-
Andrew Rundle,
John Richie,
Karen Steindorf,
Marco Peluso,
Kim Overvad,
Ole Raaschou-Nielsen,
Francoise Clavel-Chapelon,
Jacob P Linseisen,
Heiner Boeing,
Antonia Trichopoulou, [......],
Antonio Agudo, Goran Berglund,
Bengt Jarvholm,
Sheila Bingham,
Timothy J Key,
Emmanuelle Gormally,
Rodolfo Saracci,
Rudolf Kaaks,
Elio Riboli,
Paolo Vineis
[show abstract]
[hide abstract]
ABSTRACT: The association between physical activity, potential intermediate biomarkers and lung cancer risk was investigated in a study of 230 cases and 648 controls nested within the European Prospective Investigation of Cancer and Nutrition. Data on white blood cell aromatic-DNA adducts by (32)P-post-labelling and glutathione (GSH) in red blood cells were available from a subset of cases and controls. Compared with the first quartile, the fourth quartile of recreational physical activity was associated with a lower lung cancer risk (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.35-0.90), higher GSH levels (+1.87 micromol GSH g(-1) haemoglobin, p = 0.04) but not with the presence of high levels of adducts (OR 1.05, 95% CI 0.38-2.86). Despite being associated with recreational physical activity, in these small-scale pilot analyses GSH levels were not associated with lung cancer risk (OR 0.95, 95% CI 0.84-1.07 per unit increase in GSH levels). Household and occupational activity was not associated with lung cancer risk or biomarker levels.
Biomarkers 02/2010; 15(1):20-30. · 2.21 Impact Factor
-
Ruth C Travis,
Fredrick Schumacher,
Joel N Hirschhorn,
Peter Kraft,
Naomi E Allen,
Demetrius Albanes, Goran Berglund,
Sonja I Berndt,
Heiner Boeing,
H Bas Bueno-de-Mesquita, [......],
Elio Riboli,
Meir Stampfer,
Daniel O Stram,
Michael J Thun,
Anne Tjønneland,
Dimitrios Trichopoulos,
Paolo Vineis,
Jarmo Virtamo,
Loïc Le Marchand,
David J Hunter
[show abstract]
[hide abstract]
ABSTRACT: Sex hormones, particularly the androgens, are important for the growth of the prostate gland and have been implicated in prostate cancer carcinogenesis, yet the determinants of endogenous steroid hormone levels remain poorly understood. Twin studies suggest a heritable component for circulating concentrations of sex hormones, although epidemiologic evidence linking steroid hormone gene variants to prostate cancer is limited. Here we report on findings from a comprehensive study of genetic variation at the CYP19A1 locus in relation to prostate cancer risk and to circulating steroid hormone concentrations in men by the Breast and Prostate Cancer Cohort Consortium (BPC3), a large collaborative prospective study. The BPC3 systematically characterized variation in CYP19A1 by targeted resequencing and dense genotyping; selected haplotype-tagging single nucleotide polymorphisms (htSNP) that efficiently predict common variants in U.S. and European whites, Latinos, Japanese Americans, and Native Hawaiians; and genotyped these htSNPs in 8,166 prostate cancer cases and 9,079 study-, age-, and ethnicity-matched controls. CYP19A1 htSNPs, two common missense variants and common haplotypes were not significantly associated with risk of prostate cancer. However, several htSNPs in linkage disequilibrium blocks 3 and 4 were significantly associated with a 5% to 10% difference in estradiol concentrations in men [association per copy of the two-SNP haplotype rs749292-rs727479 (A-A) versus noncarriers; P = 1 x 10(-5)], and with inverse, although less marked changes, in free testosterone concentrations. These results suggest that although germline variation in CYP19A1 characterized by the htSNPs produces measurable differences in sex hormone concentrations in men, they do not substantially influence risk of prostate cancer.
