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  • 1
    Keywords: CANCER ; LUNG ; EMPHYSEMA ; FOLLOW-UP ; lung cancer ; LUNG-CANCER ; NETWORKS ; DEATH ; DISEASE ; DNA adducts ; EXPOSURE ; RISK ; GENES ; TIME ; DNA ; AIR-POLLUTION ; ASSOCIATION ; POLYMORPHISMS ; AGE ; REPAIR ; smoking ; leukemia ; bladder cancer ; BLADDER-CANCER ; cancer risk ; DAMAGE ; POLYCYCLIC AROMATIC-HYDROCARBONS ; DNA-DAMAGE ; RECRUITMENT ; ADDUCTS ; case-control studies ; EPIC ; nutrition ; QUESTIONNAIRE ; WHITE BLOOD-CELLS ; DNA-ADDUCTS ; case-control study ; DETERMINANTS ; monitoring ; GSTM1 ; LEVEL ; ADDUCT ; case control studies ; INTERVAL ; DNA damage ; DNA ADDUCT ; ABILITY ; GENDER ; OUTDOOR AIR-POLLUTION ; OZONE
    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 (32)p 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), 0.88-3.931 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 (O-3) 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 O-3 indicates a possible role for photochemical smog in determining DNA damage
    Type of Publication: Journal article published
    PubMed ID: 16140979
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  • 2
    Keywords: CANCER ; Germany ; LUNG ; FOLLOW-UP ; INFORMATION ; lung cancer ; LUNG-CANCER ; COHORT ; cohort study ; EPIDEMIOLOGY ; EXPOSURE ; MORTALITY ; occupation ; POPULATION ; RISK ; RISKS ; REDUCTION ; RISK-FACTORS ; ASSOCIATION ; HUMANS ; WOMEN ; MEN ; risk factors ; smoking ; COUNTRIES ; cancer risk ; POPULATIONS ; DIET ; VALIDITY ; EPIC ; nutrition ; SMOKERS ; RELATIVE RISK ; exercise ; physical activity ; REGRESSION ; ASSOCIATIONS ; PHYSICAL-ACTIVITY ; INTERVAL ; SUBTYPES ; prospective ; UNIT ; RISK-FACTOR ; CANCER-RISK ; sports ; occupations ; ACTIVITY QUESTIONNAIRE
    Abstract: Research conducted predominantly in male populations on physical activity and lung cancer has yielded inconsistent results. We examined this relationship among 416,277 men and women from the European Prospective Investigation into Cancer and Nutrition (EPIC). Detailed information on recent recreational, household and occupational physical activity, smoking habits and diet was assessed at baseline between 1992 and 2000. Relative risks (RR) were estimated using Cox regression. During 6.3 years of follow-up we identified 607 men and 476 women with incident lung cancer. We did not observe an inverse association between recent occupational, recreational or household physical activity and lung cancer risk in either males or females. However, we found some reduction in lung cancer risk associated with sports in males (adjusted RR = 0.71; 95% confidence interval 0.50-0.98; highest tertile vs. inactive group), cycling (RR = 0.73; 0.54-0.99) in females and non-occupational vigorous physical activity. For occupational physical activity, lung cancer risk was increased for unemployed men (adjusted RR = 1.57; 1.20-2.05) and men with standing occupations (RR = 1.35; 1.02-1.79) compared with sitting professions. There was no evidence of heterogeneity of physical activity associations across countries, or across any of the considered cofactors. For some histologic subtypes suggestive sex-specific reductions, limited by subgroup sizes, were observed, especially with vigorous physical activity. In total, our study shows no consistent protective associations of physical activity with lung cancer risk. It can be assumed that the elevated risks found for occupational physical activity are not produced mechanistically by physical activity itself but rather reflect exposure to occupation-related lung cancer risk factors. (c) 2006 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 16894558
