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ABSTRACT: The association of overweight and obesity with premenopausal breast cancer remained unclear, ethnicity could play a role. A MEDLINE and PUBMED search of all studies on obesity and premenopausal breast cancer published from 2000 to 2010 was conducted. Dose-response meta-analysis was used to determine the risk of premenopausal breast cancer associated with different anthropometric measurements in different ethnic groups. For body mass index (BMI), each 5 kg m(-2) increase was inversely associated with the risk of premenopausal breast cancer (RR = 0.95, 95% confidence interval [CI]: 0.94, 0.97). After stratification by ethnicity, the inverse association remained significant only among Africans (RR = 0.95, 95% CI: 0.91, 0.98) and Caucasians (RR = 0.93, 95% CI: 0.91, 0.95). In contrast, among Asian women, a significant positive association was observed. For waist-to-hip ratio (WHR), each 0.1 unit increase was positively associated with premenopausal breast cancer (RR = 1.08, 95% CI: 1.01, 1.16); the largest effect was detected in Asian women (RR = 1.19, 95% CI: 1.15, 1.24), while small effects of 5% and 6% were observed in African and Caucasian women, respectively. Our results suggest the importance of considering both fat distribution and ethnicity when studying premenopausal breast cancer.
Obesity Reviews 04/2013; · 7.04 Impact Factor
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C Langenberg,
S Sharp,
N G Forouhi,
P W Franks,
M B Schulze,
N Kerrison,
U Ekelund,
I Barroso,
S Panico,
M J Tormo, [......],
B Teucher,
A Tjonneland,
R Tumino,
D L van der A,
W M M Verschuren,
J Tuomilehto,
E Feskens,
M McCarthy,
E Riboli,
N J Wareham
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ABSTRACT: Studying gene-lifestyle interaction may help to identify lifestyle factors that modify genetic susceptibility and uncover genetic loci exerting important subgroup effects. Adequately powered studies with prospective, unbiased, standardised assessment of key behavioural factors for gene-lifestyle studies are lacking. This case-cohort study aims to investigate how genetic and potentially modifiable lifestyle and behavioural factors, particularly diet and physical activity, interact in their influence on the risk of developing type 2 diabetes.
Incident cases of type 2 diabetes occurring in European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts between 1991 and 2007 from eight of the ten EPIC countries were ascertained and verified. Prentice-weighted Cox regression and random-effects meta-analyses were used to investigate differences in diabetes incidence by age and sex.
A total of 12,403 verified incident cases of type 2 diabetes occurred during 3.99 million person-years of follow-up of 340,234 EPIC participants eligible for InterAct. We defined a centre-stratified subcohort of 16,154 individuals for comparative analyses. Individuals with incident diabetes who were randomly selected into the subcohort (n = 778) were included as cases in the analyses. All prevalent diabetes cases were excluded from the study. InterAct cases were followed-up for an average of 6.9 years; 49.7% were men. Mean baseline age and age at diagnosis were 55.6 and 62.5 years, mean BMI and waist circumference values were 29.4 kg/m(2) and 102.7 cm in men, and 30.1 kg/m(2) and 92.8 cm in women, respectively. Risk of type 2 diabetes increased linearly with age, with an overall HR of 1.56 (95% CI 1.48-1.64) for a 10 year age difference, adjusted for sex. A male excess in the risk of incident diabetes was consistently observed across all countries, with a pooled HR of 1.51 (95% CI 1.39-1.64), adjusted for age.
InterAct is a large, well-powered, prospective study that will inform our understanding of the interplay between genes and lifestyle factors on the risk of type 2 diabetes development.