Cancer Epidemiology Biomarkers & Prevention 10/2009; 18(10):2734-44. · 4.12 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: While conventional pharmacogenetic studies have considered single gene effects, we tested if a genetic score of nine LDL- and HDL-associated single nucleotide polymorphisms, previously shown to predict cardiovascular disease, is related to fluvastatin-induced lipid change. In patients with asymptomatic plaque in the right carotid artery, thus candidates for statin therapy, we related score LDL [APOB(rs693), APOE(rs4420638), HMGCR(rs12654264), LDLR(rs1529729), and PCSK9(rs11591147)] and score HDL [ABCA1(rs3890182), CETP(rs1800775), LIPC(rs1800588), and LPL(rs328)] as well as the combined score LDL+HDL to fluvastatin-induced LDL reduction (+/- metoprolol) (n = 395) and HDL increase (n = 187) following 1 year of fluvastatin treatment. In women, an increasing number of unfavorable alleles (i.e., alleles conferring higher LDL and lower HDL) of score LDL+HDL (P = 0.037) and of score LDL (P = 0.023) was associated with less pronounced fluvastatin-induced LDL reduction. Furthermore, in women, both score LDL+HDL (P = 0.001) and score HDL (P = 0.022) were directly correlated with more pronounced fluvastatin-induced HDL increase, explaining 5.9-11.6% of the variance in treatment response in women. There were no such associations in men. This suggests that a gene score based on variation in nine different LDL- and HDL-associated genes is of importance for the magnitude of fluvastatin HDL increase in women with asymptomatic plaque in the carotid artery.
The Journal of Lipid Research 09/2009; 51(3):625-34. · 5.56 Impact Factor
-
Sekar Kathiresan,
Benjamin F Voight,
Shaun Purcell,
Kiran Musunuru,
Diego Ardissino,
Pier M Mannucci,
Sonia Anand,
James C Engert,
Nilesh J Samani,
Heribert Schunkert, [......],
Nicola Martinelli,
Oliviero Olivieri,
Roberto Corrocher,
Hilma H|[oacute]|lm,
Gudmar Thorleifsson,
Unnur Thorsteinsdottir,
Kari Stefansson,
Ron Do,
Changchun Xie,
David Siscovick
[show abstract]
[hide abstract]
ABSTRACT: We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases and 3,075 controls. We carried out replication in an independent sample with an effective sample size of up to 19,492. SNPs at nine loci reached genome-wide significance: three are newly identified (21q22 near
Nature Genetics 02/2009; 41(3):334-341. · 35.53 Impact Factor
-
Sekar Kathiresan,
Benjamin F Voight,
Shaun Purcell,
Kiran Musunuru,
Diego Ardissino,
Pier M Mannucci,
Sonia Anand,
James C Engert,
Nilesh J Samani,
Heribert Schunkert, [......],
Pascal McKeown,
Erdmann Erdmann,
Inke R König,
Hilma Hólm,
Gudmar Thorleifsson,
Unnur Thorsteinsdottir,
Kari Stefansson,
Ron Do,
Changchun Xie,
David Siscovick
[show abstract]
[hide abstract]
ABSTRACT: We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases and 3,075 controls. We carried out replication in an independent sample with an effective sample size of up to 19,492. SNPs at nine loci reached genome-wide significance: three are newly identified (21q22 near MRPS6-SLC5A3-KCNE2, 6p24 in PHACTR1 and 2q33 in WDR12) and six replicated prior observations (9p21, 1p13 near CELSR2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9). We tested 554 common copy number polymorphisms (>1% allele frequency) and none met the pre-specified threshold for replication (P < 10(-3)). We identified 8,065 rare CNVs but did not detect a greater CNV burden in cases compared to controls, in genes compared to the genome as a whole, or at any individual locus. SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with myocardial infarction risk.
Nature Genetics 02/2009; 41(3):334-41. · 35.53 Impact Factor
-
David Neasham,
Valentina Gallo,
Simonetta Guarrera,
Alison Dunning,
Kim Overvad,
Anne Tjonneland,
Francoise Clavel-Chapelon,
Jakob P Linseisen,
Christian Malaveille,
Pietro Ferrari, [......],
Josè R Quiros, Goran Berglund,
Bengt Jarvholm,
Kay Tee Khaw,
Timothy J Key,
Sheila Bingham,
Tormo M Jose Diaz,
Elio Riboli,
Giuseppe Matullo,
Paolo Vineis
[show abstract]
[hide abstract]
ABSTRACT: We followed-up for mortality and cancer incidence 1088 healthy non-smokers from a population-based study, who were characterized for 22 variants in 16 genes involved in DNA repair pathways. Follow-up was 100% complete. The association between polymorphism and mortality or cancer incidence was analyzed using Cox Proportional Hazard regression models. Ninety-five subjects had died in a median follow-up time of 78 months (inter-quartile range 59-93 months). None of the genotypes was clearly associated with total mortality, except variants for two Double-Strand Break DNA repair genes, XRCC3 18067 C>T (rs#861539) and XRCC2 31479 G>A (rs#3218536). Adjusted hazard ratios were 2.25 (1.32-3.83) for the XRCC3 C/T genotype and 2.04 (1.00-4.13) for the T/T genotype (reference C/C), and 2.12 (1.14-3.97) for the XRCC2 G/A genotype (reference G/G). For total cancer mortality, the adjusted hazard ratios were 3.29 (1.23-7.82) for XRCC3 C/T, 2.84 (0.81-9.90) for XRCC3 T/T and 3.17 (1.21-8.30) for XRCC2 G/A. With combinations of three or more adverse alleles, the adjusted hazard ratio for all cause mortality was 17.29 (95% C.I. 8.13-36.74), and for all incident cancers the HR was 5.28 (95% C.I. 2.17-12.85). Observations from this prospective study suggest that polymorphisms of genes involved in the repair of DNA double-strand breaks significantly influence the risk of cancer and non-cancer disease, and can influence mortality.
