33 results on '"Seymour Garte"'
Search Results
2. DNA adducts and lung cancer risk: a prospective study
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H. Bas Bueno-de-Mesquita, Herman Autrup, Heiner Boeing, Paolo Vineis, Armelle Munnia, Aurelio Barricarte, Ole Raaschou-Nielsen, Seymour Garte, Carlos González, Fabrizio Veglia, Petra H.M. Peeters, Carmen Martinez, Carmen Navarro, J. Ramón Quirós, Elio Riboli, Antonia Trichopoulou, Emmanuelle Gormally, Merethe Kumle, Göran Berglund, Dimitrios Trichopoulos, Salvatore Panico, Timothy J. Key, Lars Janzon, Vittorio Krogh, Kim Overvad, Luisa Airoldi, Rudolf Kaaks, Michal Krzyzanowski, Pierre Hainaut, Giuseppe Matullo, Bengt Järvholm, Marco Peluso, Alison M. Dunning, Gerard Hoek, Rosario Tumino, Françoise Clavel-Chapelon, Anna Kaladidi, Christian Malaveille, Nicholas E. Day, Domenico Palli, J. Linseisen, Rodolfo Saracci, Miren Dorronsoro, Peluso, M, Munnia, A, Hoek, G, Krzyzanowski, M, Veglia, F, Airoldi, L, Autrup, H, Dunning, A, Garte, S, Hainaut, P, Malaveille, C, Gormally, E, Matullo, G, Overvad, K, RAASCHOU NIELSEN, O, CLAVEL CHAPELON, F, Linseisen, J, Boeing, H, Trichopoulou, A, Trichopoulos, D, Kaladidi, A, Palli, D, Krogh, V, Tumino, R, Panico, Salvatore, BUENO DE MESQUITA, Hb, Peeters, Ph, Kumle, M, Gonzalez, Ca, Martinez, C, Dorronsoro, M, Barricarte, A, Navarro, C, Quiros, Jr, Berglund, G, Janzon, L, Jarvholm, B, Day, Ne, Key, Tj, Saracci, R, Kaaks, R, Riboli, E, Vineis, P., and Faculteit Diergeneeskunde
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Adult ,Male ,pharynx ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Gastroenterology ,lung ,DNA Adducts ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Risk Factors ,Internal medicine ,DNA adduct ,medicine ,Humans ,air pollutants ,ddc:610 ,Prospective Studies ,Risk factor ,Prospective cohort study ,Lung cancer ,Aged ,030304 developmental biology ,larynx ,0303 health sciences ,business.industry ,Respiratory disease ,Cancer ,Odds ratio ,Middle Aged ,Diergeneeskunde (DGNK) ,medicine.disease ,3. Good health ,European Prospective Investigation into Cancer and Nutrition ,Dna adducts ,bladder cancer ,Oncology ,13. Climate action ,Case-Control Studies ,030220 oncology & carcinogenesis ,Immunology ,Female ,business - 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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- 2016
3. Meat intake and bladder cancer in a prospective study: a role for heterocyclic aromatic amines?
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Elio Riboli, Hb B. Bueno-De-Mesquita, Françoise Clavel-Chapelon, Rudolf Kaaks, R. Saracci, Seymour Garte, M-D Chirlaque, Tj J. Key, Paolo Boffetta, Jp P. Linseisen, Anne Tjønneland, Göran Hallmans, Antonia Trichopoulou, Vittorio Krogh, Göran Berglund, Carlos Martinez, J. R. Quirós, C. A. Gonzalez, Heiner Boeing, Eiliv Lund, Christian Malaveille, Pamela Ferrari, Domenico Palli, Paolo Vineis, M. Dorronsoro, Salvatore Panico, Ne E. Day, Blanca Lumbreras, Marco Peluso, Rosario Tumino, Kim Overvad, P. H. Peeters, Teresa Norat, Aurelio Barricarte, Lumbreras, B, Garte, S, Overvad, K, Tjonneland, A, Clavel Chapelon, F, Linseisen, Jp, Boeing, H, Trichopoulou, A, Palli, D, Peluso, M, Krogh, V, Tumino, R, Panico, Salvatore, Bueno De Mesquita, Hb, Peeters, Ph, Lund, E, Martinez, C, Dorronsoro, M, Barricarte, A, Chirlaque, Md, Quiros, Jr, Berglund, G, Hallmans, G, Day, Ne, Key, Tj, Saracci, R, Kaaks, R, Malaveille, C, Ferrari, P, Boffetta, P, Norat, T, Riboli, E, Gonzalez, Ca, Vineis, P., and University of Groningen
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Cancer Research ,Meat ,Genotype ,Arylamine N-Acetyltransferase ,Colorectal cancer ,meat intake ,N-acetyltransferase ,COLORECTAL-CANCER ,DIET ,Odds Ratio ,medicine ,Humans ,BREAST-CANCER ,Genetic Predisposition to Disease ,ddc:610 ,Allele ,Prospective cohort study ,Carcinogen ,RISK ,Bladder cancer ,business.industry ,COLON-CANCER ,Case-control study ,food and beverages ,CONSUMPTION ,Feeding Behavior ,medicine.disease ,GENE-ENVIRONMENT INTERACTIONS ,gene-environment interaction ,N-ACETYLATION ,Urinary Bladder Neoplasms ,Oncology ,PROSPECTIVE COHORT ,Case-Control Studies ,Cancer research ,bladder cancer ,NUTRITION ,Food Habits ,business - Abstract
Background: 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. © 2008 Springer Science+Business Media B.V.
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- 2016
4. Role of simian virus 40 in cancer incidence in solid organ transplant patients
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V. Paracchini, A. Nanni Costa, Emanuela Taioli, and Seymour Garte
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Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,models of viral transmission ,Population ,Simian virus 40 ,Biology ,medicine.disease_cause ,Virus ,Organ transplantation ,Risk Factors ,Internal medicine ,Neoplasms ,Epidemiology ,medicine ,cohort study ,Humans ,Organ donation ,education ,Aged ,education.field_of_study ,Incidence (epidemiology) ,Incidence ,Cancer ,Genetics and Genomics ,Organ Transplantation ,Middle Aged ,medicine.disease ,Tissue Donors ,Immunology ,DNA, Viral ,epidemiology ,Female ,Carcinogenesis - Abstract
Transplant recipients have an increased risk of developing cancer in comparison with the general population. We present here data on cancer development in transplanted subjects who received organs from donors whose DNA was previously examined for the genomic insertion of Simian Virus 40 (SV40). Active follow-up of 387 recipients of solid organs donated by 134 donors, not clinically affected by cancer, was performed through the National Transplant Center (NTC). The average length of follow-up after transplant was 671+/-219 days (range 0-1085 days). Out of 134 proposed donors, 120 were utilised for organ donation. Of these, 12 (10%) were classified as positive for SV40 genomic insertion. None of the 41 recipients of organs from SV40 positive donors developed a tumour during the follow-up. In all, 11 recipients of organs given by SV40 negative donors developed a tumour (cancer incidence: 0.015 per year). In conclusion, cancer rates observed in our study are comparable to what reported by the literature in transplanted patients. Recipients of solid organs from SV40 positive donors do not have an increased risk of cancer after transplant. The role of SV40 in carcinogenesis in transplanted patients may be minimal.
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- 2006
5. Genetic Susceptibility to Cancer
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Seymour Garte and Seymour Garte
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- Oncology, Veterinary medicine, Medical genetics, Epidemiology, Public health
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Despite recent progress in many areas of treatment and control, cancer remains a frightening threat to everyone. While scientists have known for decades that the majority of human cancers are caused by environmental agents such as radiation and the chemicals in cigarette smoke, not everyone who smokes gets lung cancer. Furthermore, many people who assiduously avoid all possible risk from smoking, diet, and pollution still succumb to some form of cancer later in life. Does this mean that there is an element of blind chance in the underlying mechanisms of human carcinogenesis? To what extent do genetic influences play a role in determining the cancer risk of individuals? A number of `cancer families', in which several closely related individuals have suffered from various specific forms of cancer, have been studied by genetic epidemiologists. However, for the majority of cancer cases, little or no discernible genetic influence or family history is found. Recent research has discovered that for many of these `sporadic'(non-familial) cancer cases, defects or aberrations in certain metabolic genes not previously associated with genetic cancer risk may contribute to either causing the disease or at least increasing the chances of developing cancer. It is therefore possible that much of what has previously passed for `bad luck'may turn out to be a new type of `bad genes'. Genetic Susceptibility to Cancer explains that this new idea of `bad genes'may contain an unexpected positive side. The carcinogenic effects of these metabolic genes, unlike those of the oncogenes and tumor suppressor genes that are responsible for the inherited cancer syndromes, can potentially be overcome or nullified. Genetic Susceptibility to Cancer will provide a valuable reference for health professionals, researchers, clinicians and biomedical scientists who are interested in the current thinking in this critically important areaof cancer management.
