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Sökning: WFRF:(Numans Mattijs E.)

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1.
  • Surendran, Praveen, et al. (författare)
  • Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension
  • 2016
  • Ingår i: Nature Genetics. - Nature Publishing Group. - 1061-4036. ; 48:10, s. 1151-1161
  • Tidskriftsartikel (refereegranskat)abstract
    • High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used -1/4155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.
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2.
  • Palli, D, et al. (författare)
  • CagA+ Helicobacter pylori infection and gastric cancer risk in the EPIC-EURGAST study.
  • 2007
  • Ingår i: International Journal of Cancer. - 0020-7136. ; 120:4, s. 859-67
  • Tidskriftsartikel (refereegranskat)abstract
    • Helicobacter pylori (H. pylori), atrophic gastritis, dietary and lifestyle factors have been associated with gastric cancer (GC). These factors have been evaluated in a large case-control study nested in the European Prospective Investigation into Cancer and Nutrition carried out in 9 countries, including the Mediterranean area. Participants, enrolled in 1992-1998, provided life-style and dietary information and a blood sample (360,000; mean follow-up: 6.1 years). For 233 GC cases diagnosed after enrolment and their 910 controls individually-matched by center, gender, age and blood donation date H. pylori antibodies (antilysate and antiCagA) and plasma Pepsinogen A (PGA) were measured by ELISA methods. Severe chronic atrophic gastritis (SCAG) was defined as PGA circulating levels < 22 mu g/l. Overall, in a conditional logistic regression analysis adjusted for education, smoke, weight and consumption of total vegetables, fruit, red and preserved meat, H. pylori seropositivity was associated with GC risk. Subjects showing only antibodies anti-H. pylori lysate, however, were not at increased risk, while those with antiCagA antibodies had a 3.4-fold increased risk. Overall, the odds ratio associated with SCAG was 3.3 (95% CI 2.2-5.2). According to site, the risk of noncardia GC associated with CagA seropositivity showed a further increase (OR 6.5; 95% CI 3.3-12.6); on the other hand, a ten-fold increased risk of cardia GC was associated with SCAG (OR 11.0; 95% C1 3.0-40.9). These results support the causal relationship between H. pylori CagA+ strains infection, and GC in these European populations even after taking into account dietary habits. This association was limited to distal GC, while serologically defined SCAG was strongly associated with cardia GC, thus suggesting a divergent risk pattern for these 2 sites. (c) 2006 Wiley-Liss, Inc.
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3.
  • Schumann, Gunter, et al. (författare)
  • Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption
  • 2011
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424. ; 108:17, s. 7119-7124
  • Tidskriftsartikel (refereegranskat)abstract
    • Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of similar to 2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene (AUTS2) was associated with alcohol consumption at genome-wide significance (P = 4 x 10(-8) to P = 4 x 10(-9)). We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples (P = 0.026) and significant (P &lt; 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. Downregulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila (P &lt; 0.001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior.
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4.
  • Buckland, Genevieve, et al. (författare)
  • Adherence to a Mediterranean diet and risk of gastric adenocarcinoma within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study
  • 2010
  • Ingår i: American Journal of Clinical Nutrition. - 0002-9165. ; 91:2, s. 381-390
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The Mediterranean dietary pattern is believed to protect against cancer, although evidence from cohort studies that have examined particular cancer sites is limited.OBJECTIVE: We aimed to explore the association between adherence to a relative Mediterranean diet (rMED) and incident gastric adenocarcinoma (GC) within the European Prospective Investigation into Cancer and Nutrition study.DESIGN: The study included 485,044 subjects (144,577 men) aged 35-70 y from 10 European countries. At recruitment, dietary and lifestyle information was collected. An 18-unit rMED score, incorporating 9 key components of the Mediterranean diet, was used to estimate rMED adherence. The association between rMED and GC with respect to anatomic location (cardia and noncardia) and histologic types (diffuse and intestinal) was investigated. A calibration study in a subsample was used to control for dietary measurement error.RESULTS: After a mean follow-up of 8.9 y, 449 validated incident GC cases were identified and used in the analysis. After stratification by center and age and adjustment for recognized cancer risk factors, high compared with low rMED adherence was associated with a significant reduction in GC risk (hazard ratio: 0.67; 95% CI: 0.47, 0.94). A 1-unit increase in the rMED score was associated with a decreased risk of GC of 5% (95% CI: 0.91, 0.99). There was no evidence of heterogeneity between different anatomic locations or histologic types. The calibrated results showed similar trends (overall hazard ratio for GC: 0.93; 95% CI: 0.89, 0.99).CONCLUSION: Greater adherence to an rMED is associated with a significant reduction in the risk of incident GC.
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5.