DNA Repair 10/2008; 8(1):60-71. · 4.14 Impact Factor
-
Marco Peluso,
Luisa Airoldi,
Armelle Munnia,
Alessandro Colombi,
Fabrizio Veglia,
Herman Autrup,
Alison Dunning,
Seymour Garte,
Emmanuelle Gormally,
Christian Malaveille, [......],
José Ramón Quiros, Goran Berglund,
Bengt Jarvholm,
Nicholas E Day,
Timothy J Key,
Rodolfo Saracci,
Rudolf Kaaks,
Elio Riboli,
Shelia Bingham,
Paolo Vineis
[show abstract]
[hide abstract]
ABSTRACT: In contrast to some extensively examined food mutagens, for example, aflatoxins, N-nitrosamines and heterocyclic amines, some other food contaminants, in particular polycyclic aromatic hydrocarbons (PAH) and other aromatic compounds, have received less attention. Therefore, exploring the relationships between dietary habits and the levels of biomarkers related to exposure to aromatic compounds is highly relevant. We have investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort the association between dietary items (food groups and nutrients) and aromatic DNA adducts and 4-aminobiphenyl-Hb adducts. Both types of adducts are biomarkers of carcinogen exposure and possibly of cancer risk, and were measured, respectively, in leucocytes and erythrocytes of 1086 (DNA adducts) and 190 (Hb adducts) non-smokers. An inverse, statistically significant, association has been found between DNA adduct levels and dietary fibre intake (P = 0.02), vitamin E (P = 0.04) and alcohol (P = 0.03) but not with other nutrients or food groups. Also, an inverse association between fibre and fruit intake, and BMI and 4-aminobiphenyl-Hb adducts (P = 0.03, 0.04, and 0.03 respectively) was observed. After multivariate regression analysis these inverse correlations remained statistically significant, except for the correlation adducts v. fruit intake. The present study suggests that fibre intake in the usual range can modify the level of DNA or Hb aromatic adducts, but such role seems to be quantitatively modest. Fibres could reduce the formation of DNA adducts in different manners, by diluting potential food mutagens and carcinogens in the gastrointestinal tract, by speeding their transit through the colon and by binding carcinogenic substances.
The British journal of nutrition 03/2008; 100(3):489-95. · 3.45 Impact Factor
-
Andrew R Hart,
Robert Luben,
Anja Olsen,
Anne Tjonneland,
Jakob Linseisen,
Gabriele Nagel, Goran Berglund,
Stefan Lindgren,
Olof Grip,
Timothy Key, [......],
Gun Hagglund,
Kim Overvad,
Domenico Palli,
Giovanna Masala,
Elio Riboli,
Hugh Kennedy,
Ailsa Welch,
Kay-Tee Khaw,
Nicholas Day,
Sheila Bingham
[show abstract]
[hide abstract]
ABSTRACT: The causes of ulcerative colitis are unknown, although it is plausible that dietary factors are involved. Case-control studies of diet and ulcerative colitis are subject to recall biases. The aim of this study was to examine the prospective relationship between the intake of nutrients and the development of ulcerative colitis in a cohort study.
The study population was 260,686 men and women aged 20-80 years, participating in a large European prospective cohort study (EPIC). Participants were residents in the UK, Sweden, Denmark, Germany or Italy. Information on diet was supplied and the subjects were followed up for the development of ulcerative colitis. Each incident case was matched with four controls and dietary variables were divided into quartiles.
A total of 139 subjects with incident ulcerative colitis were identified. No dietary associations were detected, apart from a marginally significant positive association with an increasing percentage intake of energy from total polyunsaturated fatty acids (trend across quartiles OR = 1.19 (95% CI = 0.99-1.43) p = 0.07).