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- 2013
6. Models of interaction between metabolic genes and environmental exposure in cancer susceptibility
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Emanuela Taioli, Carlo Zocchetti, and Seymour Garte
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Lung Neoplasms ,Health, Toxicology and Mutagenesis ,Alpha (ethology) ,Biology ,Logistic regression ,Models, Biological ,Polymorphism (computer science) ,Neoplasms ,Genetic predisposition ,Cytochrome P-450 CYP1A1 ,Humans ,Gene–environment interaction ,Amino Acids ,Carcinogen ,Genetics ,Polymorphism, Genetic ,Smoking ,Public Health, Environmental and Occupational Health ,Case-control study ,Environmental exposure ,Environmental Exposure ,Metabolism ,Case-Control Studies ,Regression Analysis ,Algorithms ,Research Article - Abstract
Polymorphic metabolic genes that confer enhanced genetic susceptibility to the carcinogenic effects of certain environmental carcinogens act according to a type 2 interaction between genetic and environmental risk factors. This type of interaction, for which the gene has no effect on disease outcome by itself but only modifies the risk associated with exposure, must be treated differently from other types of gene-environment interaction. We present a method to analyze different dose effects often seen in studies involving these genes. We define a low exposure-gene effect, when a greater degree of gene environment interaction appears at lower doses of exposure (the interaction follows an inverse dose function), and a converse high exposure-gene effect, when the interaction increases as a function of dose. Using a standard logistic regression model, we define a new term, alpha, that can be determined asa function of exposure dose in order to analyze epidemiological studies for the type of exposure-gene effect. These models are illustrated by the use of hypothetical case-control data as well as examples from the literature. Images Figure 1
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- 1998
7. Relationship between ambient air pollution and DNA damage in Polish mothers and newborns
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Greg Cosma, David K. Manchester, T. L. Young, Alicja Gladek-Yarborough, Robin M. Whyatt, Seymour Garte, Thomas B. Cooper, Mary C. Randall, Douglas A. Bell, Frederica P. Perera, Regina M. Santella, Ruth Ottman, and Wieslaw Jedrychowski
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Adult ,Genotype ,Health, Toxicology and Mutagenesis ,Matched-Pair Analysis ,Physiology ,Enzyme-Linked Immunosorbent Assay ,Biology ,Polymerase Chain Reaction ,Toxicology ,DNA Adducts ,Pregnancy ,medicine ,Cytochrome P-450 CYP1A1 ,Humans ,Polycyclic Aromatic Hydrocarbons ,Carcinogen ,Glutathione Transferase ,Retrospective Studies ,Biologic marker ,Fetus ,Air Pollutants ,Smoking ,Public Health, Environmental and Occupational Health ,Infant, Newborn ,Urban Health ,Transplacental ,Environmental exposure ,Environmental Exposure ,medicine.disease ,Maternal Exposure ,Prenatal Exposure Delayed Effects ,Linear Models ,Female ,Poland ,Restriction fragment length polymorphism ,Biomarkers ,Polymorphism, Restriction Fragment Length ,Research Article ,DNA Damage - Abstract
Industrialized regions in Poland are characterized by high ambient pollution, including polycyclic aromatic hydrocarbons (PAHs) from coal burning for industry and home heating. In experimental bioassays, certain PAHs are transplacental carcinogens and developmental toxicants. Biologic markers can facilitate evaluation of effects of environmental PAHs on the developing infant. We measured the amount of PAHs bound to DNA (PAH-DNA adducts) in maternal and umbilical white blood cells. The cohort consisted of 70 mothers and newborns from Krakow, Poland, an industrialized city with elevated air pollution. Modulation of adduct levels by genotypes previously linked to risk of lung cancer, specifically glutathione S-transferase MI (GSTM1) and cytochrome P4501A1 (CYP1A1) Msp restriction fragment length polymorphism (RFLP), was also investigated. There was a dose-related increase in maternal and newborn adduct levels with ambient pollution at the women's place of residence among subjects who were not employed away from home (p < or = 0.05). Maternal smoking (active and passive) significantly increased maternal (p < or = 0.01) but not newborn adduct levels. Neither CYP1A1 Msp nor GSTM1 polymorphisms was associated with maternal adducts. However, adducts were significantly higher in newborns heterozygous or homozygous for the CYP1A1 Msp RFLP compared to newborns without the RFLP (p = 0.04). Results indicate that PAH-induced DNA damage in mothers and newborns is increased by ambient air pollution. In the fetus, this damage appears to be enhanced by the CYP1A1 Mspl polymorphism. Images Figure 1
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- 1998
8. Pooled analysis of studies on DNA adducts and dietary vitamins
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Ivan Kalina, Camille Ragin, Domenico Palli, Emanuela Taioli, Peter B. Farmer, Giuseppe Matullo, Fulvio Ricceri, Antonio Agudo, Seymour Garte, Radim J. Sram, Paolo Vineis, Carlos A. Gonzales, Todor A. Popov, Aerie Minor, and Marco Peluso
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Vitamin ,Health, Toxicology and Mutagenesis ,medicine.medical_treatment ,Population ,Physiology ,Article ,Antioxidants ,03 medical and health sciences ,chemistry.chemical_compound ,DNA Adducts ,0302 clinical medicine ,DNA adduct ,Genetics ,Medicine ,Humans ,education ,030304 developmental biology ,0303 health sciences ,education.field_of_study ,Cancer prevention ,Carcinogenicity ,business.industry ,Vitamin E ,Confounding ,Smoking ,Antioxidant vitamins ,Age Factors ,Environmental exposure ,Vitamins ,Environmental Exposure ,Ascorbic acid ,Polycyclic aromatic hydrocarbons ,3. Good health ,Diet ,Biomarkers ,Molecular epidemiology ,Biochemistry ,chemistry ,030220 oncology & carcinogenesis ,Carcinogens ,business - Abstract
OBJECTIVES: There is some evidence that dietary components that are rich in antioxidant and vitamins are inversely associated with DNA adduct levels induced by environmental carcinogens such as polycyclic aromatic hydrocarbons, although the epidemiologic data are inconsistent. This study addresses the association between vitamins, DNA adducts and smoking. METHODS: A combined analysis of individual data on the association between bulky DNA adducts and dietary vitamins was conducted. A Medline search was performed to identify studies on healthy subjects in which smoking and vitamins intake information were available, and bulky DNA adducts were measured in peripheral blood with 32P-postlabelling. Eight published studies met the eligibility criteria, and individual data from 7 data sets including 2758 subjects were obtained. GSTM1 and GSTT1 were also available on all the subjects. RESULTS: Vitamin E was inversely significantly associated with DNA adducts after adjustment for possible confounding factors. Vitamins A and C were not independent predictors of DNA adducts. A stratified analysis showed that vitamin A had a significant inverse association with DNA adducts in ever smokers only. CONCLUSIONS: This result is relevant to planning any future chemo-preventive interventions directed to high risk subgroups of the population, for cancer prevention. This study was partially supported by grants from ‘‘Associazione Italiana per la Ricerca sul Cancro’’, and by the Environmental Cancer Risk, Nutrition and Individual Susceptibility European Union Network of Excellence (ECNIS, Contract No. FOOD-CT-2005- 513943) and a grant from NIH 5P20CA132385-03.
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- 2010
9. Recurrence in oral and pharyngeal cancer is associated with quantitative MGMT promoter methylation
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Robert W. Sobol, Jiangying Chen, Scott M. Langevin, Susanne M. Gollin, Xiao-hong Wang, Seymour Garte, Emanuela Taioli, Ashley R. Brown, and Camille Ragin
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Male ,Cancer Research ,Survival ,DNA repair ,Population ,Biology ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,Surgical oncology ,CDKN2A ,Recurrence ,Genetics ,medicine ,Humans ,education ,Promoter Regions, Genetic ,DNA Modification Methylases ,neoplasms ,Cyclin-Dependent Kinase Inhibitor p16 ,030304 developmental biology ,Aged ,0303 health sciences ,education.field_of_study ,Tumor Suppressor Proteins ,HPV infection ,Pharyngeal Neoplasms ,Methylation ,DNA Methylation ,Middle Aged ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,digestive system diseases ,3. Good health ,DNA Repair Enzymes ,Oncology ,030220 oncology & carcinogenesis ,DNA methylation ,Cancer research ,Biomarker (medicine) ,Female ,Mouth Neoplasms ,Research Article - Abstract
Background Biomarkers that predict clinical response, tumor recurrence or patient survival are severely lacking for most cancers, particularly for oral and pharyngeal cancer. This study examines whether gene-promoter methylation of tumor DNA correlates with survival and recurrence rates in a population of patients with oral or pharyngeal cancer. Methods The promoter methylation status of the DNA repair gene MGMT and the tumor suppressor genes CDKN2A and RASSF1 were evaluated by methylation-specific PCR in 88 primary oral and pharyngeal tumors and correlated with survival and tumor recurrence. Quantitative MGMT methylation was also assessed. Results 29.6% of the tumors presented with MGMT methylation, 11.5% with CDKN2A methylation and 12.1% with RASSF1 methylation. MGMT promoter methylation was significantly associated with poorer overall and disease-free survival. No differences in methylation status of MGMT and RASSF1 with HPV infection, smoking or drinking habits were observed. A significant inverse trend with the amount of MGMT methylation and overall and disease-free survival was observed (ptrend = 0.002 and 0.001 respectively). Conclusion These results implicate MGMT promoter methylation as a possible biomarker for oral and pharyngeal cancer prognosis. The critical role of MGMT in DNA repair suggests that defective DNA repair may be correlative in the observed association between MGMT promoter methylation and tumor recurrence. Follow-up studies should include further quantitative MSP-PCR measurement, global methylation profiling and detailed analysis of downstream DNA repair genes regulated by promoter methylation.
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- 2009
10. Bulky DNA adducts, 4-aminobiphenyl-haemoglobin adducts and diet in the European Prospective Investigation into Cancer and Nutrition (EPIC) prospective study
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Carmen Martinez, Petra H.M. Peeters, Merethe Kumle, Paolo Vineis, Armelle Munnia, Seymour Garte, Bas Bueno-de-Mesquita, Emmanuelle Gormally, Ole Raaschou-Nielsen, Antonio Agudo, Giuseppe Matullo, Bengt Järvholm, Françoise Clavel-Chapelon, José Ramón Quirós, Göran Berglund, Marco Peluso, Alison M. Dunning, Rosario Tumino, Alessandro Colombi, Salvatore Panico, Timothy J. Key, Luisa Airoldi, Elio Riboli, S Bingham, Fabrizio Veglia, Rudolf Kaaks, Antonia Trichopoulou, Aurelio Barricarte, Vittorio Krogh, Christian Malaveille, Nicholas E. Day, Kim Overvad, Rodolfo Saracci, Herman Autrup, María José Tormo, Domenico Palli, J. Linseisen, Heiner Boeing, Miren Dorronsoro, Faculteit Medische Wetenschappen/UMCG, Peluso, M, Airoldi, L, Munnia, A, Colombi, A, Veglia, F, Autrup, H, Dunning, A, Garte, S, Gormally, E, Malaveille, C, Matullo, G, Overvad, K, Raaschou Nielsen, O, Clavel Chapelon, F, Linseisen, J, Boeing, H, Trichopoulou, A, Palli, D, Krogh, V, Tumino, R, Panico, Salvatore, Bueno De Mesquita, Bh, Peeters, Ph, Kumle, M, Agudo, A, Martinez, C, Dorronsoro, M, Barricarte, A, Tormo, Mj, Quiros, Jr, Berglund, G, Jarvholm, B, Day, Ne, Key, Tj, Saracci, R, Kaaks, R, Riboli, E, Bingham, S, Vineis, P., [Peluso,M, Munnia, A] Cancer Risk Factor Branch, Analytical and Biomolecular Cytology Unit, CSPO-Scientific Institute of Tuscany, Florence, Italy. [Airoldi,L, Colombi,A] Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. [Veglia, F, Matullo,G] ISI Foundation, Turin, Italy. [Autrup,H] Department of Environmental and Occupational Medicine, Aarhus, Denmark. [Dunning, A] Department of Oncology, University of Cambridge, Cambridge, UK. [Garte,S] Genetics Research Institute, Milan, Italy. [Gormally,E, Malaveille,C] International Agency for Research on Cancer, Lyon, France. [Overhad,K] Department of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark. [Raaschou-Nielsen,O] Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. [Clavel-Chapelon,F] INSERM (Institut National de la Sante´ et de la Recherche Me´dicale), ERI 20, EA 4045, and Institut Gustave Roussy, Villejuif, F-94805, France. [Linseisen,J] Division of Clinical Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, German. [Boeing,H] German Institute of Human Nutrition, Potsdam-Rehbu¨cke, Germany. [Trichopoulou,A] Department of Hygiene and Epidemiology, Medical School, University of Athens, Athens, Greece. [Palli,D] Molecular and Nutritional Epidemiology Unit, CSPO-Scientific Institute of Cancer Prevention Tuscany Region, Florence, Italy. [Krogh,V] Department of Epidemiology, National Cancer Institute, Milan, Italy. [Tumino,R] Cancer Registry, Azienda Ospedaliera ‘Civile MP Arezzo’, Ragusa, Ital. [Panico,S] Dipartimento di Medicina Clinica e Sperimentale, Universita` Federico II, Naples, Italy. [Bueno-De-Mesquita,BH] Centre for Nutrition and Health, National Institute for Public Health and the Environment, Bilthoven, The Netherland. [Peeters,PH] Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands. [Kumle,M] Institute of Community Medicine, University of Tromso, Tromso, Norway. [Agudo,A] Department of Epidemiology, Catalan Institute of Oncology, Barcelona, Spain. [Martinez,C] Andalusian School of Public Health, Granada, Spain. [Dorronsoro,M] Department of Public Health of Guipuzkoa, San Sebastian, Spain. [Barricarte,A] Public Health Institute, Navarra, Spain. [Tormo,MJ] Epidemiology Department, Murcia Health Council, Murcia, Spain. Quiros, JR] Direccio´n General de Salud Pu´blica, Consejerı´a de Salud y Servicios Sanitarios Asturias, Oviedo, Spain. [Berglund,G] Malmo¨ Diet and Cancer Study, Lund University, Malmo¨, Sweden. [Jarvholm,G] Department of Nutritional Research, University of Umea˚, Umea˚ , Sweden. [Day,ND, Bingham,S] MRC Dunn Human Nutrition Unit, Cambridge University, UK. [Key,TJ].Cancer Research UK Epidemiology Unit, University of Oxford, Oxford, UK. [Saracci,R] IFC National Research Council, Pisa, Italy. [Kaas,R] Division of Epidemiology, DKFZ Heidelberg, Germany. [Riboli,E] Imperial College London, London, UK. [Vineis,P] University of Turin, Turin, Italy. Department of Epidemiology and Public Health, Imperial College of Science, Technology and Medicine, Norfolk Place, London W2 1PG, UK, This paper was made possible by a grant of the European Community (5th Framework Programme) to P. V. (grant QLK4–CT–1999–00 927) and a grant of the Compagnia di San Paolo to the ISI Foundation. All authors are independent from funders. Mortality data for the Netherlands were obtained from Statistics Netherlands. Also, the work described in the paper was carried out with the financial support of: Europe Against Cancer Program of the European Commission (SANCO), ISCIII, Red de Centros RCESP, C03/09, Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, German Federal Ministry of Education and Research, Danish Cancer Society, Health Research Fund (FIS) of the Spanish Ministry of Health, Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, Cancer Research UK, Medical Research Council, UK, Stroke Association, UK, British Heart Foundation, Department of Health, UK, Food Standards Agency, UK, Wellcome Trust, UK, Greek Ministry of Health, Greek Ministry of Education, Italian Association for Research on Cancer (AIRC), Italian National Research Council, Dutch Ministry of Public Health, Welfare and Sports, World Cancer Research Fund, Swedish Cancer Society, Swedish Scientific Council, Regional Government of Ska°ne, Sweden, Norwegian Cancer Society, and Research Council of Norway.