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  • 3
    Keywords: CANCER ; CELLS ; CELL ; Germany ; MODEL ; MODELS ; FOLLOW-UP ; SYSTEM ; cohort study ; DISEASE ; DISEASES ; EPIDEMIOLOGY ; RISK ; RISK-FACTORS ; ASSOCIATION ; NO ; LYMPHOMA ; HEALTH ; WOMEN ; etiology ; risk factors ; DIETARY ; UNITED-STATES ; ALCOHOL-CONSUMPTION ; CONSUMPTION ; FRUIT ; nutrition ; VEGETABLES ; CALIBRATION ; B-CELL LYMPHOMA ; MULTIPLE-MYELOMA ; NON-HODGKINS-LYMPHOMA ; ONCOLOGY ; DIETARY FACTORS ; ASSOCIATIONS ; IMMUNE-SYSTEM ; non-Hodgkin lymphoma ; INTERVAL ; FRUITS ; methods ; function ; prospective ; prospective study ; RISK-FACTOR ; HODGKIN LYMPHOMA ; B-CELL ; N-NITROSO COMPOUNDS ; DRINKING-WATER NITRATE
    Abstract: Introduction Lymphomas are a heterogeneous group of malignant diseases of cells of the immune system. The best-established risk factors are related to dys-regulation of immune function, and evidence suggests that factors such as dietary or lifestyle habits may be involved in the etiology. Material and methods In the European Prospective Investigation into Cancer and Nutrition (EPIC), 849 lymphoma cases were identified in a median follow-up period of 6.4 years. Fruit and vegetable consumption was estimated from validated dietary questionnaires. Cox proportional hazard models were used to examine the association between fruit and vegetable intake with the risk of lymphomas overall and subentities. Results There was no overall association between total fruit and vegetable consumption and risk of lymphoma [hazard ratio (HR) = 0.95, 95% confidence interval (CI) 0.78-1.15 comparing highest with lowest quartile]. However, the risk of diffuse large B-cell lymphomas (DLBCL) tended to be lower in participants with a high intake of total vegetables (HR = 0.49, 95% CI 0.23-1.02). Conclusion In this large prospective study, an inverse associations between fruit and vegetable consumption and risk of lymphomas overall could not be confirmed. Associations with lymphoma subentities such as DLBCL warrant further investigation
    Type of Publication: Journal article published
    PubMed ID: 17443415
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  • 4
    Keywords: CANCER ; LUNG ; PATHWAY ; PATHWAYS ; PHASE-I ; lung cancer ; LUNG-CANCER ; COHORT ; RISK ; ENZYMES ; GENE ; GENES ; PATIENT ; RISK-FACTORS ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; SUSCEPTIBILITY ; VARIANTS ; BREAST-CANCER ; DELETION ; NO ; STRESS ; AGE ; SNP ; smoking ; leukemia ; ACUTE LYMPHOBLASTIC-LEUKEMIA ; bladder cancer ; BLADDER-CANCER ; cancer risk ; gene-environment interaction ; INVOLVEMENT ; case-control studies ; TOBACCO ; OXIDATIVE STRESS ; European Prospective Investigation into Cancer and Nutrition ; nutrition ; glutathione-S-transferase ; DNA-ADDUCTS ; SINGLE ; ONCOLOGY ; case control study ; case-control study ; ASSOCIATIONS ; PATTERN ; VARIANT ; ALLELE ; SINGLE NUCLEOTIDE POLYMORPHISMS ; SNPs ; interaction ; GSTM1 ; METHYLENETETRAHYDROFOLATE REDUCTASE ; MTHFR ; ALLELES ; case control studies ; ENVIRONMENTAL TOBACCO-SMOKE ; INTERVAL ; ENZYME ; methods ; PHASE ; single-nucleotide ; pooled analysis ; prospective ; CANDIDATE ; NEVER SMOKERS ; CANCERS ; CANCER-RISK ; Phase I ; SET ; case control ; METABOLIC PATHWAYS ; GENETIC-SUSCEPTIBILITY ; nonsmokers ; METHYLENE-TETRAHYDROFOLATE REDUCTASE ; metabolic genes ; NULL-GENOTYPE