No associations between ulcerative colitis and diet were detected, apart from a possible increased risk with a higher total polyunsaturated fatty acid intake. A biological mechanism exists in that polyunsaturated fatty acids are metabolised to pro-inflammatory mediators.
Digestion 02/2008; 77(1):57-64. · 2.05 Impact Factor
-
Steffen Weikert,
Heiner Boeing,
Tobias Pischon,
Cornelia Weikert,
Anja Olsen,
Anne Tjonneland,
Kim Overvad,
Nikolaus Becker,
Jakob Linseisen,
Antonia Trichopoulou, [......],
Aurelio Barricarte,
M J Tormo,
Naomi Allen,
Andrew Roddam,
Sheila Bingham,
Kay-Tee Khaw,
Sabina Rinaldi,
Pietro Ferrari,
Teresa Norat,
Elio Riboli
[show abstract]
[hide abstract]
ABSTRACT: Elevated blood pressure has been implicated as a risk factor for renal cell carcinoma (RCC), but prospective studies were confined to men and did not consider the effect of antihypertensive medication. The authors examined the relation among blood pressure, antihypertensive medication, and RCC in the European Prospective Investigation into Cancer and Nutrition (EPIC). Blood pressure was measured in 296,638 women and men, recruited in eight European countries during 1992-1998, 254,935 of whom provided information on antihypertensive medication. During a mean follow-up of 6.2 years, 250 cases of RCC were identified. Blood pressure was independently associated with risk of RCC. The relative risks for the highest versus the lowest category of systolic (>/=160 mmHg vs. <120 mmHg) and diastolic (>/=100 mmHg vs. <80 mmHg) blood pressures were 2.48 (95% confidence interval: 1.53, 4.02) and 2.34 (95% confidence interval: 1.54, 3.55). Risk estimates did not significantly differ according to sex or use of antihypertensive medication. Individuals taking antihypertensive drugs were not at a significantly increased risk unless blood pressure was poorly controlled. These results support the hypothesis that hypertension, rather than its medications, increases the risk of RCC in both sexes, while effective blood pressure control may lower the risk.
American journal of epidemiology 02/2008; 167(4):438-46. · 5.59 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Little is known about risk factors for acute pancreatitis other than gallstones and alcohol consumption. The aim of this study was to investigate if smoking or body mass index (BMI) are associated with acute pancreatitis and to determine relative risks (RR) for acute pancreatitis related to smoking, BMI, and alcohol consumption.
From 1974 to 1992, selected birth-year cohorts of residents in Malmo, Sweden (born 1921-1949) were invited to a health-screening investigation including physical examination, blood sampling and a questionnaire. In total, 33,346 individuals participated. Cases of acute pancreatitis were identified from diagnosis registries (n = 179). Incidence rates were calculated in different risk factor categories. A Cox's analysis revealed RR.
Current versus never smoking at baseline was associated with acute pancreatitis (RR 2.14, 95% confidence interval (CI) 1.48-3.09) after adjustment for age, sex, BMI and alcohol consumption. This association was stronger in heavy smokers (20-30 cigarettes/day) (RR 3.19, 95% CI 2.03-5.00). Smoking was associated with a RR of 3.57 (95% CI 0.98-13.0) for acute pancreatitis in subjects who reported no alcohol consumption. An increased risk for acute pancreatitis was also found for high versus low risk, self-reported alcohol consumption (RR 2.55, 95% CI 1.59-4.08) and for gamma-GT levels in the highest versus the lowest quartile (RR 2.14, 95% CI 1.32-3.49). There was also a weak correlation between BMI and acute pancreatitis.
Smoking is associated with the incidence of acute pancreatitis in a dose-response manner. and IAP.