Diabetologia 06/2011; 54(9):2272-82. · 6.81 Impact Factor
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ABSTRACT: SUMMARY: Establishment of large-scale biobanks of human specimens is essential to conduct molecular pathological or epidemiological studies. This requires automation of procedures for specimen cataloguing and tracking through complex analytical processes. The International Agency for Research on Cancer (IARC) develops a large portfolio of studies broadly aimed at cancer prevention and including cohort, case-control and case-only studies in various parts of the world. This diversity of study designs, structure, annotations and specimen collections is extremely difficult to accommodate into a single sample management system (SMS). Current commercial or academic SMS are often restricted to a few sample types and tailored to a limited number of analytic workflows [Voegele et al. (2007) A laboratory information management system (LIMS) for a high throughput genetic platform aimed at candidate gene mutation screening. Bioinformatics, 23, 2504-2506]. Thus, we developed a system based on a three-tier architecture and relying on an Oracle database and an Oracle Forms web application. Data are imported through forms or csv files, and information retrieval is enabled via multi-criteria queries that can generate different types of reports including tables, Excel files, trees, pictures and graphs. The system is easy to install, flexible, expandable and implemented with a high degree of data security and confidentiality. Both the database and the interface have been modeled to be compatible with and adaptable to almost all types of biobanks. Availability and implementation: The SMS source codes, which are under the GNU General Public License, and supplementary data are freely available at 'http://www-gcs.iarc.fr/sms.php' SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Bioinformatics 11/2010; 26(21):2798-800. · 5.47 Impact Factor
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Thomas Vaissière,
Cyrille Cuenin,
Anupam Paliwal,
Paolo Vineis,
G Hoek,
M Krzyzanowski,
L Airoldi,
A Dunning,
S Garte, P Hainaut, [......],
G Berglund,
L Janzon,
B Jarvholm,
N E Day,
T J Key,
R Saracci,
R Kaaks,
E Riboli,
Pierre Hainaut,
Zdenko Herceg
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ABSTRACT: Cell-free circulating DNA isolated from the plasma of individuals with cancer has been shown to harbor cancer-associated changes in DNA methylation, and thus it represents an attractive target for biomarker discovery. However, the reliable detection of DNA methylation changes in body fluids has proven to be technically challenging. Here we describe a novel combination of methods that allows quantitative and sensitive detection of DNA methylation in minute amounts of DNA present in body fluids (quantitative Methylation Analysis of Minute DNA amounts after whole Bisulfitome Amplification, qMAMBA). This method involves genome-wide amplification of bisulphite-modified DNA template followed by quantitative methylation detection using pyrosequencing and allows analysis of multiple genes from a small amount of starting DNA. To validate our method we used qMAMBA assays for four genes and LINE1 repetitive sequences combined with plasma DNA samples as a model system. qMAMBA offered high efficacy in the analysis of methylation levels and patterns in plasma samples with extremely small amounts of DNA and low concentrations of methylated alleles. Therefore, qMAMBA will facilitate methylation studies aiming to discover epigenetic biomarkers, and should prove particularly valuable in profiling a large sample series of body fluids from molecular epidemiology studies as well as in tracking disease in early diagnostics.
Epigenetics: official journal of the DNA Methylation Society 06/2009; 4(4):221-30. · 4.58 Impact Factor
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M Peluso, P Hainaut,
L Airoldi,
H Autrup,
A Dunning,
S Garte,
E Gormally,
C Malaveille,
G Matullo,
A Munnia,
E Riboli,
P Vineis
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ABSTRACT: Several large prospective investigations are under way or are planned in different parts of the world, aiming at the investigation of gene-environment interactions for chronic diseases. Technical, practical and ethical issues are raised by such large investigations. Here we describe how such issues were approached within a case-control study nested in EPIC, a large European cohort, and the kind of validation studies that have been set up. The GenAir investigation aimed at measuring the effects of air pollution and environmental tobacco smoke on human health in EPIC with a nested design and with biological measures. Validation studies included (a) comparisons between cotinine measurements, hemoglobin adducts and questionnaire data; (b) an analysis of the determinants of DNA adduct concentration; (c) comparison among different genotyping methods; (d) an analysis of the determinants of plasma DNA amounts. We also describe how the ethical issues were dealt with in our investigation.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 08/2005; 574(1-2):92-104. · 2.85 Impact Factor
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ABSTRACT: The tumour suppressor protein p53 mediates cell-cycle arrest, DNA repair and apoptosis after activation by multiple forms of cellular stresses. When activated, this "master protein" modulates its response depending on the type and intensity of the stress. The TP53 gene with its nearly 20,000 described mutations is the most mutated gene in cancer. Most mutations are missense and occur at over 200 codons within the central portion of the gene. In several cancers, the distribution of mutation types and sites follow a specific pattern reflecting the effects of environmental mutagens. An example for such a "mutagen fingerprint" is TP53 mutation at codon 249 in hepatocellular carcinoma in regions of the world characterised by high levels of the mutagen aflatoxin B1 and endemic HBV infection. Recently, TP53 mutations have been detected in surrogate sources of genetic material such as free circulating DNA isolated from plasma. Plasma TP53 mutations can be detected in the blood of pre-cancer and cancer patients, with potential application for early cancer detection. Thus, TP53 mutations have multiple applications as markers of mutagenic exposures, or as intermediate end-points in assessment of cancer occurrence and progression.