    Abstract: Background: We chose a set of candidate single nucleotide polymorphisms (SNPs) to investigate gene-environment interactions in three types of cancer that have been related to air pollution (lung, bladder and myeloid leukemia). Patients and methods: The study has been conducted as a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (409 cancer cases and 757 matched controls). We included never and ex-smokers. SNPs were in genes involved in oxidative stress, phase I metabolizing genes, phase 11 metabolizing genes and methylenetetrahydrofolate reductase (MTHFR). Results: The most notable findings are: GSTM1 deletion and bladder cancer risk [odds ratio (OR) = 1.60; 95% confidence interval 1.00-2.56]; CYP1A1 and leukemia (2.22, 1.33-3.70; heterozygotes); CYP1B1 and leukemia (0.47, 0.27-0.84; homozygotes); MnSOD and leukemia (1.91, 1.08-3.38; homozygotes) and NQO1 and lung cancer (8.03, 1.73-37.3; homozygotes). Other statistically significant associations were found in subgroups defined by smoking habits (never or ex-smokers), environmental tobacco smoke or gender, with no obvious pattern. When gene variants were organized according to the three main pathways, the emerging picture was of a strong involvement of combined phase I enzymes in leukemia, with an OR of 5 (1.63-15.4) for those having three or more variant alleles. The association was considerably stronger for leukemias arising before the age of 55
    Type of Publication: Journal article published
    PubMed ID: 17496311
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  • 5
    Keywords: CANCER ; CELLS ; AGENTS ; CELL ; MODEL ; MODELS ; neoplasms ; FOLLOW-UP ; SYSTEM ; COHORT ; cohort study ; EPIDEMIOLOGY ; HISTORY ; incidence ; RISK ; INFECTION ; MECHANISM ; primary ; RISK-FACTORS ; mechanisms ; T cell ; T-CELL ; ASSOCIATION ; DISORDER ; SUSCEPTIBILITY ; NO ; LYMPHOMA ; CARE ; DESIGN ; PLASMA ; AGE ; WOMEN ; etiology ; MEN ; risk factors ; leukemia ; Jun ; diabetes ; ABNORMALITIES ; INFECTIONS ; EPIC ; nutrition ; immunosuppression ; non-hodgkin's lymphoma ; CHRONIC LYMPHOCYTIC-LEUKEMIA ; MULTIPLE-MYELOMA ; VIRAL-INFECTION ; insulin ; MELLITUS ; AGENT ; AUTOIMMUNITY ; multiple myeloma ; DISORDERS ; MEDICAL HISTORY ; INCREASE ; T-CELL LYMPHOMA ; prospective studies ; methods ; SUBTYPES ; metabolic syndrome ; BODY-MASS INDEX ; prospective ; prospective study ; RISK-FACTOR ; CANCERS ; B-CELL ; ENGLAND ; ENVIRONMENTAL-FACTORS ; host ; INCREASES ; viral ; European Prospective Investigation into Cancer ; non-Hodgkin ; neoplasm ; INTERLEUKIN-6 GENE
    Abstract: Background Non-Hodgkin's lymphomas are a heterogeneous group of neoplasms arising from the lymphopoietic system including a wide range of subtypes of either B-cell or T-cell lymphomas. The few established risk factors for the development of these neoplasms include viral infections and immunological abnormalities, but their etiology remains largely unknown. Evidence suggests that certain medical conditions may be linked, through immunosuppression, to the risk of non-Hodgkin's lymphoma. Multiple myeloma is a neoplasm of plasma cells that accounts for approximately 15% of lymphopoietic cancers. Increases in the incidence of non-Hodgkin's lymphoma and multiple myeloma in the past implicate environmental factors as potential causal agents. Design and Methods In the European Prospective Investigation into Cancer and Nutrition (EPIC), 1,213 histologically confirmed incident cases of non-Hodgkin's lymphoma and multiple myeloma (594 men; 619 women) were identified during a follow-up of 8.5 years. Cox proportional hazard models were used to explore the association between self-reported diabetes, diagnosed after 30 years of age, and the risk of non-Hodgkin's lymphoma overall and multiple myeloma and various lymphoma subtypes. Results We found no association between a