  • Chajes, Veronique, et al. (författare)
  • Plasma phospholipid fatty acid concentrations and risk of gastric adenocarcinomas in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST)
  • 2011
  • Ingår i: American Journal of Clinical Nutrition. - American Society for Clinical Nutrition. - 1938-3207. ; 94:5, s. 1304-1313
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Epidemiologic data suggest that diet is a risk factor in the etiology of gastric cancer. However, the role of dietary fatty acids, a modifiable risk factor, remains relatively unexplored. Objective: The objective of this study was to determine the association of plasma phospholipid fatty acid concentrations, as biomarkers of exogenous and endogenously derived fatty acids, with the risk of gastric adenocarcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition-Europe Gastric Cancer (EPIC-EURGAST). Design: Fatty acids were measured by gas chromatography in pre-diagnostic plasma phospholipids from 238 cases matched to 626 controls by age, sex, study center, and date of blood donation. Conditional logistic regression models adjusted for Helicobacter pylori infection status, BMI, smoking, physical activity, education, and energy intake were used to estimate relative cancer risks. Results: Positive risk associations for gastric cancer were observed in the highest compared with the lowest quartiles of plasma oleic acid (OR: 1.72; 95% CI: 1.01, 2.94), di-homo-gamma-linolenic acid (OR: 1.92; 95% CI: 1.10, 3.35), alpha-linolenic acid (OR: 3.20; 95% CI: 1.70, 6.06), and the ratio of MUFAs to saturated fatty acids, as an indicator of stearoyl-CoA desaturase-1 enzyme activity (OR: 1.40; 95% CI: 0.81, 2.43). An inverse risk association was observed with the ratio of linoleic to alpha-linolenic acid (OR: 0.37; 95% CI: 0.20, 0.66). Conclusion: These data suggest that a specific prediagnostic plasma phospholipid fatty acid profile, characterized mainly by high concentrations of oleic acid, alpha-linolenic acid, and di-homo-gamma-linolenic acid, which presumably reflect both a complex dietary pattern and altered fatty acid metabolism, may be related to increased gastric cancer risk. Am J Clin Nutr 2011;94:1304-13.
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6.
  • Duell, Eric J., et al. (författare)
  • Genetic variation in alcohol dehydrogenase (ADH1A, ADH1B, ADH1C, ADH7) and aldehyde dehydrogenase (ALDH2), alcohol consumption and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
  • 2012
  • Ingår i: Carcinogenesis. - Oxford University Press. - 0143-3334. ; 33:2, s. 361-367
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies that have examined the association between alcohol consumption and gastric cancer (GC) risk have been inconsistent. We conducted an investigation of 29 genetic variants in alcohol metabolism loci (alcohol dehydrogenase, ADH1 gene cluster: ADH1A, ADH1B and ADH1C; ADH7 and aldehyde dehydrogenase, ALDH2), alcohol intake and GC risk. We analyzed data from a nested case-control study (364 cases and 1272 controls) within the European Prospective Investigation into Cancer and Nutrition cohort. Single nucleotide polymorphisms (SNPs) were genotyped using a customized array. We observed a statistically significant association between a common 3'-flanking SNP near ADH1A (rs1230025) and GC risk [allelic odds ratio (OR)(A v T) = 1.30, 95% confidence interval (CI) = 1.07-1.59]. Two intronic variants, one in ADH1C (rs283411) and one in ALDH2 (rs16941667), also were associated with GC risk (ORT v C = 0.59; 95% CI = 0.38-0.91 and ORT v C = 1.34; 95% CI = 1.00-1.79, respectively). Individuals carrying variant alleles at both ADH1 (rs1230025) and ALDH2 (rs16941667) were twice as likely to develop GC (ORA+T = 2.0; 95% CI = 1.25-3.20) as those not carrying variant alleles. The association between rs1230025 and GC was modified by alcohol intake (< 5 g/day: ORA = 0.89, 95% CI = 0.57-1.39; >= 5 g/day: ORA = 1.45, 95% CI = 1.08-1.94, P-value = 0.05). The association was also modified by ethanol intake from beer. A known functional SNP in ADH1B (rs1229984) was associated with alcohol intake (P-value = 0.04) but not GC risk. Variants in ADH7 were not associated with alcohol intake or GC risk. In conclusion, genetic variants at ADH1 and ALDH2 loci may influence GC risk, and alcohol intake may further modify the effect of ADH1 rs1230025. Additional population-based studies are needed to confirm our results.
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7.
  • Gonzalez, Carlos A, et al. (författare)
  • Fruit and vegetable intake and the risk of stomach and oesophagus adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST).