Revue d Épidémiologie et de Santé Publique 07/2005; 53(3):257-66. · 0.78 Impact Factor
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P Vineis,
L Airoldi,
F Veglia,
L Olgiati,
R Pastorelli,
H Autrup,
A Dunning,
S Garte,
E Gormally, P Hainaut, [......],
V Krogh,
D Palli,
S Panico,
R Tumino,
B Bueno-De-Mesquita,
P Peeters,
G Berglund,
G Hallmans,
R Saracci,
E Riboli
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ABSTRACT: To investigate the association between environmental tobacco smoke, plasma cotinine concentration, and respiratory cancer or death.
Nested case-control study within the European prospective investigation into cancer and nutrition (EPIC).
303,020 people from the EPIC cohort (total 500,000) who had never smoked or who had stopped smoking for at least 10 years, 123,479 of whom provided information on exposure to environmental tobacco smoke. Cases were people who developed respiratory cancers or died from respiratory conditions. Controls were matched for sex, age (plus or minus 5 years), smoking status, country of recruitment, and time elapsed since recruitment.
Newly diagnosed cancer of lung, pharynx, and larynx; deaths from chronic obstructive pulmonary disease or emphysema. Plasma cotinine concentration was measured in 1574 people.
Over seven years of follow up, 97 people had newly diagnosed lung cancer, 20 had upper respiratory cancers (pharynx, larynx), and 14 died from chronic obstructive pulmonary disease or emphysema. In the whole cohort exposure to environmental tobacco smoke was associated with increased risks (hazard ratio 1.30, 95% confidence interval 0.87 to 1.95, for all respiratory diseases; 1.34, 0.85 to 2.13, for lung cancer alone). Higher results were found in the nested case-control study (odds ratio 1.70, 1.02 to 2.82, for respiratory diseases; 1.76, 0.96 to 3.23, for lung cancer alone). Odds ratios were consistently higher in former smokers than in those who had never smoked; the association was limited to exposure related to work. Cotinine concentration was clearly associated with self reported exposure (3.30, 2.07 to 5.23, for detectable/non-detectable cotinine), but it was not associated with the risk of respiratory diseases or lung cancer. Frequent exposure to environmental tobacco smoke during childhood was associated with lung cancer in adulthood (hazard ratio 3.63, 1.19 to 11.11, for daily exposure for many hours).
This large prospective study, in which the smoking status was supported by cotinine measurements, confirms that environmental tobacco smoke is a risk factor for lung cancer and other respiratory diseases, particularly in ex-smokers.
BMJ (Clinical research ed.). 03/2005; 330(7486):277.
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M. Jenab,
H.B. Bueno-de-Mesquita,
P Ferrari,
F.J.B van Duijnhoven,
T. Norat,
T. Pischon,
E.H. Helvoirt-Jansen,
N. Slimani,
G.B. Byrnes,
S Rinaldi, [......],
M. Dorronsoro,
C.A. Gonzalez,
G Hallmans,
R Palmqvist,
A. Roddam,
T.J. Key,
K T Khaw,
P Autier, P Hainaut,
E Riboli
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E Gormally,
P Vineis,
G Matullo,
F Veglia,
E. Caboux,
E Le Roux,
M Peluso,
S Garte,
S Guarrera,
A Munnia, [......],
A. Barricarte,
C Navarro,
J.R. Quiros,
G Hallmans,
N E Day,
T.J. Key,
R Saracci,
R. Kaaks,
E Riboli, P Hainaut
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P Vineis,
G. Hoek,
M Krzyzanowski,
F. Vigna-Taglianti,
F Veglia,
L Airoldi,
H Autrup,
A Dunning,
S Garte, P Hainaut, [......],
A. Barricarte,
L. Cirera,
J.R. Quiros,
G Berglund,
B Forsberg,
N E Day,
T.J. Key,
R Saracci,
R. Kaaks,
E Riboli
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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.
