORT3‐T1 = 0.37; 95%CI = 0.17–0.81; ptrend = 0.008). Among current smokers, the long‐chain n‐6/n‐3 polyunsaturated fatty acids ratio was positively associated with pancreatic cancer risk (ORT3‐T1 = 3.40; 95%CI = 1.39–8.34; ptrend = 0.007). Results were robust to a range of sensitivity analyses. Our findings suggest that higher circulating levels of saturated fatty acids with an odd number of carbon atoms and n‐3 polyunsaturated fatty acids may be related to lower risk of pancreatic cancer. The influence of some fatty acids on the development of pancreatic cancer may be sex‐specific and modulated by smoking.

Background Epidemiological data support a role for fatty acids (FAs) in pancreatic cancer (PC) development, but their effects may differ depending on specific FA class. To date, no study has explored the association between biomarkers of FAs and PC risk within a prospective cohort setting. Methods A case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study was conducted to assess the association between plasma phospholipid FAs and the risk of PC, as well as their interaction with stearoyl-CoA desaturase-1 (SCD-1) polymorphisms. The FA composition was measured by gas chromatography in plasma samples collected at recruitment from 375 PC cases and their matched controls. Multivariable conditional logistic regression models were used to estimate relative risk of PC across tertiles of FAs. Models were adjusted for BMI, total energy intake, height, alcohol intake, history of diabetes mellitus, tobacco smoking status, years of education, and physical activity. Results Statistically significant inverse associations were found between PC incidence and levels of saturated heptadecanoic acid (ORT3-T1[odds ratio for highest versus lowest tertile]=0.63; 95%CI[confidence interval]=0.41‒0.98; Ptrend=0.036), n-3 polyunsaturated α-linolenic acid (ORT3-T1=0.60; 95%CI=0.39‒0.92; Ptrend=0.02) and docosapentaenoic acid (ORT3-T1=0.52; 95%CI=0.32‒0.85; Ptrend=0.008). Among current smokers, the long-chain n-6/n-3 polyunsaturated fatty acid (PUFA) ratio was positively associated with PC risk (ORT3-T1=3.40; 95% CI 1.39-8.34; Ptrend=0.007), while inverse associations emerged for …

Lifestyle and dietary habits in the Mexican population have dramatically changed in the last 20 years, reflected in an increased prevalence of overweight and obesity in both urban and rural adult populations. The prevalence of overweight and obesity in Mexican adults is 38.8% and 32.4%, respectively. In adults, abdominal obesity is more prevalent among women than men (82.8% versus 64.5%, respectively). In women over 60 years of age, overweight and obesity rates are even greater—nearly 40% are overweight and 35.5% obese. A healthy diet has been shown to prevent weight gain. It is therefore important to investigate dietary factors that are most strongly associated with obesity in this highly obese population group. Dietary patterns are used to assess the overall diet. One approach to evaluate dietary patterns is to use a priori patterns which are based on dietary recommendations. The objective of this study was to evaluate the associations between the consumption of food groups and a priori defined dietary patterns and anthropometric measures in women from the CAMA study. Our study population is based on 1062 women (35 to 69-years-old) from the control group of the CAMA study, which is a multi-centre population-based case-control study on breast cancer conducted in Mexico. Each woman was interviewed via personal interview during which dietary intakes were assessed using a semi-quantitative Food Frequency Questionnaire. The indices used in the study are the Dietary Approaches to Stop Hypertension (DASH) score, the Healthy Eating Index (HEI) score, the Mediterranean Diet Score (MDS) and the Diet Quality Index (DQI) score. To estimate associations of food groups and dietary patterns with anthropometric measures, generalized linear regression models were used and adjusted for potential confounders, such as age, centre and educational level. Mean age, body mass index (BMI), waist circumference (WC), hip circumference (HC) and waist-to-hip ratio (WHR) among the participants were 51.1 (years), 30.5 (kg/m2), 99.4 (cm), 109.3 (cm) and 0.91, respectively. When individual food groups were examined, a higher consumption of legumes was associated with lower body mass index (BMI), waist circumference (WC) and hip circumference (HC). Regarding dietary patterns, a higher adherence to MDS was associated with lower WC. We did not observe any significant association between other food groups or a priori dietary patterns and anthropometric measurements in models adjusted for confounders. In this population of Mexican women, most of the a priori dietary scores appeared to be of limited value in predicting the association between diet and anthropometric measures. However, higher adherence to the Mediterranean diet was associated with lower WC.

Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (ORQ4-Q1  = 1.26; 95% CI 1.00-1.58; Ptrend  = 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (ORQ4-Q1  = 1.29; 95% CI 1.02-1.62; Ptrend  = 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation.

BackgroundIntakes of specific fatty acids have been postulated to impact breast cancer risk but epidemiological data based on dietary questionnaires remain conflicting.Materials and methodsWe assessed the association between plasma phospholipid fatty acids and breast cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Sixty fatty acids were measured by gas chromatography in pre-diagnostic plasma phospholipids from 2982 incident breast cancer cases matched to 2982 controls. Conditional logistic regression models were used to estimate relative risk of breast cancer by fatty acid level. The false discovery rate (q values) was computed to control for multiple comparisons. Subgroup analyses were carried out by estrogen receptor (ER) and progesterone receptor expression in the tumours.ResultsA high level of palmitoleic acid [odds ratio (OR) for the highest quartile compared with the lowest OR (Q4-Q1) 1.37; 95% confidence interval (CI), 1.14-1.64; P for trend = 0.0001, q value = 0.004] as well as a high desaturation index (DI16) (16:1n-7/16:0) [OR (Q4-Q1), 1.28; 95% C, 1.07-1.54; P for trend = 0.002, q value = 0.037], as biomarkers of de novo lipogenesis, were significantly associated with increased risk of breast cancer. Levels of industrial trans-fatty acids were positively associated with ER-negative tumours [OR for the highest tertile compared with the lowest (T3-T1)=2.01; 95% CI, 1.03-3.90; P for trend = 0.047], whereas no association was found for ER-positive tumours (P-heterogeneity =0.01). No significant association was found between n-3 polyunsaturated fatty acids and breast cancer risk, overall or by hormonal receptor.ConclusionThese findings suggest that increased de novo lipogenesis, acting through increased synthesis of palmitoleic acid, could be a relevant metabolic pathway for breast tumourigenesis. Dietary trans-fatty acids derived from industrial processes may specifically increase ER-negative breast cancer risk.