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| 2. |
- Lumbreras, B., et al.
(author)
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Meat intake and bladder cancer in a prospective study: a role for heterocyclic aromatic amines?
- 2008
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In: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 1573-7225 .- 0957-5243. ; 19:6, s. 649-656
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Journal article (peer-reviewed)abstract
- Objective The suspect carcinogens, heterocyclic amines (HAAs), found in well-done meat require host-mediated metabolic activation before inducing DNA mutations. The role of SULT1A1 and of NAT2 on the activation of HAAs suggests that NAT2 rapid acetylator genotype and SULT1A1 allele variants can have an effect on HAA carcinogenicity. Methods Data were collected as part of a case-control study nested within the EPIC cohort, the Gen Air investigation. EPIC is a prospective study designed to investigate the relationship between nutrition and cancer. Information was collected through a non-dietary questionnaire on lifestyle variables and through a dietary questionnaire. The subjects were restricted to non-smokers. We calculated the matched odds ratio for bladder cancer risk using logistic regression, controlling for potential confounders. Results There were 227 bladder cases and 612 controls matched 1:3. Meat intake and NAT2 genotype were not independently associated with bladder cancer risk. A significant relationship was observed between bladder cancer risk and consumption of meat only among subjects with the rapid NAT2 genotype (odds ratios [OR] 2.9, 95% CI 1.0-7.9 for the 2nd quartile of meat intake; 3.6, 95% CI 1.3-9.7 for the 3rd quartile; and 3.5, 95% CI 1.2-9.7 for the 4th quartile), and was not present among subjects with the slow genotype. An interaction between NAT2 and meat intake was found in logistic regression (P = 0.034). No association was observed for SULT1A *1/2 genotype (1.0; 95% CI 0.7-1.5) and for SULT1A1 *2/2 genotype (0.9; 95% CI 0.5-1.7). Conclusions These results are suggestive of a role of meat intake and NAT2 on bladder cancer risk. They support the hypothesis that among subjects with the rapid NAT2 acetylation genotype higher levels of HAAs exposure are a bladder cancer risk factor. We did not observe an effect of SULT1A1 allele variants on this cancer. The present study adds new information on the possible long-term adverse effects of diets with high meat intake.
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| 3. |
- Manuguerra, M., et al.
(author)
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Multi-factor dimensionality reduction applied to a large prospective investigation on gene-gene and gene-environment interactions
- 2007
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In: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 28:2, s. 414-422
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Journal article (peer-reviewed)abstract
- It is becoming increasingly evident that single-locus effects cannot explain complex multifactorial human diseases like cancer. We applied the multi-factor dimensionality reduction (MDR) method to a large cohort study on gene-environment and gene-gene interactions. The study (case-control nested in the EPIC cohort) was established to investigate molecular changes and genetic susceptibility in relation to air pollution and environmental tobacco smoke (ETS) in non-smokers. We have analyzed 757 controls and 409 cases with bladder cancer (n = 124), lung cancer (n = 116) and myeloid leukemia (n = 169). Thirty-six gene variants (DNA repair and metabolic genes) and three environmental exposure variables (measures of air pollution and ETS at home and at work) were analyzed. Interactions were assessed by prediction error percentage and cross-validation consistency (CVC) frequency. For lung cancer, the best model was given by a significant gene-environment association between the base excision repair (BER) XRCC1-Arg399Gln polymorphism, the double-strand break repair (DSBR) BRCA2-Asn372His polymorphism and the exposure variable 'distance from heavy traffic road', an indirect and robust indicator of air pollution (mean prediction error of 26%, P < 0.001, mean CVC of 6.60, P = 0.02). For bladder cancer, we found a significant 4-loci association between the BER APE1-Asp148Glu polymorphism, the DSBR RAD52-3'-untranslated region (3'-UTR) polymorphism and the metabolic gene polymorphisms COMT-Val158Met and MTHFR-677C > T (mean prediction error of 22%, P < 0.001, mean CVC consistency of 7.40, P < 0.037). For leukemia, a 3-loci model including RAD52-2259C > T, MnSOD-Ala9Val and CYP1A1-Ile462Val had a minimum prediction error of 31% (P < 0.001) and a maximum CVC of 4.40 (P = 0.086). The MDR method seems promising, because it provides a limited number of statistically stable interactions; however, the biological interpretation remains to be understood.