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Dietary Fiber ,Male ,Aflatoxin ,Erythrocytes ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Hemoglobins [Medical Subject Headings] ,medicine.medical_treatment ,air pollution ,RESISTANT STARCH ,Medicine (miscellaneous) ,GUIDELINES ,Carcinógenos ,Body Mass Index ,COLORECTAL-CANCER ,Food group ,chemistry.chemical_compound ,Hemoglobins ,Vegetables ,Chemicals and Drugs::Chemical Actions and Uses::Toxic Actions::Environmental Pollutants::Air Pollutants [Medical Subject Headings] ,Leukocytes ,Aductos de ADN ,Nutritional Physiological Phenomena ,Food science ,Prospective Studies ,RISK ,DNA adducts ,Haemoglobin adducts ,Non-smokers ,Fibre intake ,Air pollution ,Publication Characteristics::Study Characteristics::Multicenter Study [Medical Subject Headings] ,Air Pollutants ,Nutrition and Dietetics ,Chemistry ,Technology, Industry, Agriculture::Food and Beverages::Food::Dietary Fiber [Medical Subject Headings] ,Chemicals and Drugs::Chemical Actions and Uses::Toxic Actions::Noxae::Carcinogens [Medical Subject Headings] ,COLON-CANCER ,Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA Damage::DNA Adducts [Medical Subject Headings] ,Fabaceae ,Middle Aged ,fibre intake ,European Prospective Investigation into Cancer and Nutrition ,Europe ,Biochemistry ,4-Aminobiphenyl ,Colonic Neoplasms ,Hemoglobinas ,Female ,SMOKERS ,Alcohol Drinking ,BLADDER-CANCER ,European Prospective Investigation into Cancer and Nutrition (EPIC) ,haemoglobin adducts ,non-smokers ,RATS ,POLYCYCLIC AROMATIC-HYDROCARBONS ,Ozone ,LUNG-CANCER ,DNA adduct ,medicine ,Humans ,Contaminantes del aire ,ddc:610 ,Carcinogen ,Aged ,Estudio multicéntrico ,Vitamin E ,Fruit ,Multivariate Analysis ,Fibras en la dieta ,Carcinogens ,Biomarkers ,Food contaminant - Abstract
Udgivelsesdato: 2008-Feb-14 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.
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- 2008
11. Evidence of gene gene interactions in lung carcinogenesis in a large pooled analysis
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Riccardo Puntoni, Simone Benhamou, Sisko Anttila, Monica Spinola, Paolo Vineis, Richard C. Strange, Seymour Garte, Agneta Rannug, Ari Hirvonen, Emanuela Taioli, and Chikako Kiyohara
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Oncology ,Male ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Variation (Genetics) ,medicine.disease_cause ,Tobacco smoke ,Gene interaction ,Reference Values ,Risk Factors ,Internal medicine ,Genetic variation ,medicine ,Genetic predisposition ,Confidence Intervals ,Cytochrome P-450 CYP1A1 ,Odds Ratio ,Humans ,Genetic Predisposition to Disease ,Lung cancer ,Glutathione Transferase ,business.industry ,Smoking ,Cancer ,Genetic Variation ,General Medicine ,Odds ratio ,respiratory system ,medicine.disease ,Immunology ,Female ,business ,Carcinogenesis - Abstract
To test the hypothesis of interaction among genetic variants in increasing the individual risk of cancer, we have studied the cumulative effect on lung cancer risk of variants in three metabolic genes, CYP1A1, GSTM1 and GSTT1, which are involved in the metabolism of the tobacco smoke constituents and environmental contaminants, polycyclic aromatic hydrocarbons and of other lung carcinogens. We have selected from the Genetic Susceptibility to Environmental Carcinogens pooled analysis all the studies on lung cancer conducted after 1991 in which all variants were available. The data set includes 611 cases and 870 controls. We found a cumulative effect of the combination of the a priori 'at-risk' alleles for these genes (P for trend 0.004). The risk of lung cancer was increased with the combination of CYP1A1*2B or CYP1A1*4 alleles and the double deletion of both GSTM1 and GSTT1 up to an odds ratio (OR) of 8.25 (95% confidence interval 2.29-29.77) for the combination including CYP1A1*4; among never smokers, the latter combination was associated with an OR of 16.19 (1.90-137). Estimates did not change after adjustment by the number of cigarettes smoked and duration of smoking were consistent across ethnicities and were approximately the same for adenocarcinomas and squamous cell carcinomas. These observations from a large pooled analysis strongly suggest the existence of gene-gene interactions in lung carcinogenesis. People with rare combinations of common gene variants have a high risk of cancer and can be assimilated to subjects with highly penetrant mutations. This study has been made possible by a grant of the Compagnia di San Paolo to the ISI Foundation, Torino, by a grant from the European Commission to E.T. (CAN/96/33919), by a grant from the Associazione and Fondazione Italiana Ricerca Cancro (AIRC and FIRC), and to the Environmental Cancer Risk, Nutrition, Individual Suscriptibility (ECNIS) Network of Excellence (grant FOOD-CT-2005-513943) (WP8) and NIH P50CA090440-07.
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- 2007
12. Genetic susceptibility according to three metabolic pathways in cancers of the lung and bladder and in myeloid leukemias in nonsmokers
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Rudolf Kaaks, H. B. Bueno-De-Mesquita, Fabrizio Veglia, M. Dorronsoro, R. Tumino, Marco Peluso, Alison M. Dunning, Herman Autrup, Elio Riboli, Kim Overvad, Christian Malaveille, Nicholas E. Day, J. R. Quirós, Aurelio Barricarte, Giuseppe Matullo, Bengt Järvholm, Paolo Crosignani, F. Clavel-Chapelon, Paolo Vineis, R. Saracci, Domenico Palli, C. Navarro, Timothy J. Key, J. Linseisen, Luisa Airoldi, Carlos Martinez, Göran Berglund, C. A. Gonzalez, Heiner Boeing, Eiliv Lund, Salvatore Panico, Seymour Garte, Antonia Trichopoulou, P. H. Peeters, Ole Raaschou-Nielsen, Vineis, P, Veglia, F, Garte, S, Malaveille, C, Matullo, G, Dunning, A, Peluso, M, Airoldi, L, Overvad, K, RAASCHOU NIELSEN, O, CLAVEL CHAPELON, F, Linseisen, J, Kaaks, R, Boeing, H, Trichopoulou, A, Palli, D, Crosignani, P, Tumino, R, Panico, Salvatore, BUENO DE MESQUITA, H, Peeters, P, Lund, E, Gonzalez, C, Martinez, C, Dorronsoro, M, Barricarte, A, Navarro, C, Quiros, J, Berglund, G, Jarvholm, B, Day, N, Key, T, Saracci, R, Riboli, E, and Autrup, H.
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Oncology ,metabolic genes ,Male ,medicine.medical_specialty ,Lung Neoplasms ,Arylamine N-Acetyltransferase ,Polymorphism, Single Nucleotide ,Internal medicine ,medicine ,Genetic predisposition ,Cytochrome P-450 CYP1A1 ,Humans ,Genetic Predisposition to Disease ,ddc:610 ,Lung cancer ,Methylenetetrahydrofolate Reductase (NADPH2) ,Glutathione Transferase ,Bladder cancer ,biology ,business.industry ,Smoking ,leukemia ,Myeloid leukemia ,Cancer ,Hematology ,Middle Aged ,medicine.disease ,bladder cancer ,lung cancer ,nonsmokers ,European Prospective Investigation into Cancer and Nutrition ,Isoenzymes ,Leukemia ,Oxidative Stress ,Endocrinology ,Urinary Bladder Neoplasms ,Leukemia, Myeloid ,Methylenetetrahydrofolate reductase ,Case-Control Studies ,Cytochrome P-450 CYP1B1 ,biology.protein ,Female ,Aryl Hydrocarbon Hydroxylases ,Sulfotransferases ,business ,Metabolic Networks and Pathways - 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 II 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. Mortality data for The Netherlands were obtained from ‘Statistics Netherlands’. This paper was made possible by a grant of the European Community (5th Framework Programme) to PV (grant QLK4CT199900927) and a grant of the Compagnia di San Paolo to the ISI Foundation, and a grant of the EC to the ECNIS Network of Excellence (grant FOOD-CT-2005-513943)(WP4-8). All authors are independent from funders. Also, the work described in the paper was carried out with the financial support of: Europe Against Cancer Program of the European Commission (SANCO); ISCIII, Red de Centros RCESP, C03/09; Deutsche Krebshilfe; Deutsches Krebsforschungszentrum; German Federal Ministry of Education and Research; Danish Cancer Society; Health Research Fund (FIS) of the Spanish Ministry of Health; Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra; Cancer Research, UK; Medical Research Council, UK; Stroke Association, UK; British Heart Foundation; Department of Health, UK; Food Standards Agency, UK; Wellcome Trust, UK; Greek Ministry of Education; Italian Association for Research on Cancer; Italian National Research Council; Dutch Ministry of Public Health, Welfare and Sports; World Cancer Research Fund; Swedish Cancer Society; Swedish Scientific Council; Regional Government of Skåne, Sweden; Norwegian Cancer Society.