personal history of diabetes and the risk of non-Hodgkin's lymphoma overall in men (HR: 1.28, 95% CI: 0.89-1.84), in women (HR: 0.71, 95% CI: 0.41-1.24), or in men and women combined (HR: 1.09, 95% CI: 0.80-1.47). Among the B-non-Hodgkin's lymphoma subtypes, we observed a statistically significant increased risk of B-cell chronic lymphocytic leukemia (HR: 2.0, 95% CI: 1.04-3.86) in men, but not in women (HR: 1.07, 95% CI: 0.33-3.43). Conclusions This prospective study did not provide evidence for a role of self-reported diabetes in the etiology of non-Hodgkin's lymphoma overall or multiple myeloma. We found an increased risk of B-cell chronic lymphocytic leukemia among men with diabetes, but not among women. We hypothesize that diabetes may not play a causal role in the etiology of B-cell chronic lymphocytic leukemia, though the underlying pathogenic mechanisms of both disorders may include shared genetic, host and/or environmental susceptibility factors
    Type of Publication: Journal article published
    PubMed ID: 18443270
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  • 6
    Keywords: CANCER ; BLOOD ; LUNG ; FOLLOW-UP ; lung cancer ; LUNG-CANCER ; DNA adducts ; EXPOSURE ; RISK ; SAMPLE ; SAMPLES ; DNA ; CARCINOGENESIS ; AIR-POLLUTION ; BIOMARKERS ; ASSOCIATION ; NO ; HUMANS ; DIFFERENCE ; REPAIR ; meta-analysis ; BLADDER ; bladder cancer ; BLADDER-CANCER ; cancer risk ; DAMAGE ; LYMPHOCYTES ; DNA-DAMAGE ; ADDUCTS ; CARCINOGENS ; case-control studies ; HEALTHY ; SMOKERS ; WHITE BLOOD-CELLS ; ALVEOLAR MACROPHAGES ; DNA-ADDUCTS ; ONCOLOGY ; case-control study ; INCREASE ; CARCINOGEN ; prospective studies ; LIFE ; METAANALYSIS ; LEVEL ; biomarker ; analysis ; DNA damage ; pooled analysis ; prospective ; prospective study ; ONSET ; COMPOUND ; CANCERS ; CANCER-RISK ; ENGLAND ; PREDICT ; POOLED-ANALYSIS ; HEAVY SMOKERS
    Abstract: Bulky DNA adducts are biomarkers of exposure to aromatic compounds and of the ability of the individual to metabolically activate carcinogens and to repair DNA damage. Their ability to predict cancer onset is uncertain. We have performed a pooled analysis of three prospective studies on cancer risk in which bulky DNA adducts have been measured in blood samples collected from healthy subjects (N = 1947; average follow-up 51-137 months). In addition, we have performed a meta-analysis by identifying all articles on the same subject published up to the end of 2006, including case-control studies. In the pooled analysis, a weakly statistically significant increase in the risk of lung cancer was apparent (14% per unit standard deviation change in adduct levels, 95% confidence interval 1-28%; using the weighted mean difference method, 0.15 SD, units higher adducts in cases than in controls). The association was evident only in current smokers and was absent in former smokers. Also the meta-analysis, which included both lung and bladder cancers, showed a statistically significant association in current smokers, whereas the results in never smokers were equivocal; in former smokers, no association was detected. The results of our pooled and meta-analyses suggest that bulky DNA adducts are associated with lung cancer arising in current smokers after a follow-up of several years
    Type of Publication: Journal article published
    PubMed ID: 18343884
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  • 7