Pancreatology 02/2008; 8(1):63-70. · 1.99 Impact Factor
-
David G Cox,
Philip Bretsky,
Peter Kraft,
Paul Pharoah,
Demetrius Albanes,
David Altshuler,
Pilar Amiano, Goran Berglund,
Heiner Boeing,
Julie Buring, [......],
Domenico Palli,
Petra H M Peeters,
Malcolm C Pike,
Elio Riboli,
Daniel O Stram,
Michael Thun,
Anne Tjonneland,
Ruth C Travis,
Dimitrios Trichopoulos,
Meredith Yeager
[show abstract]
[hide abstract]
ABSTRACT: Exposure to exogenous (oral contraceptives, postmenopausal hormone therapy) and endogenous (number of ovulatory cycles, adiposity) steroid hormones is associated with breast cancer risk. Breast cancer risk associated with these exposures could hypothetically be modified by genes in the steroid hormone synthesis, metabolism and signaling pathways. Estrogen receptors are the first step along the path of signaling cell growth and development upon stimulation with estrogens. The National Cancer Institute Breast and Prostate Cancer Cohort Consortium has systematically selected haplotype tagging SNPs in genes along the steroid hormone synthesis, metabolism and binding pathways, including the estrogen receptor beta (ESR2) gene. Four htSNPs tag the 6 major (>5% frequency) haplotypes of the ESR2 gene. These polymorphisms have been genotyped in 5,789 breast cancer cases and 7,761 controls nested within the American Cancer Society Cancer Prevention Study II, European Prospective Investigation into Cancer and Nutrition, Multiethnic Cohort, Nurses' Health Study and Women's Health Study cohorts. None of the SNPs were independently associated with breast cancer risk. One haplotype of the ESR2 gene was associated with breast cancer risk before correction for multiple testing (OR 1.17, 95% CI 1.07-1.28, p = 0.0007). This haplotype remained associated with breast cancer risk after adjustment for multiple testing using a permutation procedure. There was no statistically significant heterogeneity in SNP or haplotype odds ratios across cohorts. These data suggest that inherited variants in ESR2 (while possibly conferring a small increased risk of breast cancer) are not associated with appreciable (OR > 1.2) changes in breast cancer risk among Caucasian women.
International Journal of Cancer 01/2008; 122(2):387-92. · 5.44 Impact Factor
-
Petra H M Peeters,
Nadia Slimani,
Yvonne T van der Schouw,
Philip B Grace,
Carmen Navarro,
Anne Tjonneland,
Anja Olsen,
Francoise Clavel-Chapelon,
Marina Touillaud,
Marie-Christine Boutron-Ruault, [......],
H Bas Bueno-de-Mesquita,
Carla H van Gils,
Guri Skeie,
Paula Jakszyn,
Goran Hallmans, Goran Berglund,
Tim J Key,
Ruth Travis,
Elio Riboli,
Sheila A Bingham
[show abstract]
[hide abstract]
ABSTRACT: Dietary phytoestrogens may play a role in chronic disease occurrence. The aim of our study was to assess the variability of plasma concentrations in European populations. We included 15 geographical regions in 9 European countries (Denmark, France, Germany, Greece, Italy, Spain, Sweden, The Netherlands, and UK) and a 16th region, Oxford, UK, where participants were recruited from among vegans and vegetarians. All subjects were participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma concentrations of 3 isoflavones (daidzein, genistein, and glycitein), 2 metabolites of daidzein [O-desmethylangolensin (O-DMA) and equol] and 2 mammalian lignans (enterodiol and enterolactone) were measured in 1414 participants. We computed geometric means for each region and used multivariate regression analysis to assess the influence of region, adjusted for gender, age, BMI, alcohol intake, smoking status, and laboratory batch. Many subjects had concentrations below the detection limit [0.1 microg/L (0.4 nmol/L)] for glycitein (80%), O-DMA (73%) and equol (62%). Excluding subjects from Oxford, UK, the highest concentrations of isoflavones were in subjects from the Netherlands and Cambridge, UK [2-6 microg/L (7-24 nmol/L); P < 0.05], whereas concentrations for lignans were highest in Denmark [8 microg/L (27 nmol/L); P < 0.05]. Isoflavones varied 8- to 13-fold, whereas lignans varied 4-fold. In the vegetarian/vegan cohort of Oxford, concentrations of isoflavones were 5-50 times higher than in nonvegetarian regions. Region was the most important determinant of plasma concentrations for all 7 phytoestrogens. Despite the fact that plasma concentrations of phytoestrogens in Europe were low compared with Asian populations, they varied substantially among subjects from the 16 different regions.
Journal of Nutrition 05/2007; 137(5):1294-300. · 3.92 Impact Factor
-
Gabriele Nagel,
Jakob Linseisen,
Hendriek C Boshuizen,
Guillem Pera,
Giuseppe Del Giudice,
Gert P Westert,
H Bas Bueno-de-Mesquita,
Naomi E Allen,
Timothy J Key,
Mattijs E Numans, [......],
Antonia Trichopoulou,
Christina Bamia,
Stavroula Soukara,
Jean-Christoph Sabourin,
Fatima Carneiro,
Nadia Slimani,
Mazda Jenab,
Teresa Norat,
Elio Riboli,
Carlos A González
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the association of socioeconomic position with adenocarcinoma of the oesophagus and stomach.