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- 2007
13. Role of GSTT1 deletion in DNA oxidative damage by exposure to polycyclic aromatic hydrocarbons in humans
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Emanuela Taioli, Seymour Garte, Peter B. Farmer, Radim J. Sram, Todor A. Popov, and Ivan Kalina
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Genetics ,Cancer Research ,Biology ,medicine.disease_cause ,Isozyme ,susceptibility ,Oxidative Stress ,Oncology ,Biochemistry ,GSTT1 Gene ,Genotype ,Environmental Carcinogenesis ,Genetic variation ,medicine ,cohort study ,Humans ,Polycyclic Compounds ,Gene ,Oxidative stress ,Carcinogen ,biological markers ,DNA Damage ,Glutathione Transferase - Abstract
A useful approach for studies on the mechanisms of genetic variation in cancer susceptibility is to use intermediary biochemical endpoints with mechanistic relevance to the genes under study. We examined the effects of individual genotype at seven metabolic gene loci on a marker of oxidative DNA damage, 8-oxo-7,8-dihydro-2-deoxyguanosine, in people exposed to polycyclic aromatic hydrocarbons (PAH) from three Central European cities. The GSTT1 homozygous deletion variant was associated with a significant protective effect for exposure to total PAHs and to eight specific PAHs, although the magnitude and significance of the effect varied among these compounds. Categorical sensitivity analysis was used to determine that the frequency of the GSTT1 deletion was significantly higher in people who proved to be more resistant to the DNA damaging effects of PAH exposure than in people who were the most sensitive. There is a growing literature on the protective effect of GSTT1 deletion in both disease and intermediary endpoints related to environmental carcinogenesis. The mechanism for this effect might be related to specific PAH substrate specificities, or could be related to other functions of GSTT1 gene in oxidative stress induced damage pathways. Grant sponsor: European Commission (Quality of life and management of living resources program); Grant number: QLK4-CT-2000-00091; Grant sponsor: ECNIS project; Grant number: EU Contract 513943.
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- 2007
14. Metabolic genotypes as modulators of asbestos-related pleural malignant mesothelioma risk: a comparison of Finnish and Italian populations
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Monica Neri, Paola Marroni, Riccardo Puntoni, Giovanni Paolo Ivaldi, Rosangela Filiberti, Emanuela Taioli, Seymour Garte, Ari Hirvonen, Pier Aldo Canessa, and Anna Verna
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Oncology ,Mesothelioma ,Pathology ,medicine.medical_specialty ,glutathione S-transferase M1 ,Genotype ,Arylamine N-Acetyltransferase ,Pleural Neoplasms ,Population ,medicine.disease_cause ,Asbestos ,N-acetyltransferase 2 ,Pleural disease ,Internal medicine ,Occupational Exposure ,medicine ,Odds Ratio ,Humans ,Genetic Predisposition to Disease ,Pleural Neoplasm ,Risk factor ,education ,Malignant mesothelioma ,Finland ,Glutathione Transferase ,Epoxide Hydrolases ,education.field_of_study ,GSTT1 ,business.industry ,Public Health, Environmental and Occupational Health ,Case-control study ,Cancer ,medicine.disease ,NAT2 ,EPHX1 ,Italy ,Case-Control Studies ,microsomal epoxide hydrolase ,glutathione S-transferase T1 ,business ,GSTM1 - Abstract
The role of CYP1A1, GSTM1, GSTT1, EPHX1, and NAT2 genotypes in susceptibility to malignant mesothelioma (MM) was compared in two case-control studies, previously conducted in two countries where different types of asbestos fibers have been used [Hirvonen et al., 1995. Inherited GSTM1 and NAT2 defects as concurrent risk modifiers in asbestos-related human malignant mesothelioma. Cancer Res. 55, 2981-2983; Hirvonen et al., 1996. Glutathione S-Transferase and N-Acetyltransferase genotypes and asbestos-associated pulmonary disorders. J. Natl. Cancer Inst.88, 1853-1856; Neri et al., 2005. Pleural malignant mesothelioma, genetic susceptibility and asbestos exposure. Mutat. Res. 592, 36-44]. Fifty-seven asbestos-exposed MM patients and 255 controls were recruited in Italy, 48 cases and 121 controls in Finland. In order to make the two studies comparable, they have been updated and new genotyping analyses have been performed. The NAT2 fast acetylator and EPHX1 low-activity genotypes were positively associated with MM in the Italian study, while they were negatively associated with this malignancy in the Finnish one. A combined significant effect was also observed in the Italian study for the NAT2 fast acetylator and EPHX1 low-activity genotypes, while this combination was protective in the Finnish study. Combination of NAT2 fast acetylator and GSTM1 null genotype posed a significantly increased risk of MM in the Italian, but not in the Finnish study. The opposite results obtained in Finland and Italy may be ascribed to random chance, but a role may be hypothesized for the fact that different types of asbestos have been used in the two countries. This work was supported by the EU funded ECNIS network of excellence, by the Italian Ministry of Health and by “Fondazione ONLUS-Buzzi”. The work of MN was partially supported by AIRC (Italian Association for Cancer Research).
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- 2006
15. Air pollution and risk of lung cancer in a prospective study in Europe
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Rudolf Kaaks, H. Bas Bueno-de-Mesquita, Domenico Palli, Kim Overvad, Giuseppe Matullo, J. Linseisen, Antonia Trichopoulou, Seymour Garte, Pierre Hainaut, Eiliv Lund, Petra H.M. Peeters, Rodolfo Saracci, Aurelio Barricarte, J. Ramón Quirós, Lluís Cirera, Carmen Martinez, Heiner Boeing, Elio Riboli, Federica Vigna-Taglianti, Michal Krzyzanowski, Françoise Clavel-Chapelon, Göran Berglund, Ole Raaschou-Nielsen, Timothy J. Key, Luisa Airoldi, Salvatore Panico, Miren Dorronsoro, Christian Malaveille, Nicholas E. Day, Bertil Forsberg, Gerard Hoek, Fabrizio Veglia, Carlos A. González, Vittorio Krogh, Herman Autrup, Paolo Vineis, Marco Peluso, Alison M. Dunning, Rosario Tumino, Vineis, P, Hoek, G, Krzyzanowski, M, VIGNA TAGLIANTI, F, Veglia, F, Airoldi, L, Autrup, H, Dunning, A, Garte, S, Hainaut, P, Malaveille, C, Matullo, G, Overvad, K, RAASCHOU NIELSEN, O, CLAVEL CHAPELON, F, Linseisen, J, Boeing, H, Trichopoulou, A, Palli, D, Peluso, M, Krogh, V, Tumino, R, Panico, Salvatore, BUENO DE MESQUITA, Hb, Peeters, Ph, Lund, Ee, Gonzalez, Ca, Martinez, C, Dorronsoro, M, Barricarte, A, Cirera, L, Quiros, Jr, Berglund, G, Forsberg, B, Day, Ne, Key, Tj, Saracci, R, Kaaks, R, and Riboli, E.
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,non-smokers ,Risk Assessment ,chemistry.chemical_compound ,Residence Characteristics ,Risk Factors ,Environmental health ,Air Pollution ,medicine ,Odds Ratio ,Humans ,ddc:610 ,Prospective Studies ,Risk factor ,Lung cancer ,Prospective cohort study ,Aged ,business.industry ,Incidence ,Case-control study ,Odds ratio ,Environmental exposure ,Environmental Exposure ,Middle Aged ,medicine.disease ,Confidence interval ,Surgery ,air pollution ,lung cancer ,prospective study ,Europe ,Logistic Models ,Oncology ,chemistry ,Case-Control Studies ,Female ,business ,Cotinine - 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 exsmokers (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 (NO2, PM10, SO2) 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 NO2 we found an odds ratio of 1.14 (95% CI, 0.78-1.67) for each increment of 10 μg/m3, and an odds ratio of 1.30 (1.02-1.66) for concentrations greater than 30 μg/m3. The association with NO2 did not change after adjustment by cotinine and additional potential confounders, including occupational exposures. No clear association was found with other pollutants. © 2006 Wiley-Liss, Inc.
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- 2006
16. DNA repair polymorphisms and cancer risk in non-smokers in a cohort study
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Elio Riboli, Ole Raaschou-Nielsen, Giuseppe Matullo, Marco Peluso, Alison M. Dunning, Aurelio Barricarte, H. B. Bueno-De-Mesquita, Gerard Hoek, Herman Autrup, J. R. Quirós, Salvatore Panico, Emmanuelle Gormally, Vittorio Krogh, Silvia Polidoro, R. Saracci, Paolo Vineis, Rudolph Kaaks, Domenico Palli, Carlos Martinez, J. Linseisen, Timothy J. Key, Luisa Airoldi, Christian Malaveille, Nicholas E. Day, P. H. M. Peeters, Fabrizio Veglia, R. Tumino, M. J. Tormo, Caroline Baynes, F. Clavel-Chapelon, Kim Overvad, Simonetta Guarrera, Eiliv Lund, Seymour Garte, H. Boeing, Miren Dorronsoro, Michal Krzyzanowski, Antonia Trichopoulou, Guillem Pera, Matullo, G, Dunning, Am, Guarrera, S, Baynes, C, Polidoro, S, Garte, S, Autrup, H, Malaveille, C, Peluso, M, Airoldi, L, Veglia, F, Gormally, E, Hoek, G, Krzyzanowski, M, Overvad, K, RAASCHOU NIELSEN, O, CLAVEL CHAPELON, F, Linseisen, J, Boeing, H, Trichopoulou, A, Palli, D, Krogh, V, Tumino, R, Panico, Salvatore, BUENO DE MESQUITA, Hb, Peeters, Ph, Lund, E, Pera, G, Martinez, C, Dorronsoro, M, Barricarte, A, Tormo, Mj, Quiros, Jr, Day, Ne, Key, Tj, Saracci, R, Kaaks, R, Riboli, E, and Vineis, P.
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Adult ,Male ,Risk ,Oncology ,Cancer Research ,Pathology ,medicine.medical_specialty ,DNA Repair ,DNA repair ,Biology ,non-smokers ,lung ,chronic obstructive pulmonary disease ,Cohort Studies ,Neoplasms ,Internal medicine ,Genotype ,Odds Ratio ,medicine ,Humans ,False Positive Reactions ,Prospective Studies ,ddc:610 ,oral-pharyngeal ,Lung cancer ,Prospective cohort study ,Aged ,Polymorphism, Genetic ,Bladder cancer ,Smoking ,Haplotype ,Case-control study ,Cancer ,General Medicine ,Middle Aged ,medicine.disease ,DNA repair polymorphisms ,laryngeal cancer ,leukaemia ,Case-Control Studies ,Multivariate Analysis ,Female - Abstract
Environmental carcinogens contained in air pollution, such as polycyclic aromatic hydrocarbons, aromatic amines or N-nitroso compounds, predominantly form DNA adducts but can also generate interstrand cross-links and reactive oxygen species. If unrepaired, such lesions increase the risk of somatic mutations and cancer. Our study investigated the relationships between 22 polymorphisms (and their haplotypes) in 16 DNA repair genes belonging to different repair pathways in 1094 controls and 567 cancer cases (bladder cancer, 131; lung cancer, 134; oral-pharyngeal cancer, 41; laryngeal cancer, 47; leukaemia, 179; death from emphysema and chronic obstructive pulmonary disease, 84). The design was a case-control study nested within a prospective investigation. Among the many comparisons, few polymorphisms were associated with the diseases at the univariate analysis: XRCC1-399 Gln/Gln variant homozygotes [odds ratios (OR) = 2.20, 95% confidence intervals (CI) = 1.16-4.17] and XRCC3-241 Met/Met homozygotes (OR = 0.51, 95% CI = 0.27-0.96) and leukaemia. The recessive model in the stepwise multivariate analysis revealed a possible protective effect of XRCC1-399Gln/Gln in lung cancer (OR = 0.22, 95% CI = 0.05-0.98), and confirmed an opposite effect (OR = 2.47, 95% CI = 1.02-6.02) in the leukaemia group. Our results also suggest that the XPD/ERCC1-GAT haplotype may modulate leukaemia (OR = 1.28, 95% CI = 1.02-1.61), bladder cancer (OR = 1.38, 95% CI = 1.06-1.79) and possibly other cancer risks. Further investigations of the combined effects of polymorphisms within these DNA repair genes, smoking and other risk factors may help to clarify the influence of genetic variation in the carcinogenic process. © 2006 Oxford University Press.