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| 4. |
- Vaissière, Thomas, et al.
(author)
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Quantitative analysis of DNA methylation after whole bisulfitome amplification of a minute amount of DNA from body fluids.
- 2009
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In: Epigenetics : official journal of the DNA Methylation Society. - 1559-2308. ; 4:4, s. 221-30
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Journal article (peer-reviewed)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.
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| 5. |
- Vineis, P., et al.
(author)
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Genetic susceptibility according to three metabolic pathways in cancers of the lung and bladder and in myeloid leukemias in nonsmokers
- 2007
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In: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 18:7, s. 1230-1242
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Journal article (peer-reviewed)abstract
- Background: We chose a set of candidate single nucleotide polymorphisms (SNPs) to investigate gene-environment interactions in three types of cancer that have been related to air pollution (lung, bladder and myeloid leukemia). Patients and methods: The study has been conducted as a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (409 cancer cases and 757 matched controls). We included never and ex-smokers. SNPs were in genes involved in oxidative stress, phase I metabolizing genes, phase 11 metabolizing genes and methylenetetrahydrofolate reductase (MTHFR). Results: The most notable findings are: GSTM1 deletion and bladder cancer risk [odds ratio (OR) = 1.60; 95% confidence interval 1.00-2.56]; CYP1A1 and leukemia (2.22, 1.33-3.70; heterozygotes); CYP1B1 and leukemia (0.47, 0.27-0.84; homozygotes); MnSOD and leukemia (1.91, 1.08-3.38; homozygotes) and NQO1 and lung cancer (8.03, 1.73-37.3; homozygotes). Other statistically significant associations were found in subgroups defined by smoking habits (never or ex-smokers), environmental tobacco smoke or gender, with no obvious pattern. When gene variants were organized according to the three main pathways, the emerging picture was of a strong involvement of combined phase I enzymes in leukemia, with an OR of 5 (1.63-15.4) for those having three or more variant alleles. The association was considerably stronger for leukemias arising before the age of 55.
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| 8. |
- Gonzalez, CA, et al.
(author)
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Smoking and the risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2003
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In: International Journal of Cancer. - : Wiley. - 0020-7136. ; 107:4, s. 629-634
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Journal article (peer-reviewed)abstract
- Smoking has recently been recognised as causally associated with the development of gastric cancer (GC). However, evidence on the effect by sex, duration and intensity of smoking, anatomic subsite and cessation of smoking is limited. Our objective was to assess the relation between tobacco use and GC incidence in the European Prospective Investigation into Cancer and Nutrition (EPIC). We studied data from 521,468 individuals recruited from 10 European countries taking part in the EPIC study. Participants completed lifestyle questionnaires that included questions on lifetime consumption of tobacco and diet in 1991-1998. Participants were followed until September 2002, and during that period 305 cases of stomach cancer were identified. After exclusions, 274 were eligible for the analysis, using the Cox proportional hazard model. After adjustment for educational level, consumption of fresh fruit, vegetables and preserved meat, alcohol intake and body mass index (BMI), there was a significant association between cigarette smoking and gastric cancer risk: the hazard ratio (HR) for ever smokers was 1.45 (95% confidence interval [CI] = 1.08-1.94). The HR of current cigarette smoking was 1.73 (95% CI = 1.06-2.83) in males and 1.87 (95% CI = 1.12-3.12) in females. Hazard ratios increased with intensity and duration of cigarette smoked. A significant decrease of risk was observed after 10 years of quitting smoking. A preliminary analysis of 121 cases with identified anatomic site showed that current cigarette smokers had a higher HR of GC in the cardia (HR = 4.10) than in the distal part of the stomach (HR = 1.94). In this cohort, 17.6 % (95% CI = 10.5-29.5 %) of GC cases may be attributable to smoking. Findings from this large study support the causal relation between smoking and gastric cancer in this European population. Stomach cancer should be added to the burden of diseases caused by smoking. (C) 2003 Wiley-Liss, Inc.