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M Peluso,
A Munnia,
G. Hoek,
M Krzyzanowski,
F Veglia,
L Airoldi,
H Autrup,
A Dunning,
S Garte, P Hainaut, [......],
J.R. Quirós,
G Berglund,
L Janzon,
B. Jarvholm,
N E Day,
T.J. Key,
R Saracci,
R. Kaaks,
E Riboli,
P Vineis
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ABSTRACT: Objectives were to investigate prospectively the ability of DNA adducts to predict cancer and to study the determinants of adducts, especially air pollutants. DNA adducts were measured in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) investigation. Cases included newly diagnosed lung cancer (n = 115), upper respiratory cancers (pharynx and larynx; n = 82), bladder cancer (n = 124), leukemia (n = 166), and chronic obstructive pulmonary disease or emphysema deaths (n = 77) accrued after a median follow-up of 7 years among the EPIC former smokers and never-smokers. Three controls per case were matched for questionnaire analyses and two controls per case for laboratory analyses. Matching criteria were gender, age, smoking status, country of recruitment, and follow-up time. Individual exposure to air pollution was assessed using concentration data from monitoring stations in routine air quality monitoring networks. Leukocyte DNA adducts were analyzed blindly using ³²P postlabeling technique. Adducts were associated with the subsequent risk of lung cancer, with an odds ratio (OR) of 1.86 [95% confidence interval (95% CI), 0.88-3.93] when comparing detectable versus nondetectable adducts. The association with lung cancer was stronger in never-smokers (OR, 4.04; 95% CI, 1.06-15.42) and among the younger age groups. After exclusion of the cancers occurring in the first 36 months of follow-up, the OR was 4.16 (95% CI, 1.24-13.88). A positive association was found between DNA adducts and ozone (O₃) concentration. Our prospective study suggests that leukocyte DNA adducts may predict lung cancer risk of never-smokers. Besides, the association of DNA adduct levels with O₃ indicates a possible role for photochemical smog in determining DNA damage.
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L Airoldi,
P Vineis,
A Colombi,
L Olgiati,
C. Osta,
R Fanelli,
L. Manzi,
F Veglia,
H Autrup,
A Dunning, [......],
M.D. Chirlaque,
J.R. Quirós,
G Berglund,
B. Jarvholm,
G Hallmans,
N E Day,
N Allen,
R Saracci,
R. Kaaks,
E Riboli
[show abstract]
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ABSTRACT: The aim of this study was to evaluate whether biomarkers of environmental tobacco smoke exposure [i.e., 4-aminobiphenylhemoglobin (4-ABP-Hb) adducts] were predictive of the risk of tobacco-related cancers and diseases. We did a casecontrol study nested within the European Prospective Investigation into Cancer and Nutrition, involving 190 controls and 149 cases (incident cancer of the lung, bladder, pharynx, larynx, oral cavity, leukemias, and chronic obstructive pulmonary disease or emphysema deaths). All individuals were never smokers or ex smokers for >10 years. 4-ABP-Hb adducts were analyzed in peripheral blood collected before the onset of the disease (median, 7 years). Overall, 4-ABP-Hb adducts were higher, although not statistically significantly so, in cases (as a whole) than controls. In the control population, high fruit and vegetable consumption significantly lowered the frequency of detectable adducts (Fisher’s exact test, P = 0.025). Restricting the analysis to women, 4-ABP-Hb adducts were higher in cases than controls (Mann-Whitney P = 0.036) and the odds ratio (OR) for the presence/absence of adducts was 2.42 [95% confidence interval (95% CI), 1.18-4.98]. Moreover, the association of adducts with the individual cancer types was stronger in women than in the whole study population, although statistically significant only for leukemias (OR, 2.77; 95% CI, 1.06-7.20). The results provide some evidence that women may be more susceptible to environmental tobacco smoke, as suggested by their higher adduct levels. The most important finding of this prospective study is that, at least in women, 4-ABP-Hb adducts may help identify subjects at high risk of cancers related to environmental tobacco smoke exposure.
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E Gormally, P Hainaut,
E. Caboux,
L Airoldi,
H Autrup,
C Malaveille,
A Dunning,
S Garte,
G Matullo,
K. Overvad, [......],
G Hallmans,
N E Day,
T.J. Key,
F Veglia,
M Peluso,
T. Norat,
R Saracci,
R. Kaaks,
E Riboli,
P Vineis