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- 2006
17. 4-Aminobiphenyl-hemoglobin adducts and risk of smoking-related disease in never smokers and former smokers in the European Prospective Investigation into Cancer and Nutrition prospective study
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Göran Hallmans, Michal Krzyzanowski, Luisa Airoldi, Antonia Trichopoulou, Aurelio Barricarte, Roberto Fanelli, Vittorio Krogh, Françoise Clavel-Chapelon, Christian Malaveille, Rodolfo Saracci, Nicholas E. Day, Herman Autrup, Carmen Martinez, Gerard Hoek, Pierre Hainaut, Carlo dell'Osta, Anne Tjønneland, Luca Manzi, Giuseppe Matullo, Bengt Järvholm, Hendrik B. Bueno-de-Mesquita, Domenico Palli, Fabrizio Veglia, Marco Peluso, Alison M. Dunning, Rosario Tumino, Jakob Linseisen, Kim Overvad, M. Dolores Chirlaque, Salvatore Panico, Elio Riboli, José Ramón Quirós, Miren Dorronsoro, Paolo Vineis, Antonio Agudo, Petra H.M. Peeters, Göran Berglund, Naomi E. Allen, Heiner Boeing, Seymour Garte, Luca Olgiati, Eiliv Lund, Alessandro Colombi, Rudolf Kaaks, Faculteit Diergeneeskunde, Airoldi, L, Vineis, P, Colombi, A, Olgiati, L, Dell'Osta, C, Fanelli, R, Manzi, L, Veglia, F, Autrup, H, Dunning, A, Garte, S, Hainaut, P, Hoek, G, Krzyzanowski, M, Malaveille, C, Matullo, G, Overvad, K, Tjonneland, A, CLAVEL CHAPELON, F, Linseisen, J, Boeing, H, Trichopoulou, A, Palli, D, Peluso, M, Krogh, V, Tumino, R, Panico, Salvatore, BUENO DE MESQUITA, Hb, Peeters, Ph, Lund, E, Agudo, A, Martinez, C, Dorronsoro, M, Barricarte, A, Chirlaque, Md, Quiros, Jr, Berglund, G, Jarvholm, B, Hallmans, G, Day, Ne, Allen, N, Saracci, R, Kaaks, R, and Riboli, E.
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Male ,Pathology ,medicine.medical_specialty ,Passive smoking ,Epidemiology ,former smokers ,4-Aminobiphenyl-hemoglobin adducts ,never smokers ,European Prospective Investigation into Cancer and Nutrition ,prospective study ,medicine.disease_cause ,Gastroenterology ,Tobacco smoke ,Hemoglobins ,Sex Factors ,Risk Factors ,Neoplasms ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Risk factor ,Prospective cohort study ,business.industry ,Smoking ,Case-control study ,Odds ratio ,Middle Aged ,Diergeneeskunde (DGNK) ,Oncology ,Case-Control Studies ,Population study ,Female ,Tobacco Smoke Pollution ,business ,Biomarkers - Abstract
The aim of this study was to evaluate whether biomarkers of environmental tobacco smoke exposure [i.e., 4-aminobiphenyl-hemoglobin (4-ABP-Hb) adducts] were predictive of the risk of tobacco-related cancers and diseases. We did a case-control 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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- 2005
18. Metabolic gene polymorphisms and lung cancer risk in non-smokers: An update of the GSEC study
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Sara, Raimondi, Paolo, Boffetta, Sisko, Anttila, Jürgen, Bröckmoller, Dorota, Butkiewicz, Ingolf, Cascorbi, Margie L, Clapper, Tommaso A, Dragani, Seymour, Garte, Andre, Gsur, Gerald, Haidinger, Ari, Hirvonen, Magnus, Ingelman-Sundberg, Ivan, Kalina, Qing, Lan, Vera Piera, Leoni, Loïc, Le Marchand, Stephanie J, London, Monica, Neri, Andrew C, Povey, Agneta, Rannug, Edyta, Reszka, David, Ryberg, Angela, Risch, Marjorie, Romkes, Alberto, Ruano-Ravina, Bernadette, Schoket, Monica, Spinola, Haruhiko, Sugimura, Xifeng, Wu, Emanuela, Taioli, Raimondi, S., Boffetta, P., Anttila, S., Bröckmoller, J., Butkiewicz, D., Cascorbi, I., Clapper, M.L., Dragani, T.A., Garte, S., Gsur, A., Haidinger, G., Hirvonen, A., Ingelman-Sundberg, M., Kalina, I., Lan, Q., Leoni, V.P., Marchand, L.L., London, S.J., Neri, M., Povey, A.C., Rannug, A., Reszka, E., Ryberg, D., Risch, A., Romkes, M., Ruano-Ravina, A., Schoket, B., Spinola, M., Sugimura, H., Wu, X., and Taioli, E.
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Lung Neoplasms ,Polymorphism, Genetic ,Racial Groups ,Environmental Exposure ,Adenocarcinoma ,United States ,respiratory tract diseases ,Amino Acid Substitution ,Carcinoma, Squamous Cell ,Cytochrome P-450 CYP1A1 ,Humans ,Genetic Predisposition to Disease ,Smoking Cessation ,Lung cancer ,Glutathione Transferase - Abstract
Background: Since genetic factors may play an important role in lung cancer development at low dose carcinogen exposure, non-smokers are a good model to study genetic susceptibility and its interaction with environmental factors. Materials and methods: We evaluated the role of the metabolic gene polymorphisms CYP1A1MspI, CYP1A1Ile462Val, GSTM1, and GSTT1 in non-smoker lung cancer patients from the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC). Non-smokers (defined as subjects who never smoked on a regular basis) were selected from the GSEC database. We pooled the raw data from 21 case-control studies for a total of 2764 Caucasians (555 cases and 2209 controls) and 383 Asians (113 cases and 270 controls). Tests of heterogeneity and of inclusion bias were performed. Results: A significant association between lung cancer and CYP1A1Ile462Val polymorphism was observed in Caucasians (adjusted OR = 2.04, 95% CI 1.17-3.54). GSTT1 deletion seems to be a risk factor for lung cancer in Caucasian non smokers only when the analysis was restricted to studies including healthy controls (adjusted OR = 1.66, 95% CI 1.12-2.46). A protective effect on lung cancer was observed with the combination of CYP1A1 wild type, GSTM1 null, and GSTT1 non-null genotypes. None of the analysed polymorphisms were associated with lung cancer in Asian non-smokers. Discussion: Our analysis confirms previous findings that CYP1A1Ile462Val polymorphism may play a role in lung carcinogenesis in Caucasian non-smokers. © 2005 Elsevier B.V. All rights reserved.
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- 2005
19. Environmental tobacco smoke and risk of respiratory cancer andchronic obstructive pulmonary disease in former smokers and never smokers in the EPIC prospective study
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Emmanuelle Gormally, R. Saracci, F. Clavel-Chapelon, Roberta Pastorelli, Herman Autrup, L Olgiati, Krogh, Pierre Hainaut, Anne Tjønneland, Fabrizio Veglia, B. Bueno-de-Mesquita, Göran Hallmans, Luisa Airoldi, Göran Berglund, R. Tumino, Seymour Garte, Christian Malaveille, P. H. M. Peeters, D. Palli, H. Boeing, Marco Peluso, Alison M. Dunning, Kim Overvad, Elio Riboli, Paolo Vineis, Giuseppe Matullo, Salvatore Panico, Vineis, P, Airoldi, L, Veglia, P, Olgiati, L, Pastorelli, R, Autrup, H, Dunning, A, Garte, S, Gormally, E, Hainaut, P, Malaveille, C, Matullo, G, Peluso, M, Overvad, K, Tjonneland, A, CLAVEL CHAPELON, F, Boeing, H, Krogh, V, Palli, D, Panico, Salvatore, Tumino, R, BUENO DE MESQUITA, B, Peeters, P, Berglund, G, Hallmans, G, Saracci, R, and Riboli, E.
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medicine.medical_specialty ,plasma cotinine ,pharynx ,Passive smoking ,environmental tobacco smoke ,medicine.disease_cause ,Tobacco smoke ,lung ,chemistry.chemical_compound ,Internal medicine ,death ,medicine ,Intensive care medicine ,Lung cancer ,Prospective cohort study ,General Environmental Science ,business.industry ,larynx cancer ,Respiratory disease ,General Engineering ,Cancer ,General Medicine ,medicine.disease ,European Prospective Investigation into Cancer and Nutrition ,chemistry ,Papers ,General Earth and Planetary Sciences ,Cotinine ,business - Abstract
Objectives To investigate the association between environmental tobacco smoke, plasma cotinine concentration, and respiratory cancer or death. Design Nested case-control study within the European prospective investigation into cancer and nutrition (EPIC). Participants 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. Main outcome measures Newly diagnosed cancer of lung, pharynx, and larynx; deaths from chronic obstructive pulmonary disease or emphysema. Plasma cotinine concentration was measured in 1574 people. Results 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). Conclusions 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.