  • 2006
  • Ingår i: International Journal of Cancer. - 0020-7136. ; 118:10, s. 2559-66
  • Tidskriftsartikel (refereegranskat)abstract
    • It is considered that fruit and vegetable (F&V) protect against oesophagus and gastric cancer (GC). However, 2 recent meta-analyses suggest that the strength of association on GC seems to he weaker for vegetables than for fruit and weaker in cohort than in case-control studies. No evidence exists from cohort studies about adenocarcinoma of oesophagus (ACO). In 521,457 men and women participating in the EPIC cohort in 10 European countries, information of diet and lifestyle was collected at baseline. After an average of 6.5 years of follow-up, a total of 330 GC and 65 ACO, confirmed and classified by a panel of pathologists, was used for the analysis. We examined the relation between F&V intake and GC and ACO. A calibration study in a sub-sample was used to control diet measurement errors. In a sub-sample of cases and a random sample of controls, antibodies against Helicobacter pylori (Hp) were measured and interactions with F&V were examined in a nested case-control study. We observed no association with total vegetable intake or specific groups of vegetables and GC risk, except for the intestinal type, where a negative association is possible regarding total vegetable (calibrated HR 0.66; 95% CI 0.35-1.22 per 100 g increase) and onion and garlic intake (calibrated HR 0.70; 95% CI 0.38-1.29 per 10 g increase). No evidence of association between fresh fruit intake and GC risk was observed. We found a negative but non significant association between citrus fruit intake and the cardia site (calibrated HR 0.77; 95% CI 0.47-1.22 per 100 g increase) while no association was observed with the non-cardia site. Regarding ACO, we found a non significant negative association for vegetable intake and for citrus intake (calibrated HRs 0.72; 95% Cl 0.32-1.64 and 0.77; 95% CI 0.46-1.28 per 100 and 50 g increase, respectively). It seems that lip infection does not modify the effect of F&V intake. Our study supports a possible protective role of vegetable intake in the intestinal type of GC and the ACO. Citrus fruit consumption may have a role in the protection against cardia GC and ACO. (c) 2005 Wiley-Liss, Inc.
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8.
  • Jakszyn, Paula, et al. (författare)
  • Dietary intake of heme iron and risk of gastric cancer in the European prospective investigation into cancer and nutrition study
  • 2012
  • Ingår i: International Journal of Cancer. - John Wiley & Sons. - 0020-7136. ; 130:11, s. 2654-2663
  • Tidskriftsartikel (refereegranskat)abstract
    • Even though recent studies suggest that a high intake of heme iron is associated with several types of cancer, epidemiological studies in relation to gastric cancer (GC) are lacking. Our previous results show a positive association between red and processed meat and non cardia gastric cancer, especially in Helicobacter pylori infected subjects. The aim of the study is to investigate the association between heme iron intake and GC risk in the European prospective investigation into cancer and nutrition (EURGAST-EPIC). Dietary intake was assessed by validated center-specific questionnaires. Heme iron was calculated as a type-specific percentage of the total iron content in meat intake, derived from the literature. Antibodies of H. pylori infection and vitamin C levels were measured in a sub-sample of cases and matched controls included in a nested case-control study within the cohort. The study included 481,419 individuals and 444 incident cases of GC that occurred during an average of 8.7 years of followup. We observed a statistically significant association between heme iron intake and GC risk (HR 1.13 95% CI: 1.011.26 for a doubling of intake) adjusted by sex, age, BMI, education level, tobacco smoking and energy intake. The positive association between heme iron and the risk of GC was statistically significant in subjects with plasma vitamin C <39 mmol/l only (log2 HR 1.54 95% CI (1.012.35). We found a positive association between heme iron intake and gastric cancer risk.
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9.
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10.
  • Nagel, Gabriele, et al. (författare)
  • Socioeconomic positoon and the risk of gastric and overphageal cancer in the European Prospective into Cancer and Nutrition (EPIC-EURGAST)
  • 2007
  • Ingår i: International Journal of Epidemiology. - Oxford University Press. - 1464-3685. ; 36:1, s. 66-76
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives To evaluate the association of socioeconomic position with adenocarcinoma of the oesophagus and stomach. Methods The European Prospective Investigation into Cancer and Nutrition (EPIC) cohort comprises about 520000 participants mostly aged 35-70 years. Information on diet and lifestyle was collected at recruitment. After an average follow-up of 6.5 years, 268 cases with adenocarcinoma of the stomach and 56 of the oesophagus were confirmed. We examined the effect of socioeconomic position on cancer risk by means of educational data and a computed Relative Index of Inequality (RII). In a nested case-control study, adjustment for Helicobacter pylori (H. pylori) infection was performed. Results Higher education was significantly associated with a reduced risk of gastric cancer [vs lowest level of education, hazard ratio (HR): 0.64, 95% Confidence intervals (CI): 0.43-0.981. This effect was more pronounced for cancer of the cardia (HR: 0.42, 95% CI: 0.20-0.89) as compared to non-cardia gastric cancer (HR: 0.66, 95% CI: 0.36-1.22). Additionally, the inverse association of educational level and gastric cancer was stronger for cases with intestinal (extreme categories, HR: 0.13, 95% CI: 0.04-0.44) rather than diffuse histological subtype (extreme categories, HR: 0.71 95% CI: 0.37-1.40). In the nested case-control study, inverse but statistically non-significant associations were found after additional adjustment for H. pylori infection [highest vs lowest level of education: Odds ratio (OR) 0.53, 95% CI: 0.24-1.18]. Educational level was non-significantly, inversely associated with carcinoma of the oesophagus. Conclusion A higher socioeconomic position was associated with a reduced risk of gastric adenocarcinoma, which was strongest for cardia cancer or intestinal histological subtype, suggesting different risk profiles according to educational level. These effects appear to be explained only partially by established risk factors.
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