The European Prospective Investigation into Cancer and Nutrition (EPIC) cohort comprises about 520 000 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.
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): 0.43-0.98]. 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.
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.
International Journal of Epidemiology 03/2007; 36(1):66-76. · 6.41 Impact Factor
-
Domenico Palli,
Giovanna Masala,
Giuseppe Del Giudice,
Mario Plebani,
Daniela Basso,
Duccio Berti,
Mattijs E Numans,
Marco Ceroti,
Petra H M Peeters,
H Bas Bueno de Mesquita, [......],
Dimitrios Trichopoulos,
Athina Arvaniti,
Guillem Pera,
Rudolf Kaaks,
Mazda Jenab,
Pietro Ferrari,
Gabriella Nesi,
Fatima Carneiro,
Elio Riboli,
Carlos A Gonzalez
[show abstract]
[hide abstract]
ABSTRACT: Helicobacter pylori (H. pylori), atrophic gastritis, dietary and life-style 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 microg/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% CI 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.
International Journal of Cancer 03/2007; 120(4):859-67. · 5.44 Impact Factor
-
Paolo Vineis,
Gerard Hoek,
Michal Krzyzanowski,
Federica Vigna-Taglianti,
Fabrizio Veglia,
Luisa Airoldi,
Kim Overvad,
Ole Raaschou-Nielsen,
Francoise Clavel-Chapelon,
Jacob Linseisen, [......],
Lluis Cirera,
J Ramon Quiros, Goran Berglund,
Jonas Manjer,
Bertil Forsberg,
Nicholas E Day,
Tim J Key,
Rudolf Kaaks,
Rodolfo Saracci,
Elio Riboli
[show abstract]
[hide abstract]
ABSTRACT: Several countries are discussing new legislation on the ban of smoking in public places, and on the acceptable levels of traffic-related air pollutants. It is therefore useful to estimate the burden of disease associated with indoor and outdoor air pollution.
We have estimated exposure to Environmental Tobacco Smoke (ETS) and to air pollution in never smokers and ex-smokers in a large prospective study in 10 European countries (European Prospective Investigation into Cancer and Nutrition)(N = 520,000). We report estimates of the proportion of lung cancers attributable to ETS and air pollution in this population.
The proportion of lung cancers in never- and ex-smokers attributable to ETS was estimated as between 16 and 24%, mainly due to the contribution of work-related exposure. We have also estimated that 5-7% of lung cancers in European never smokers and ex-smokers are attributable to high levels of air pollution, as expressed by NO2 or proximity to heavy traffic roads. NO2 is the expression of a mixture of combustion (traffic-related) particles and gases, and is also related to power plants and waste incinerator emissions.
We have estimated risks of lung cancer attributable to ETS and traffic-related air pollution in a large prospective study in Europe. Information bias can be ruled out due to the prospective design, and we have thoroughly controlled for potential confounders, including restriction to never smokers and long-term ex-smokers. Concerning traffic-related air pollution, the thresholds for indicators of exposure we have used are rather strict, i.e. they correspond to the high levels of exposure that characterize mainly Southern European countries (levels of NO2 in Denmark and Sweden are closer to 10-20 ug/m3, whereas levels in Italy are around 30 or 40, or higher).Therefore, further reduction in exposure levels below 30 ug/m3 would correspond to additional lung cancer cases prevented, and our estimate of 5-7% is likely to be an underestimate. Overall, our prospective study draws attention to the need for strict legislation concerning the quality of air in Europe.