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- 2005
20. Amount of DNA in plasma and cancer risk: A prospective study
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Göran Hallmans, Kim Overvad, H. Bas Bueno-de-Mesquita, Carmen Martinez, Teresa Norat, Eiliv Lund, Paolo Boffetta, Emmanuelle Gormally, Paolo Vineis, Miren Dorronsoro, Salvatore Panico, Françoise Clavel-Chapelon, Rudolf Kaaks, Antonia Trichopoulou, Domenico Palli, M. José Tormo, Christian Malaveille, Nicholas E. Day, Marco Peluso, Alison M. Dunning, Rosario Tumino, Elio Riboli, Pierre Hainaut, J. Ramón Quirós, Giuseppe Matullo, Heiner Boeing, Anne Tjønneland, Seymour Garte, Elodie Caboux, Rodolfo Saracci, Vittorio Krogh, Herman Autrup, Petra H.M. Peeters, Timothy J. Key, Luisa Airoldi, Aurelio Barricarte, Carlos A. González, Göran Berglund, Fabrizio Veglia, Gormally, E, Hainaut, P, Caboux, E, Airoldi, L, Autrup, H, Malaveille, C, Dunning, A, Garte, S, Matullo, G, Overvad, K, Tjonneland, A, CLAVEL CHAPELON, F, Boffetta, P, Boeing, H, Trichopoulou, A, Palli, D, Krogh, V, Tumino, R, Panico, Salvatore, BUENO DE MESQUITA, Hb, Peeters, Ph, Lund, E, Gonzalez, Ca, Martinez, C, Dorronsoro, M, Barricarte, A, Tormo, Mj, Quiros, Jr, Berglund, G, Hallmans, G, Day, Ne, Key, Tj, Veglia, F, Peluso, M, Norat, T, Saracci, R, Kaaks, R, Riboli, E, Vineis, P., Gormally, E., Hainaut, P., Caboux, E., Airoldi, L., Autrup, H., Malaveille, C., Dunning, A., Garte, S., Matullo, G., Overvad, K., Tjonneland, A., Clavel-Chapelon, F., Boffetta, P., Boeing, H., Trichopoulou, A., Palli, D., Krogh, V., Tumino, R., Panico, S., Bueno-De-Mesquita, H.B., Peeters, P.H., Lund, E., Gonzalez, C.A., Martinez, C., Dorronsoro, M., Barricarte, A., Tormo, M.J., Quiros, J.R., Berglund, G., Hallmans, G., Day, N.E., Key, T.J., Veglia, F., Peluso, M., Norat, T., Saracci, R., Kaaks, R., and Riboli, E.
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Population ,Gastroenterology ,Pulmonary Disease, Chronic Obstructive ,Risk Factors ,Neoplasms ,Internal medicine ,Odds Ratio ,medicine ,Humans ,cancer ,plasmatic DNA ,prospective studies ,molecular repidemiology ,Risk factor ,Prospective cohort study ,education ,Aged ,COPD ,education.field_of_study ,Leukemia ,business.industry ,Cancer ,DNA ,Odds ratio ,Middle Aged ,Prognosis ,medicine.disease ,European Prospective Investigation into Cancer and Nutrition ,Oncology ,Case-Control Studies ,Amount of DNA in plasma and cancer risk ,Immunology ,Female ,business ,Blood drawing - Abstract
Levels of plasma DNA concentrations in cancer patients have been shown to be higher than the plasma DNA concentrations found in healthy subjects. The value of plasma DNA levels for development of neoplastic or pulmonary disease was evaluated in a large prospective study. Plasma samples (n = I,184) were analyzed from 776 controls, 359 cases of cancer (lung, bladder, oral cavity, pharynx, larynx, leukemia) and 49 deaths from chronic obstructive pulmonary disease (COPD), including never smokers and ex-smokers, from 9 countries across Europe. The amount of plasma DNA was variable across the European Prospective Investigation into Cancer and Nutrition (EPIC) centers. High DNA concentrations in some centers might be due to the type of population recruited and/or the treatment of the samples. An elevated and statistically significant odds ratio (OR) was found for COPD deaths (OR = 2.53; 95% CI = 1.06-6.02), while nonsignificant increased ORs were present for oral cancers, cancers of the pharynx and larynx and leukemia. When the analyses were stratified by time since recruitment (below or above 36 months), the increased ORs were limited to the more recent period of recruitment, i.e., a time elapsed between blood drawing and disease onset lower than 36 months. This was particularly true for COPD deaths (OR = 12.7; 95% CI = 1.57-103) and leukemia (OR = 2.37; 95% CI = 1.20-4.67). © 2004 Wiley-Liss, Inc.
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- 2004
21. Comparison of DNA adduct levels in nasal mucosa, lymphocytes and bronchial mucosa of cigarette smokers and interaction with metabolic gene polymorphisms
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Emanuela Taioli, Roberto Quaglia, Giovanni Margarino, Marco Peluso, Riccardo Puntoni, Raffaella Felletti, Seymour Garte, Marina Buratti, Francesca Stea, Marcello Ceppi, Armelle Munnia, Monica Neri, Stefano Bonassi, and Carlo Mereu
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Male ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Genotype ,Biopsy ,Population ,Bronchi ,Mucous membrane of nose ,Biology ,medicine.disease_cause ,Gastroenterology ,DNA Adducts ,Gene interaction ,Internal medicine ,DNA adduct ,Cytochrome P-450 CYP1A1 ,medicine ,Humans ,Bronchial Biopsy ,Drug Interactions ,Genetic Predisposition to Disease ,Lymphocytes ,Lung cancer ,education ,Nose ,Aged ,Glutathione Transferase ,education.field_of_study ,Polymorphism, Genetic ,Smoking ,General Medicine ,Middle Aged ,respiratory system ,medicine.disease ,Nasal Mucosa ,medicine.anatomical_structure ,Immunology ,Female ,Carcinogenesis - Abstract
The recent introduction of biomarkers in population studies of lung cancer has improved the traditional epidemiological approach, especially in the detection of high risk groups. Many inhalable carcinogens form DNA adducts, an initial event in lung carcinogenesis, and therefore the identification of easily accessible sources of DNA for population studies is considered a leading priority in the field. In this study we compared the frequency of DNA adducts in samples from nasal brushing, bronchial biopsy and peripheral blood lymphocytes (PBL) in a group of 55 subjects, both smokers and non-smokers, undergoing bronchoscopy for diagnostic purposes. Polymorphisms in the CYP1A1, GSTM1 and GSTT1 genes were also evaluated. The level of DNA adducts measured by (32)P-labelling assay in nasal mucosa (10(8) relative adduct level, mean +/- SD 1.10 +/- 0.66) was higher than in bronchial mucosa (0.82 +/- 0.36) and in PBL (0.54 +/- 0.39, P < 0.01). DNA adducts measured in nasal mucosa and in PBL were correlated with those in bronchial mucosa (P < 0.01 and P < 0.05, respectively). DNA adducts in smokers were significantly increased in both nasal mucosa and PBL, with a significant dose-response linear trend (P < 0.05). No significant effect on DNA adduction of the genetic polymorphisms investigated was found. Nasal mucosa brushing proved to be a suitable procedure for the (32)P-labelling assay and its use in population studies should be further explored.
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- 2004
22. Association of metabolic gene polymorphisms with tobacco consumption in healthy controls
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Luis Felipe Ribeiro Pinto, Ari Hirvonen, Richard C. Strange, Paolo Vineis, Lisa Bathum, Wei Zheng, Haruhiko Sugimura, Jordi To-Figueras, Bernadette Schoket, Masahiro Kihara, Herman Autrup, Seymour Garte, Salagovic J, Dorota Butkiewicz, Maria Celeste Lechner, C. Bouchardy, Emanuela Taioli, Janeric Seidegård, Margie L. Clapper, Minii C. Yu, Helena Baranova, Isabelle Stücker, Matty P. Weijenberg, Johannes J. Manni, Fritz F. Parl, Ann K. Daly, Gareth J. Morgan, Tatyana G. Duzhak, Klaus Golka, Shunji Morita, Allan Hildesheim, Timothy R. Rebbeck, Yoshio Oda, Daniel Sinnett, Vessela N. Kristensen, Christine B. Ambrosone, Heon Kim, Aage Haugen, Takahiko Katoh, Giacomo Muzi, Ingolf Cascorbi, Magnus Ingelman-Sundberg, Yannis Alamanos, Ling L. Hsieh, Daehee Kang, Christine Maugard, Agneta Rannug, Marjorie Romkes, Simone Benhamou, Masako Ono-Kihara, Paola Pedotti, Wilbert H.M. Peters, Valle Nazar-Stewart, Vita Dolzan, Peter G. Shields, Philip Lazarus, Kim M. Smits, Farker K, Judith L. Autrup, Paolo Boffetta, Edith Sim, David W. Hein, Stephanie J. London, Ivan Kalina, Jürgen Brockmöller, Loic Le Marchand, Angela Risch, Pierre Kremers, Christiane Coutelle, Chikako Kiyohara, RS: NUTRIM School of Nutrition and Translational Research in Metabolism, RS: CAPHRI School for Public Health and Primary Care, RS: GROW - School for Oncology and Reproduction, Epidemiologie, Keel-, Neus- en Oorheelkunde, Smits, K.M., Benhamou, S., Garte, S., Weijenberg, M.P., Alamanos, Y., Ambrosone, C., Autrup, H., Autrup, J.L., Baranova, H., Bathum, L., Boffetta, P., Bouchardy, C., Brockmoller, J., Butkiewicz, D., Cascorbi, I., Clapper, M.L., Coutelle, C., Daly, A.K., Muzi, G., Dolzan, V., Duzhak, T.G., Farker, K., Golka, K., Haugen, A., Hein, D.W., Hildesheim, A., Hirvonen, A., Hsieh, L.L., Ingelman-Sundberg, M., Kalina, I., Kang, D., Katoh, T., Kihara, M., Ono-Kihara, M., Kim, H., Kiyohara, C., Kremers, P., Lazarus, P., Le Marchand, L., Lechner, M.C., London, S., Manni, J.J., Maugard, C.M., Morgan, G.J., Morita, S., Nazar-Stewart, V., Kristensen, V.N., Oda, Y., Parl, F.F., Peters, W.H.M., Rannug, A., Rebbeck, T., Pinto, L.F.R., Risch, A., Romkes, M., Šalagovic, J., Schoket, B., Seidegard, J., Shields, P.G., Sim, E., Sinnett, D., Strange, R.C., Stucker, I., Sugimura, H., To-Figueras, J., Vineis, P., Yu, M.C., Zheng, W., Pedotti, P., and Taioli, E.
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Cancer Research ,Arylamine N-Acetyltransferase ,Association of metabolic gene polymorphisms with tobacco ,Biology ,Isozyme ,Tobacco smoke ,03 medical and health sciences ,0302 clinical medicine ,Polymorphism (computer science) ,Genotype ,Genetic predisposition ,Humans ,Genetic Predisposition to Disease ,Genetic variability ,Gene ,Carcinogen ,Molecular diagnosis, prognosis and monitoring [UMCN 1.2] ,030304 developmental biology ,Glutathione Transferase ,Genetics ,0303 health sciences ,Polymorphism, Genetic ,Smoking ,3. Good health ,Isoenzymes ,Oncology ,Glutathione S-Transferase pi ,030220 oncology & carcinogenesis - Abstract
Contains fulltext : 58545.pdf (Publisher’s version ) (Closed access) Polymorphisms in genes that encode for metabolic enzymes have been associated with variations in enzyme activity between individuals. Such variations could be associated with differences in individual exposure to carcinogens that are metabolized by these genes. In this study, we examine the association between polymorphisms in several metabolic genes and the consumption of tobacco in a large sample of healthy individuals. The database of the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens was used. All the individuals who were controls from the case-control studies included in the data set with information on smoking habits and on genetic polymorphisms were selected (n = 20938). Sufficient information was available on the following genes that are involved in the metabolism of tobacco smoke constituents: CYP1A1, GSTM1, GSTT1, NAT2 and GSTP1. None of the tested genes was clearly associated with smoking behavior. Information on smoking dose, available for a subset of subjects, showed no effect of metabolic gene polymorphisms on the amount of smoking. No association between polymorphisms in the genes studied and tobacco consumption was observed; therefore, no effect of these genes on smoking behavior should be expected.