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| 13. |
- Cuttini, M, et al.
(author)
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End-of-life decisions in neonatal intensive care : physicians' selfreported practices in seven European countries
- 2000
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In: The Lancet. - London. - 0140-6736 .- 1474-547X. ; 355:9221, s. 2112-2118
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Journal article (peer-reviewed)abstract
- BackgroundThe ethical issue of foregoing life-sustaining treatment for newborn infants at high risk of death or severe disability is extensively debated, but there is little information on how physicians in different countries actually confront this issue to reach end-of-life decisions. The EURONIC project aimed to investigate practices as reported by physicians themselves.MethodsThe study recruited a large, representative sample of 122 neonatal intensive-care units (NICUs) by census (in Luxembourg, the Netherlands, and Sweden) or stratified random sampling (in France, Germany, the UK, Italy, and Spain) with an overall response rate of 86%. Physicians' practices of end-of-life decision-making were investigated through an anonymous, self-administered questionnaire. 1235 completed questionnaires were returned (response rate 89%).FindingsIn all countries, most physicians reported having been involved at least once in setting limits to intensive care because of incurable conditions (61–96%); smaller proportions reported such involvement because of a baby's poor neurological prognosis (46–90%). Practices such as continuation of current treatment without intensification and withholding of emergency manoeuvres were widespread, but withdrawal of mechanical ventilation was reported by variable proportions (28–90%). Only in France (73%) and the Netherlands (47%) was the administration of drugs with the aim of ending life reported with substantial frequency. Age, length of professional experience, and the importance of religion in the physician's life affected the likelihood of reporting of non-treatment decisions.InterpretationA vast majority of neonatologists in European NICUs have been involved in end-of-life limitation of treatments, but type of decision-making varies among countries. Cultur-related and other country-specific factors are more relevant than characteristics of individual physicians or units in explaining such variability.
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| 15. |
- Riboli, E, et al.
(author)
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European prospective investigation into cancer and nutrition (EPIC): study populations and data collection
- 2002
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In: Public Health Nutrition. - 1475-2727. ; 5:6B, s. 1113-1124
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Journal article (peer-reviewed)abstract
- The European Prospective Investigation into Cancer and. Nutrition (EPIC) is an ongoing multi-centre prospective cohort study designed to investigate the relationship between nutrition and cancer, with the potential for studying other diseases as well. The study currently includes 519 978 participants (366 521 women and 153457 men, mostly aged 35-70 years) in 23 centres located in 10 European countries, to be followed for cancer incidence and cause-specific mortality for several decades. At enrolment, which took place between 1992 and 2000 at each of the different centres, information was collected through a non-dietary questionnaire on lifestyle variables and through a dietary questionnaire addressing usual diet. Anthropometric measurements were performed and blood samples taken, from which plasma, serum, red cells and buffy coat fractions were separated and aliquoted for long-term storage, mostly in liquid nitrogen. To calibrate dietary measurements, a standardised, computer-assisted 24-hour dietary recall was implemented at each centre on stratified random samples of the participants, for a total of 36 900 subjects. EPIC represents the largest single resource available today world-wide for prospective investigations on the aetiology of cancers (and other diseases) that can integrate questionnaire data on lifestyle and diet, biomarkers of diet and of endogenous metabolism (e.g. hormones and growth factors) and genetic polymorphisms. First results of case-control studies nested within the cohort are expected early in 2003. The present paper provides a description of the EPIC study, with the aim of simplifying reference to it in future papers reporting substantive or methodological studies carried out in the EPIC cohort.