    Keywords: CANCER ; LUNG ; LUNG-CANCER ; DISEASE ; EPIDEMIOLOGY ; RISK ; GENE ; GENES ; GENETIC POLYMORPHISMS ; ASSOCIATION ; polymorphism ; HEALTH ; smoking ; SQUAMOUS-CELL CARCINOMA ; case-control studies ; lung neoplasms ; glutathione-S-transferase ; case-control study ; WORLDWIDE ; review ; METAANALYSIS ; GENOTYPE ; CHINESE POPULATION ; PUBLICATION BIAS ; DNA ADDUCT LEVELS ; NULL-GENOTYPE ; Asian continental ancestry group ; glutathione S-transferase pi ; GSTP1 ; HONG-KONG ; P1 POLYMORPHISMS ; PI-GENE
    Abstract: Lung cancer is the most common cancer worldwide. Polymorphisms in genes associated with carcinogen metabolism may modulate risk of disease. Glutathione S-transferase pi (GSTP1) detoxifies polycyclic aromatic hydrocarbons found in cigarette smoke and is the most highly expressed glutathione S-transferase in lung tissue. A polymorphism in the GSTP1 gene, an A-to-G transition in exon 5 (Ile105Val, 313A -〉 313G), results in lower activity among individuals who carry the valine allele. The authors present a meta- and a pooled analysis of case-control studies that examined the association between this polymorphism in GSTP1 and lung cancer risk (27 studies, 8,322 cases and 8,844 controls and 15 studies, 4,282 cases and 5,032 controls, respectively). Overall, the meta-analysis found no significant association between lung cancer risk and the GSTP1 exon 5 polymorphism. In the pooled analysis, there was an overall association (odds ratio = 1.11, 95% confidence interval: 1.03, 1.21) between lung cancer and carriage of the GSTP1 Val/Val or Ile/Val genotype compared with those carrying the Ile/Ile genotype. Increased risk varied by histologic type in Asians. There appears to be evidence for interaction between amount of smoking, the GSTP1 exon 5 polymorphism, and risk of lung cancer in whites
    Type of Publication: Journal article published
    PubMed ID: 19240225
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  • 8
    Keywords: CANCER ; CELLS ; BLOOD ; LUNG ; lung cancer ; LUNG-CANCER ; RISK ; BIOMARKERS ; ASSOCIATION ; HEALTH ; EPIC ; nutrition ; molecular epidemiology ; physical activity ; PHYSICAL-ACTIVITY ; biomarker ; BODY-MASS INDEX ; prospective ; NEVER SMOKERS ; BLOOD GLUTATHIONE CONCENTRATIONS ; BULKY DNA-ADDUCTS ; EX-SMOKERS ; FORMER SMOKERS ; LIFE HABITS ; SMOKING-RELATED DISEASE
    Abstract: The association between physical activity, potential intermediate biomarkers and lung cancer risk was investigated in a study of 230 cases and 648 controls nested within the European Prospective Investigation of Cancer and Nutrition. Data on white blood cell aromatic-DNA adducts by 〈SU32〈/SUP-post-labelling and glutathione (GSH) in red blood cells were available from a subset of cases and controls. Compared with the first quartile, the fourth quartile of recreational physical activity was associated with a lower lung cancer risk (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.35-0.90), higher GSH levels (+1.87 mu mol GSH g〈SU-1〈/SU haemoglobin, p = 0.04) but not with the presence of high levels of adducts (OR 1.05, 95% CI 0.38-2.86). Despite being associated with recreational physical activity, in these small-scale pilot analyses GSH levels were not associated with lung cancer risk (OR 0.95, 95% CI 0.84-1.07 per unit increase in GSH levels). Household and occupational activity was not associated with lung cancer risk or biomarker levels.〈/
    Type of Publication: Journal article published
    PubMed ID: 20050820
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  • 9
    Keywords: CANCER ; RISK ; RECRUITMENT ; nutrition ; N-NITROSO COMPOUNDS ; Epidemiologic studies