Environmental Health 02/2007; 6:7. · 2.65 Impact Factor
-
Mazda Jenab,
Joan Sabaté,
Nadia Slimani,
Pietro Ferrari,
Mathieu Mazuir,
Corinne Casagrande,
Genevieve Deharveng,
Anne Tjønneland,
Anja Olsen,
Kim Overvad, [......],
J Ramón Quirós,
Maria Dolores Chirlaque,
Carmen Martinez,
Pilar Amiano, Goran Berglund,
Richard Palmqvist,
Bethany van Guelpen,
Sheila Bingham,
Timothy Key,
Elio Riboli
[show abstract]
[hide abstract]
ABSTRACT: Tree nuts, peanuts and seeds are nutrient dense foods whose intake has been shown to be associated with reduced risk of some chronic diseases. They are regularly consumed in European diets either as whole, in spreads or from hidden sources (e.g. commercial products). However, little is known about their intake profiles or differences in consumption between European countries or geographic regions. The objective of this study was to analyse the population mean intake and average portion sizes in subjects reporting intake of nuts and seeds consumed as whole, derived from hidden sources or from spreads. Data was obtained from standardised 24-hour dietary recalls collected from 36 994 subjects in 10 different countries that are part of the European Prospective Investigation into Cancer and Nutrition (EPIC). Overall, for nuts and seeds consumed as whole, the percentage of subjects reporting intake on the day of the recall was: tree nuts = 4. 4%, peanuts = 2.3 % and seeds = 1.3 %. The data show a clear northern (Sweden: mean intake = 0.15 g/d, average portion size = 15.1 g/d) to southern (Spain: mean intake = 2.99 g/d, average portion size = 34.7 g/d) European gradient of whole tree nut intake. The three most popular tree nuts were walnuts, almonds and hazelnuts, respectively. In general, tree nuts were more widely consumed than peanuts or seeds. In subjects reporting intake, men consumed a significantly higher average portion size of tree nuts (28.5 v. 23.1 g/d, P<0.01) and peanuts (46.1 v. 35.1 g/d, P<0.01) per day than women. These data may be useful in devising research initiatives and health policy strategies based on the intake of this food group.
British Journal Of Nutrition 12/2006; 96 Suppl 2:S12-23. · 3.01 Impact Factor
-
Paolo Vineis,
Gerard Hoek,
Michal Krzyzanowski,
Federica Vigna-Taglianti,
Fabrizio Veglia,
Luisa Airoldi,
Herman Autrup,
Alison Dunning,
Seymour Garte,
Pierre Hainaut, [......],
Aurelio Barricarte,
Lluis Cirera,
J Ramon Quiros, Goran Berglund,
Bertil Forsberg,
Nicholas E Day,
Tim J Key,
Rodolfo Saracci,
Rudolf Kaaks,
Elio Riboli
[show abstract]
[hide abstract]
ABSTRACT: To estimate the relationship between air pollution and lung cancer, a nested case-control study was set up within EPIC (European Prospective Investigation on Cancer and Nutrition). Cases had newly diagnosed lung cancer, accrued after a median follow-up of 7 years among the EPIC ex-smokers (since at least 10 years) and never smokers. Three controls per case were matched. Matching criteria were gender, age (+/-5 years), smoking status, country of recruitment and time elapsed between recruitment and diagnosis. We studied residence in proximity of heavy traffic roads as an indicator of exposure to air pollution. In addition, exposure to air pollutants (NO(2), PM10, SO(2)) was assessed using concentration data from monitoring stations in routine air quality monitoring networks. Cotinine was measured in plasma. We found a nonsignificant association between lung cancer and residence nearby heavy traffic roads (odds ratio = 1.46, 95% confidence interval, CI, 0.89-2.40). Exposure data for single pollutants were available for 197 cases and 556 matched controls. For NO(2) we found an odds ratio of 1.14 (95% CI, 0.78-1.67) for each increment of 10 microg/m(3), and an odds ratio of 1.30 (1.02-1.66) for concentrations greater than 30 microg/m(3). The association with NO(2) did not change after adjustment by cotinine and additional potential confounders, including occupational exposures. No clear association was found with other pollutants.
International Journal of Cancer 08/2006; 119(1):169-74. · 5.44 Impact Factor
-
Heather Spencer Feigelson,
David G Cox,
Howard M Cann,
Sholom Wacholder,
Rudolf Kaaks,
Brian E Henderson,
Demetrius Albanes,
David Altshuler, Goran Berglund,
Franco Berrino, [......],
Carmen Navarro,
Petra H Peeters,
Malcolm C Pike,
Elio Riboli,
V Wendy Setiawan,
Daniel O Stram,
Gilles Thomas,
Michael J Thun,
Anne Tjonneland,
Dimitrios Trichopoulos
[show abstract]
[hide abstract]
ABSTRACT: The 17beta-hydroxysteroid dehydrogenase 1 gene (HSD17B1) encodes 17HSD1, which catalyzes the final step of estradiol biosynthesis. Despite the important role of HSD17B1 in hormone metabolism, few epidemiologic studies of HSD17B1 and breast cancer have been conducted. This study includes 5,370 breast cancer cases and 7,480 matched controls from five large cohorts in the Breast and Prostate Cancer Cohort Consortium. We characterized variation in HSD17B1 by resequencing and dense genotyping a multiethnic sample and identified haplotype-tagging single nucleotide polymorphisms (htSNP) that capture common variation within a 33.3-kb region around HSD17B1. Four htSNPs, including the previously studied SNP rs605059 (S312G), were genotyped to tag five common haplotypes in all cases and controls. Conditional logistic regression was used to estimate odds ratios (OR) for disease. We found no evidence of association between common HSD17B1 haplotypes or htSNPs and overall risk of breast cancer. The OR for each haplotype relative to the most common haplotype ranged from 0.98 to 1.07 (omnibus test for association: X2 = 3.77, P = 0.58, 5 degrees of freedom). When cases were subdivided by estrogen receptor (ER) status, two common haplotypes were associated with ER-negative tumors (test for trend, Ps = 0.0009 and 0.0076; n = 353 cases). HSD17B1 variants that are common in Caucasians are not associated with overall risk of breast cancer; however, there was an association among the subset of ER-negative tumors. Although the probability that these ER-negative findings are false-positive results is high, these findings were consistent across each cohort examined and warrant further study.