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| 16. |
- Slimani, N, et al.
(author)
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European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study: rationale, design and population characteristics
- 2002
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In: Public Health Nutrition. - 1475-2727 .- 1368-9800. ; 5:6B, s. 1125-1145
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Journal article (peer-reviewed)abstract
- The European Prospective Investigation into Cancer and Nutrition (EPIC), which covers a large cohort of half a million men and women from 23 European centres in 10 Western European countries, was designed to study the relationship between diet and the risk of chronic diseases, particularly cancer. Information on usual individual dietary intake was assessed using different validated dietary assessment methods across participating countries. In order to adjust for possible systematic over- or underestimation in dietary intake measurements and correct for attenuation bias in relative risk estimates, a calibration approach was developed. This approach involved an additional dietary assessment common across study populations to re-express individual dietary intakes according to the same reference scale. A single 24-hour diet recall was therefore collected, as the EPIC reference calibration method, from a stratified random sample of 36 900 subjects from the entire EPIC cohort, using a software program (EPIC-SOFT) specifically designed to standardise the dietary measurements across study populations. This paper describes the design and populations of the calibration sub-studies set up in the EPIC centres. In addition, to assess whether the calibration sub-samples were representative of the entire group of EPIC cohorts, a series of subjects' characteristics known possibly to influence dietary intakes was compared in both population groups. This was the first time that calibration sub-studies had been set up in a large multi-centre European study. These studies showed that, despite certain inherent methodological and logistic constraints, a study design such as this one works relatively well in practice. The average response in the calibration study was 78.3% and ranged from 46.5% to 92.5%. The calibration population differed slightly from the overall cohort but the differences were small for most characteristics and centres. The overall results suggest that, after adjustment for age, dietary intakes estimated from calibration samples can reasonably be interpreted as representative of the main cohorts in most of the EPIC centres.
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| 23. |
- Cuttini, M., et al.
(author)
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Should euthanasia be legal? An international survey of neonatal intensive care units staff
- 2004
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In: Archives of Disease in Childhood. - 0003-9888 .- 1468-2044. ; 89:1
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Journal article (peer-reviewed)abstract
- Objective: To present the views of a representative sample of neonatal doctors and nurses in 10 European countries on the moral acceptability of active euthanasia and its legal regulation. Design: A total of 142 neonatal intensive care units were recruited by census (in the Netherlands, Sweden, Hungary, and the Baltic countries) or random sampling (in France, Germany, Italy, Spain, and the United Kingdom), 1391 doctors and 3410 nurses completed an anonymous questionnaire (response rates 89% and 86% respectively). Main outcome measure: The staff opinion that the law in their country should be changed to allow active euthanasia "more than now". Results: Active euthanasia appeared to be both acceptable and practiced in the Netherlands, France, and to a lesser extent Lithuania, and less acceptable in Sweden, Hungary, Italy, and Spain. More then half (53%) of the doctors in the Netherlands, but only a quarter (24%) in France felt that the law should be changed to allow active euthanasia "more than now". For 40% of French doctors, end of life issues should not be regulated by law. Being male, regular involvement in research, less than six years professional experience, and having ever participated in a decision of active euthanasia were positively associated with an opinion favouring relaxation of legal constraints. Having had children, religiousness, and believing in the absolute value of human life showed a negative association. Nurses were slightly more likely to consider active euthanasia acceptable in selected circumstances, and to feel that the law should be changed to allow it more than now. Conclusions: Opinions of health professionals vary widely between countries, and, even where neonatal euthanasia is already practiced, do not uniformly support its legalisation.
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| 25. |
- Elmståhl, S., et al.