    Abstract: Background: Previous epidemiologic studies found inconsistent results for the association between red meat intake, nitrosamines [NDMA: N-nitrosodimethylamine, and ENOC (endogenous nitroso compounds)], and the risk of bladder cancer. We investigated the association between red meat consumption, dietary nitrosamines, and heme iron and the risk of bladder cancer among participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: Data on food consumption and complete follow-up for cancer occurrence were available for a total of 481,419 participants, recruited in 10 European countries. Estimates of HRs were obtained by proportional hazard models, stratified by age at recruitment, gender, and study center and adjusted for total energy intake, smoking status, lifetime intensity of smoking, duration of smoking, educational level, and BMI. Results: After a mean follow-up of 8.7 years, 1,001 participants were diagnosed with bladder cancer. We found no overall association between intake of red meat (log(2) HR: 1.06; 95% CI: 0.99-1.13), nitrosamines (log(2) HR: 1.09; 95% CI: 0.92-1.30 and HR: 0.98; 95% CI: 0.92-1.05 for ENOC and NDMA, respectively) or heme iron (log(2) HR: 1.05; 95 CI: 0.99-1.12) and bladder cancer risk. The associations did not vary by sex, high-versus low-risk bladder cancers, smoking status, or occupation (high vs. low risk). Conclusions: Our findings do not support an effect of red meat intake, nitrosamines (endogenous or exogenous), or heme iron intake on bladder cancer risk.
    Type of Publication: Journal article published
    PubMed ID: 21239687
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  • 10
    Keywords: CANCER ; MODEL ; cohort study ; DESIGN ; OBESITY ; UNITED-STATES ; CHRONIC LYMPHOCYTIC-LEUKEMIA ; MULTIPLE-MYELOMA ; physical activity ; multiple myeloma ; non-Hodgkin lymphoma ; EPIDEMIOLOGIC EVIDENCE ; BODY-MASS INDEX ; RISK-FACTOR ; HODGKIN LYMPHOMA ; ACTIVITY QUESTIONNAIRE ; NON-HODGKIN-LYMPHOMA ; ANTHROPOMETRIC CHARACTERISTICS ; Lymphocytic leukaemia ; Lymphoid neoplasm
    Abstract: Background: Lymphoid neoplasms are a heterogeneous group of cancers that originate in the lymphatic cells of the immune system. Several risk factors have been identified or suggested, but they all account for only a small proportion of the lymphoid neoplasm incidence. It has been hypothesised that regular exercise may modulate the immune system and thereby reduce the risk of developing the disease. Design and methods: The European Investigation into Cancer and Nutrition (EPIC) cohort consists of 521,457 adults, recruited by 23 centres in 10 European countries. The analytical cohort included 343,756 participants, with 778 non-Hodgkin lymphoma (NHL) cases (376 men and 402 women) and 690 B-cell non-Hodgkin lymphoma (B-NHL) cases (326 men and 364 women). Multivariate Cox regression models were used to calculate hazard ratios (HR) for the association between total, recreational, occupational, and household physical activity and NHL and B-NHL risk, as well as the risk for several B-NHL subtypes. Models were stratified by study centre and age at recruitment and adjusted for various potential confounding factors. Results: We found no evidence of any effect of total physical activity on NHL (adjusted p-trend = 0.76 and 0.30 for men and women, respectively) and B-NHL risk (adjusted p-trend = 0.99 and 0.21 for men and women, respectively) for either men or women. Also no robust results were found for B-NHL subtype analyses among men or women. Conclusions: This study provided no consistent evidence for an association between various physical activity measures and the risk of lymphoid neoplasms or any of the B-NHL subtypes.
    Type of Publication: Journal article published
    PubMed ID: 21159506
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