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- 2004
23. Polymorphisms in CYP1A1, GSTM1, GSTT1 and lung cancer below the age of 45 years
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Dorota Butkiewicz, Ari Hirvonen, Emanuelle Taioli, Marjorie Romkes, Laura Gaspari, Ivan Kalina, Seymour Garte, Stephanie J. London, Pierre Kremers, Aage Haugen, Agneta Rannug, Paolo Boffetta, Simone Benhamou, Janeric Seidegård, Ingolf Cascorbi, Richard C. Strange, Jürgen Brockmöller, Loic Le Marchand, Vita Dolzan, Jordi To-Figueras, Isabelle Stücker, Bernadette Schoket, Margie L. Clapper, Kirsti Husgafvel-Pursiainen, Molecular and Genetic Epidemiology Unit (IRCCS), IRCCS, Unité de Recherches en Epidémiologie des Cancers, Institut National de la Santé et de la Recherche Médicale (INSERM), Unit of Environment Cancer Epidemiology, IARC, Institute of Clinical Pharmacology, Georg-August-University [Göttingen], Institute of Clinical Pharmacology of Gliwice, Ernst Moritz Arndt University, Fox Chase Cancer Centre, University of Ljubljana, National Institue of Occupational Health, National Institue of Occupational Health of Norway, Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Unit of Excellence for Psychosocial Factors, P.J. Safarik University, Institut de Pathologie, CHU Liège, University of Hawai‘i [Mānoa] (UHM), National Institute for Environmental Health Sciences Research Triangle Park, Karolinska Institutet [Stockholm], Department of Computer Science - University of Pittsburgh, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), National Institute of Environmental Health, Lund University [Lund], Keele University [Keele], Recherches épidémiologiques et statistiques sur l'environnement et la santé., Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospital Clinic Provincial, Environmental and Occupational Health Sciences Institute (EOHSI), EOHSI, Georg-August-University = Georg-August-Universität Göttingen, and Secretariat, U754
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Oncology ,Male ,Lung Neoplasms ,MESH: Chi-Square Distribution ,Databases, Factual ,Epidemiology ,0302 clinical medicine ,Risk Factors ,MESH: Risk Factors ,Genotype ,Medicine ,Young adult ,Age of Onset ,Glutathione Transferase ,0303 health sciences ,Respiratory disease ,Smoking ,MESH: Genetic Predisposition to Disease ,General Medicine ,respiratory system ,MESH: Case-Control Studies ,3. Good health ,MESH: Cytochrome P-450 CYP1A1 ,030220 oncology & carcinogenesis ,Female ,Adult ,medicine.medical_specialty ,MESH: Smoking ,MESH: Age of Onset ,MESH: Factor Analysis, Statistical ,Genetic determinism ,03 medical and health sciences ,Internal medicine ,MESH: Polymorphism, Genetic ,Genetic predisposition ,Cytochrome P-450 CYP1A1 ,Humans ,Genetic Predisposition to Disease ,Lung cancer ,Carcinogen ,030304 developmental biology ,MESH: Glutathione Transferase ,Chi-Square Distribution ,Polymorphism, Genetic ,MESH: Humans ,business.industry ,MESH: Adult ,medicine.disease ,MESH: Databases, Factual ,MESH: Male ,respiratory tract diseases ,MESH: Lung Neoplasms ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,Case-Control Studies ,Immunology ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,business ,Factor Analysis, Statistical ,MESH: Female - Abstract
Background A genetic component of early-onset lung cancer has been suggested. The role of metabolic gene polymorphisms has never been studied in young lung cancer cases. Phase 1 and Phase 2 gene polymorphisms are involved in tobacco carcinogens' metabolism and therefore in lung cancer risk. Methods The effect of metabolic gene polymorphisms on lung cancer at young ages was studied by pooling data from the Genetic Susceptibility to Environmental Carcinogens (GSEC) database. All primary lung cancer cases of both sexes who were Caucasian and less than or equal to45 years of age at diagnosis, and the corresponding controls were selected. We obtained 261 cases and 1452 controls. Results There was a marginally significant association between lung cancer and GST1 null genotype (OR = 1.2; 95% Cl: 1.0-1.6), and a significant association between lung cancer and the homozygous CYP1A1 Msp1 variant allele (CYP1A1*2A and *2B) genotype (OR = 4.7 95% Cl: 1.2-19.0). When data were stratified by smoking status, the association between CYP1A1 genotype and lung cancer was confined to never smokers. Conclusions These results suggest that metabolic genetic factors play a role in lung cancer developing at young ages. (Less)
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- 2003
24. Polymorphisms of Drug-Metabolizing Enzymes in healthy Nonagenarians and Centenarians: difference at GSTT1 locus
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Emanuela Taioli, Stefano Bertolini, Daniela Monti, Seymour Garte, Daniela Mari, Massimiliano Bonafè, Claudio Franceschi, and Daniela Marinelli
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Adult ,Male ,Aging ,Heterozygote ,Adolescent ,Genotype ,media_common.quotation_subject ,Biophysics ,Locus (genetics) ,Biology ,Biochemistry ,chemistry.chemical_compound ,Gene Frequency ,Cytochrome P-450 CYP1A1 ,Humans ,Child ,Molecular Biology ,Gene ,Carcinogen ,media_common ,Aged ,Glutathione Transferase ,Genetics ,chemistry.chemical_classification ,Aged, 80 and over ,Polymorphism, Genetic ,Successful aging ,Homozygote ,Longevity ,Cell Biology ,Glutathione ,Middle Aged ,Enzyme ,chemistry ,Ageing ,Child, Preschool ,Female - Abstract
Drug metabolizing enzymes are involved in the detox- ification of several drugs, environmental substances, and carcinogenic compounds, and their polymorphisms have been associated with risk for a variety of cancer. In this paper, we compared the frequency of polymor- phisms in cytochrome P450-1A1 gene (CYP1A1), a phase 1 gene (oxidation, activation), and of two polymorphisms of glutathione S-transferase enzymes (GSTM1, GSTT1), two phase 2 genes (conjugation, detoxification). Two groups were studied and compared, i.e., 94 nonagenari- ans and centenarians and 418 control subjects of younger age. A significant difference in the proportion of nonagenarians and centenarians homozygotes for a GSTT1 deletion (28%) was observed in comparison to control subjects (19%, P 5 0.03). The distribution of the other gene polymorphisms did not differ in the two groups. These findings on phase 2 drug-metabolizing en- zyme gene polymorphisms may help in disentangling gene-environmental interactions which can have a role in successful aging and longevity, as well as in cancer incidence in the oldest old. © 2001 Academic Press
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- 2001
25. Molecular Epidemiology of Chronic Diseases
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Chris Wild, Paolo Vineis, Seymour Garte, Chris Wild, Paolo Vineis, and Seymour Garte
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- Molecular epidemiology, Chronic diseases--Epidemiology, Biochemical markers
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'I think this is an excellent book–I recommend it to anyone involved in molecular epidemiology... The 26 chapters are written by topic specialists, in an explanatory, east to read style.'–BTS Newsletter, Summer 2009'This text provides an accessible and useful handbook for the epidemiologist who wants to survey the field, to become better informed, to look at recent developments and get some background on these or simply to appreciate further the relatively rapid changes in informatic and analytical technologies which increasingly will serve and underpin future epidemiological studies. One of the strengths in this book is the extensive array of practical illustrative examples, and it would also in my opinion have useful potential as a teaching text.'–American Journal of Human Biology, March 2009 With the sequencing of the human genome and the mapping of millions of single nucleotide polymorphisms, epidemiology has moved into the molecular domain. Scientists can now use molecular markers to track disease-associated genes in populations, enabling them to study complex chronic diseases that might result from the weak interactions of many genes with the environment. Use of these laboratory generated biomarker data and an understanding of disease mechanisms are increasingly important in elucidating disease aetiology. Molecular Epidemiology of Disease crosses the disciplinary boundaries between laboratory scientists, epidemiologists, clinical researchers and biostatisticians and is accessible to all these relevant research communities in focusing on practical issues of application, rather than reviews of current areas of research. Covers categories of biomarkers of exposure, susceptibility and disease Includes chapters on novel technologies: genomics, transcriptomics, proteomics and metabonomics, which are increasingly finding application in population studies Emphasizes new statistical and bioinformatics approaches necessitated by the large data sets generated using these new methodologies Demonstrates the potential applications of laboratory techniques in tackling epidemiological problems while considering their limitations, including the sources of uncertainty and inaccuracy Discusses issues such as reliability (compared to traditional epidemiological methods) and the timing of exposure Explores practical elements of conducting population studies, including biological repositories and ethics Molecular Epidemiology of Disease provides an easy-to-use, clearly presented handbook that allows epidemiologists to understand the specifics of research involving biomarkers, and laboratory scientists to understand the main issues of epidemiological study design and analysis. It also provides a useful tool for courses on molecular epidemiology, using many examples from population studies to illustrate key concepts and principles.
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- 2008
26. Alcohol Dehydrogenase 3, Glutathione S-transferase M1 and T1 Polymorphisms, Alcohol Consumption and Hepatocellular Carcinoma (Italy).
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Loredana Covolo, Umberto Gelatti, Renato Talamini, Seymour Garte, Paola Trevisi, Silvia Franceschi, Michela Franceschini, Fabio Barbone, Alessandro Tagger, Maria Lisa Ribero, Giovanni Parrinello, Valter Donadon, Giuseppe Nardi, and Francesco Donato
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- 2005
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27. Comparison of DNA adduct levels in nasal mucosa, lymphocytes and bronchial mucosa of cigarette smokers and interaction with metabolic gene polymorphisms.
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Marco Peluso, Monica Neri, Giovanni Margarino, Carlo Mereu, Armelle Munnia, Marcello Ceppi, Marina Buratti, Raffaella Felletti, Francesca Stea, Roberto Quaglia, Riccardo Puntoni, Emanuela Taioli, Seymour Garte, and Stefano Bonassi
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GENES ,DNA ,CIGARETTE smokers ,GENETIC toxicology - Abstract
The recent introduction of biomarkers in population studies of lung cancer has improved the traditional epidemiological approach, especially in the detection of high risk groups. Many inhalable carcinogens form DNA adducts, an initial event in lung carcinogenesis, and therefore the identification of easily accessible sources of DNA for population studies is considered a leading priority in the field. In this study we compared the frequency of DNA adducts in samples from nasal brushing, bronchial biopsy and peripheral blood lymphocytes (PBL) in a group of 55 subjects, both smokers and non-smokers, undergoing bronchoscopy for diagnostic purposes. Polymorphisms in the CYP1A1, GSTM1 and GSTT1 genes were also evaluated. The level of DNA adducts measured by 32P-labelling assay in nasal mucosa (108 relative adduct level, mean SD 1.10 0.66) was higher than in bronchial mucosa (0.82 0.36) and in PBL (0.54 0.39, P < 0.01). DNA adducts measured in nasal mucosa and in PBL were correlated with those in bronchial mucosa (P < 0.01 and P < 0.05, respectively). DNA adducts in smokers were significantly increased in both nasal mucosa and PBL, with a significant doseresponse linear trend (P < 0.05). No significant effect on DNA adduction of the genetic polymorphisms investigated was found. Nasal mucosa brushing proved to be a suitable procedure for the 32P-labelling assay and its use in population studies should be further explored. [ABSTRACT FROM AUTHOR]
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- 2004
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28. The effects of diet on DNA bulky adduct levels are strongly modified by GSTM1 genotype: a study on 634 subjects.