Cancer Research 03/2006; 66(4):2468-75. · 7.86 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In this population-based study, risk factors for primary intracerebral hemorrhage (PICH) and PICH subtypes were explored in a nested case-control design.
Risk factors were determined in 22,444 men and 10,902 women (mean age 47 years) who participated in a health-screening programme between 1974 and 1991. 147 subjects with CT or autopsy-verified first-ever PICH during the follow-up period (mean 14 years) were compared with 1,029 stroke-free controls, matched for age, sex and screening-year.
As compared to controls, PICH cases had significantly higher blood pressure (135/91 vs. 127/85 mm Hg), triglycerides (1.7 vs. 1.4 mmol/l), BMI (25.5 vs. 24.8) and shorter stature (1.73 vs. 1.74 m). Diabetes (6.9 vs. 2.8 %) and history of psychiatric morbidity (19.7 vs. 11.0 %) were more common in PICH cases and more of them were living alone (35.4 vs. 25.5%). After adjustment in a backward logistic regression model, high systolic blood pressure, diabetes, high triglycerides, short stature and psychiatric morbidity remained significantly associated with PICH. As compared to the control group, high systolic blood pressure was significantly associated both with nonlobar and lobar PICH. Diabetes and psychiatric morbidity were associated with nonlobar PICH. Smoking doubled the risk for lobar PICH, but was unrelated to nonlobar PICH.
In this prospective population-based study, hypertension, diabetes, height, triglycerides and psychiatric morbidity were risk factors for PICH. Smoking was a risk factor for lobar PICH only.
Cerebrovascular Diseases 02/2006; 21(1-2):18-25. · 2.72 Impact Factor
-
David G Cox,
Hélène Blanché,
Celeste L Pearce,
Eugenia E Calle,
Graham A Colditz,
Malcolm C Pike,
Demetrius Albanes,
Naomi E Allen,
Pilar Amiano, Goran Berglund, [......],
Loic LeMarchand,
Eiliv Lund,
Domenico Palli,
Petra H M Peeters,
Elio Riboli,
Daniel O Stram,
Michael Thun,
Anne Tjonneland,
Dimitrios Trichopoulos,
Meredith Yeager
[show abstract]
[hide abstract]
ABSTRACT: Androgens have been hypothesised to influence risk of breast cancer through several possible mechanisms, including their conversion to estradiol or their binding to the oestrogen receptor and/or androgen receptor (AR) in the breast. Here, we report on the results of a large and comprehensive study of the association between genetic variation in the AR gene and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3).
The underlying genetic variation was determined by first sequencing the coding regions of the AR gene in a panel of 95 advanced breast cancer cases. Second, a dense set of markers from the public database was genotyped in a panel of 349 healthy women. The linkage disequilibrium relationships (blocks) across the gene were then identified, and haplotype-tagging single nucleotide polymorphisms (htSNPs) were selected to capture the common genetic variation across the locus. The htSNPs were then genotyped in the nested breast cancer cases and controls from the Cancer Prevention Study II, European Prospective Investigation into Cancer and Nutrition, Multiethnic Cohort, Nurses' Health Study, and Women's Health Study cohorts (5,603 breast cancer cases and 7,480 controls).
We found no association between any genetic variation (SNP, haplotype, or the exon 1 CAG repeat) in the AR gene and risk of breast cancer, nor were any statistical interactions with known breast cancer risk factors observed.
Among postmenopausal Caucasian women, common variants of the AR gene are not associated with risk of breast cancer.
Breast cancer research: BCR 02/2006; 8(5):R54. · 5.24 Impact Factor