(author)
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The Malmö food study : The relative validity of a modified diet history method and an extensive food frequency questionnaire for measuring food intake
- 1996
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In: European Journal of Clinical Nutrition. - 0954-3007. ; 50:3, s. 143-151
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Journal article (peer-reviewed)abstract
- Objective: To assess the relative validity of two diet assessment methods, an extensive quantitative food frequency questionnaire (method A) and a novel shorter quantitative food frequency questionnaire with a 14 day food record (method B). Design: A randomized prospective cohort study. Setting: General community. Subjects: 206 residents of the town of Malmö, aged between 50-69 years, 101 men and 105 women who completed the methods during one year. Methods: Both diet methods were designed to cover the whole diet and portion sizes were estimated using a booklet with 120 photographs; method A comprised 250 items and method B combined a two-week food record measuring lunch and dinner meals and a shorter 130 item quantitative food frequency questionnaire for average consumption of foods, snacks and beverages during the past year. An 18 day dietary record comprising six 3-day weighed records evenly distributed over one year served as a reference method. Results: Pearson's correlation coefficients varied from 0.25 for fat intake to 0.84 for milk products for method A and from 0.32 for fish to 0.88 for meat for method B. Correlations for most food groups ranged between 0.50-0.80, and were higher for method B. Only small changes were noted after adjustment for energy intake. On average for most food groups categorization of subjects into quartiles, 55% of subjects belonging to the lowest quartile, and 57-59% of those belonging to the highest quartile for method A and B were correctly classified. Conclusion: A combined food record with a quantitative food frequency questionnaire is a better tool for food assessment than an extensive food frequency questionnaire. Sponsorship: This study was supported by the Swedish Medical Research Council (K84-19X-7010-01) and the International Agency for Research on Cancer (Collaborative Research Agreement DEB/85/43).
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| 26. |
- Elmståhl, S., et al.
(author)
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The Malmö food study : The reproducibility of a novel diet history method and an extensive food frequency questionnaire
- 1996
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In: European Journal of Clinical Nutrition. - 0954-3007. ; 50:3, s. 134-142
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Journal article (peer-reviewed)abstract
- Objective: To assess the reproducibility of two diet assessment methods, an extensive quantitative food frequency questionnaire (method A) and a novel shorter quantitative food frequency questionnaire with a 14 day food record (method B). Design: A randomized prospective cohort study. Setting: General community. Subjects: 241 residents of the town of Malmö, aged between 50-69 years, 126 men and 115 women who completed the methods one year apart. Methods: Both diet methods were designed to cover the whole diet and portion sizes were estimated using a booklet with 120 photographs; method A comprised 250 items and method B combined a two-week food record measuring lunch and dinner meals and a shorter 130 item quantitative food frequency questionnaire for average consumption of foods, snacks and beverages during the past year; Results: The percent difference between estimated energy intake one year apart were for men 10.7% for method A and 0.2% for method B, corresponding values for women 13.7% and 1.1%. Method B showed a good agreement between measurements for energy-providing nutrients, micronutrients and major food groups, i.e. meat products, edible fats, milk, fish, fruits and vegetables with correlation coefficients between 0.70-0.90 for women. The percent difference of average intake of edible fat was about 10%. Average energy-adjusted Pearson's correlation coefficients were of the order of 0.50-0.80 for most nutrients including 14 fatty acids. The correlation for the ratio between polyunsaturated and saturated fatty acids were about 0.70 for men and 0.80 for women; Conclusion: A modified diet history method combining a food record and a food frequency questionnaire shows good reproducibiiity. Sponsorship: This study was granted by the Swedish Medical research Council (Grant K 84-19X-7010-1) and by the International Agency for Research on cancer (Collaborative research agreement DEB/85/43).
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| 30. |
- Rundle, Andrew, et al.
(author)
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Physical activity and lung cancer among non-smokers : a pilot molecular epidemiological study within EPIC
- 2010
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In: Biomarkers. - : Taylor & Francis. - 1354-750X .- 1366-5804. ; 15:1, s. 20-30
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Journal article (peer-reviewed)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 32P-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 μmol 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.
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