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Domenico Palli, Giovanna Masala, Marco Peluso, Laura Gaspari, Vittorio Krogh, Armelle Munnia, Salvatore Panico, Calogero Saieva, Rosario Tumino, Paolo Vineis, and Seymour Garte
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GENES ,DEOXYRIBOSE ,GENETIC research ,VITAMIN E - Abstract
Frequent consumption of fresh fruit and vegetables, and polymorphisms in the detoxifying enzyme glutathione S-transferase M1 (GSTM1) and other metabolic genes have been shown to modulate cancer risk at some sites. We have shown recently that DNA adducts, a reliable indicator of genotoxic damage and, possibly, of cancer risk, are modulated by plasma levels of selected micronutrients. Here we further investigate the association between DNA adduct levels and consumption of major food groups and foods, and the estimated dietary intake of nutrients, taking into account the possible modifying effect of metabolic polymorphisms, in a larger sample of 634 healthy adults enrolled in a prospective study in Italy. DNA adducts and five polymorphic metabolic genotypes (GSTM1, GSTT1, NAT2, CYP1A1 and MTHFR) were determined in peripheral leukocytes by using 32P-postlabeling technique and PCR methods. DNA bulky adducts (mean: 7.82 0.40/109 nt) were detected in 482/634 samples (76.0%). Overall, DNA adduct levels were significantly and inversely associated with the intake of raw leafy vegetables (P = 0.02), non-citrus fruits (P = 0.04), potassium (P = 0.01) and -carotene (P = 0.05). No association was evident with the five genotypes. Stratification by GSTM1 genotype showed strong inverse associations of DNA adduct levels with increasing consumption of all vegetables combined (P = 0.04), leafy vegetables (P = 0.004), raw leafy vegetables (P = 0.002) and fish (P = 0.03) among 307 GSTM1-null subjects; strong inverse associations also emerged with estimated dietary intakes of -carotene (P = 0.004), vitamin E (P = 0.004), niacin (P = 0.02) and potassium (P = 0.01). In contrast, no association emerged among 295 subjects with a GSTM1-wild genotype. Overall, statistically significant interactions in predicting DNA adduct levels were observed between the GSTM1-null genotype and consumption of leafy vegetables (P = 0.01), white meat (P = 0.04), and intake of vitamin C (P = 0.04), vitamin E (P = 0.05) and -carotene (P = 0.02). Our results suggest that the role of a diet rich in antioxidants in preventing or reducing DNA adduct formation is restricted to subjects lacking the detoxifying activity of GSTM1 isoenzyme (~50% of the general population). [ABSTRACT FROM AUTHOR]
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- 2004
29. Locus-specific genetic diversity between human populations: An analysis of the literature.
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Seymour Garte
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- 2003
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30. Leptin receptor Gln223Arg polymorphism and breast cancer risk in Nigerian women: A case control study
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Robert E. Ferrell, Joseph M. Zmuda, Emmanuel E. O. Uche, Lewis H. Kuller, Seymour Garte, Michael N. Okobia, Emanuela Taioli, Clareann H. Bunker, Stanley N.C. Anyanwu, and Emmanuel Ezeome
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medicine.medical_specialty ,Cancer Research ,Glutamine ,Nigeria ,Breast Neoplasms ,Arginine ,lcsh:RC254-282 ,Polymorphism, Single Nucleotide ,Breast cancer ,Gene Frequency ,Risk Factors ,Internal medicine ,Genetics ,Humans ,Medicine ,Outpatient clinic ,Genetic Predisposition to Disease ,Allele frequency ,Glucagon-like peptide 1 receptor ,Leptin receptor ,business.industry ,Leptin ,Carcinoma, Ductal, Breast ,Case-control study ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Postmenopause ,Endocrinology ,Premenopause ,Oncology ,Case-Control Studies ,Interleukin-21 receptor ,Receptors, Leptin ,Female ,business ,Polymorphism, Restriction Fragment Length ,Signal Transduction ,Research Article - Abstract
Background Leptin, a 16 kDa polypeptide hormone, implicated in various physiological processes, exerts its action through the leptin receptor, a member of the class I cytokine receptor family. Both leptin and leptin receptor have recently been implicated in processes leading to breast cancer initiation and progression in animal models and humans. An A to G transition mutation in codon 223 in exon 6 of the leptin receptor gene, resulting in glutamine to arginine substitution (Gln223Arg), lies within the first of two putative leptin-binding regions and may be associated with impaired signaling capacity of the leptin receptor. This study was designed to assess the role of this polymorphism in breast cancer susceptibility in Nigerian women. Methods We utilized a polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) assay to evaluate the association between the Gln223Arg polymorphism of the leptin receptor gene and breast risk in Nigeria in a case control study involving 209 women with breast cancer and 209 controls without the disease. Study participants were recruited from surgical outpatient clinics and surgical wards of four University Teaching Hospitals located in Midwestern and southeastern Nigeria between September 2002 and April 2004. Results Premenopausal women carrying at least one LEPR 223Arg allele were at a modestly increased risk of breast cancer after adjusting for confounders (OR = 1.8, 95% confidence interval [CI] 1.0–3.2, p = 0.07). There was no association with postmenopausal breast cancer risk (OR = 0.9, 95% CI 0.4–1.8, p = 0.68). Conclusion Our results suggest that the LEPR Gln223Arg polymorphism in the extracellular domain of the LEPR receptor gene is associated with a modestly increased risk of premenopausal breast cancer in Nigerian women.
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31. Prostaglandins Fail to Elevate Cyclic AMP Levels in Mouse Epidermis In Vivo and In Vitro
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Seymour Garte and Sidney Belman
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Mice, Inbred ICR ,medicine.medical_specialty ,integumentary system ,medicine.medical_treatment ,Cell Biology ,Dermatology ,Biology ,Biochemistry ,In vitro ,Cell Line ,Cell biology ,Mice ,Endocrinology ,Mouse Epidermis ,In vivo ,Internal medicine ,Cyclic AMP ,Prostaglandins ,medicine ,Animals ,Female ,Molecular Biology ,Skin ,Prostaglandin E - Abstract
Prostaglandin E 1 had no effect on mouse epidermal cyclic AMP levels either when applied percutaneously to shaven skin or when incubated in vitro with epidermal homogenates. Neither prostaglandin E 1 nor E 2 had any effect on cyclic AMP levels in a line of cultured mouse epidermal cells at doses from 0.1–10 μM.
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32. Leptin levels and leptin receptor polymorphism frequency in healthy populations
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Jiangying Chen, Camille Ragin, Emanuela Taioli, Michael N. Okobia, Francesmary Modugno, Cher M. Dallal, and Seymour Garte
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Cancer Research ,medicine.medical_specialty ,Epidemiology ,Population ,Adipose tissue ,03 medical and health sciences ,0302 clinical medicine ,Polymorphism (computer science) ,Internal medicine ,Genotype ,medicine ,10. No inequality ,education ,030304 developmental biology ,0303 health sciences ,education.field_of_study ,Leptin receptor ,business.industry ,Leptin ,medicine.disease ,Obesity ,Proceedings ,Endocrinology ,Infectious Diseases ,Oncology ,030220 oncology & carcinogenesis ,Population study ,business - Abstract
Background The leptin receptor gene (LEPR) polymorphism Q223R is one of the most common in the general population, and is thought to be associated with an impaired signaling capacity of the leptin receptor and with higher mean circulating levels of leptin. Leptin is a hormone primarily produced in adipose tissue. Increased levels of leptin have been positively correlated with obesity. We have determined the frequency of the leptin receptor polymorphism (LEPR Q223R) in healthy populations from various ethnic groups, and compared plasma leptin levels across the LEPR Q223R polymorphism in healthy African-Caribbean and Caucasian women. Results The study population consists of 1,418 healthy subjects from various ethnic groups. The LEPR Q223R homozygous variant was observed overall in 19% of subjects (n = 1,418), with significant differences based on self reported ethnicity: the proportion of subjects with the homozygous variant was lower in Caucasians (14%, n = 883) than in African-Caribbean (n = 194), African-American (n = 36) and Asian/other ethnic groups (n = 26), (35%, 33% and 34.6% respectively); the frequency in Africans (20%), was similar to the overall study population. The mean ± standard deviation (SD), circulating leptin levels for African-Caribbean women was 44.7 ± 31.4 ng/ml, while for Caucasian women the mean was 42.4 ± 34.8 ng/ml. Adjusted circulating leptin levels in post-menopausal Caucasian women who were LEPR Q223R homozygous variant were marginally statistically significantly higher than in women with the wild-type genotype (p = 0.098). No significant differences in leptin levels by genotype were observed for African-Caribbean women, (heterozygous: p = 0.765, homozygous variant: p = 0.485). Conclusion These findings suggest an association between mean circulating leptin levels and the LEPR Q223R genotype among post-menopausal Caucasian women.
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33. Comparison of estrogens and estrogen metabolites in human breast tissue and urine
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Annie Im, Emanuela Taioli, Gretchen M. Ahrendt, Seymour Garte, Timothy D. Veenstra, and Xia Xu
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Adult ,medicine.medical_specialty ,lcsh:QH471-489 ,medicine.drug_class ,Metabolite ,Urinary system ,CYP1B1 ,Estrone ,Breast Neoplasms ,Urine ,Biology ,Polymorphism, Single Nucleotide ,lcsh:Gynecology and obstetrics ,chemistry.chemical_compound ,Breast cancer ,Endocrinology ,Cytochrome P-450 Enzyme System ,Gene Frequency ,Leucine ,Internal medicine ,medicine ,Metabolome ,Humans ,lcsh:Reproduction ,Breast ,skin and connective tissue diseases ,lcsh:RG1-991 ,Aged ,Estradiol ,Research ,Carcinoma, Ductal, Breast ,Obstetrics and Gynecology ,Estrogens ,Valine ,Middle Aged ,medicine.disease ,chemistry ,Reproductive Medicine ,Estrogen ,Case-Control Studies ,Cytochrome P-450 CYP1B1 ,Female ,Aryl Hydrocarbon Hydroxylases ,Metabolic Networks and Pathways ,Developmental Biology - Abstract
Background An important aspect of the link between estrogen and breast cancer is whether urinary estrogen levels are representative of the intra-tissue levels of bioavailable estrogens. Methods This study compares 15 estrogen and estrogen metabolite levels in breast tissue and urine of 9 women with primary breast cancer using a quantitative liquid chromatography-mass spectrometry method. Results The average levels of estrogens (estrone, 17 beta-estradiol) were significantly higher in breast tissue than in urine. Both the 2 and the 16-hydroxylation pathways were less represented in breast tissue than urine; no components of the 4-hydroxypathway were detected in breast tissue, while 4-hydroxyestrone was measured in urine. However, the 2/16 ratio was similar in urine and breast tissue. Women carrying the variant CYP1B1 genotype (Leu/Val and Val/Val) showed significantly lower overall estrogen metabolite, estrogen, and 16-hydroxylation pathway levels in breast tissue in comparison to women carrying the wild type genotype. No effect of the CYP1B1 polymorphism was observed in urinary metabolites. Conclusions The urinary 2/16 ratio seems a good approximation of the ratio observed in breast tissue. Metabolic genes may have an important role in the estrogen metabolism locally in tissues where the gene is expressed, a role that is not readily observable when urinary measurements are performed.
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