Lymphoma defines a group of different diseases. This study examined pre-treatment plasma samples from 66 adult patients (aged 20-74) newly diagnosed with any lymphoma subtype, and 96 frequency ...matched population controls. We used gas chromatography-mass spectrometry (GC-MS) to compare the metabolic profile by case/control status and across the major lymphoma subtypes. We conducted univariate and multivariate analyses, and partial least square discriminant analysis (PLS-DA). When compared to the controls, statistically validated models were obtained for diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), multiple myeloma (MM), and Hodgkin lymphoma (HL), but not follicular lymphoma (FL). The metabolomic analysis highlighted interesting differences between lymphoma patients and population controls, allowing the discrimination between pathologic and healthy subjects: Important metabolites, such as hypoxanthine and elaidic acid, were more abundant in all lymphoma subtypes. The small sample size of the individual lymphoma subtypes prevented obtaining PLS-DA validated models, although specific peculiar features of each subtype were observed; for instance, fatty acids were most represented in MM and HL patients, while 2-aminoadipic acid, 2-aminoheptanedioic acid, erythritol, and threitol characterized DLBCL and CLL. Metabolomic analysis was able to highlight interesting differences between lymphoma patients and population controls, allowing the discrimination between pathologic and healthy subjects. Further studies are warranted to understand whether the peculiar metabolic patterns observed might serve as early biomarkers of lymphoma.
The International Agency for Research on Cancer (IARC) recently classified glyphosate, the most used herbicide worldwide, as a probable human carcinogen. We inquired into the association between ...occupational exposure to glyphosate and risk of lymphoma subtypes in a multicenter case-control study conducted in Italy.
The Italian Gene-Environment Interactions in Lymphoma Etiology (ItGxE) study took place in 2011-17 in six Italian centres. Overall, 867 incident lymphoma cases and 774 controls participated in the study. Based on detailed questionnaire information, occupational experts classified duration, confidence, frequency, and intensity of exposure to glyphosate for each study subject. Using unconditional regression analysis, we modelled risk of major lymphoma subtypes associated with exposure to glyphosate adjusted by age, gender, education, and study centre.
Very few study subjects (2.2%) were classified as ever exposed to glyphosate. Risk of follicular lymphoma (FL) was elevated 7-fold in subjects classified as ever exposed to glyphosate with medium-high confidence, 4.5-fold in association with medium-high cumulative exposure level, 12-fold with medium-high exposure intensity, and 6-fold with exposure for 10 days or more per year. Significant upward trends were detected with all the exposure metrics, but duration. The overall p-value for an upward trend with four independent metrics was 1.88 × 10
. There was no association with risk of lymphoma (any subtype), Non Hodgkin Lymphoma, B-cell lymphoma, or the major lymphoma subtypes other than FL.
Our findings provide limited support to the IARC decision to classify glyphosate as Group 2A human carcinogen.
Background. The evidence linking the use of household pesticides and the risk of lymphoma is scanty. Methods. We explored the hypothesis in a population-based case-control study on lymphoma conducted ...in Sardinia, Italy, in 1998–2004, including 325 cases and 465 population controls and data on lifetime frequency, seasonality, and years of use of household insecticides and potential confounders. We calculated the risk of lymphoma (all subtypes) and its major subtypes associated with using household insecticides in three time windows (up to 1978, from 1979–2001, and 2002 onwards) with unconditional logistic regression adjusting by age, sex, education, and occupational exposure to pesticides. Results. Household insecticides did not increase risk of lymphoma (all subtypes), Hodgkin’s lymphoma, B-cell lymphoma, and the major B-cell lymphoma subtypes. The risk of multiple myeloma (MM) but not the other subtypes showed a non-significant upward trend (p = 0.203) with increasing quartiles of days of use in the time window when propoxur was the most popular household insecticide. Conclusions. Our results suggest no association between the household use of insecticides and the risk of lymphoma. Further studies are warranted to confirm or discard an association between MM risk and the use of propoxur.
Objectives This study aimed to estimate the risk of lymphoma and its major subtypes in relation to occupational exposure to specific organic dusts. Methods We explored the association in 1853 cases ...and 1997 controls who participated in the EpiLymph case-control study, conducted in six European countries in 1998-2004. Based on expert assessment of lifetime occupational exposures, we calculated the risk of the major lymphoma subtypes associated with exposure to six specific organic dusts, namely, flour, hardwood, softwood, natural textile, synthetic textile, and leather, and two generic (any types) groups: wood and textile dusts. Risk was predicted with unconditional regression modeling, adjusted by age, gender, study center, and education. Results We observed a 2.1-fold increase in risk of follicular lymphoma associated with ever exposure to leather dust 95% confidence interval (CI) 1.01-4.20. After excluding subjects who ever worked in a farm or had ever been exposed to solvents, risk of B-cell lymphoma was elevated in relation to ever exposure to leather dust odd ratio (OR) 2.2, 95% CI 1.00-4.78, but it was not supported by increasing trends with the exposure metrics. Risk of Hodgkin lymphoma was elevated (OR 2.0, 95% CI 0.95-4.30) for exposure to textile dust, with consistent upward trends by cumulative exposure and three independent exposure metrics combined (P=0.023, and P=0.0068, respectively). Conclusions Future, larger studies might provide further insights into the nature of the association we observed between exposure to textile dust and risk of Hodgkin lymphoma.
Purpose Potential sources of exposure to polycyclic aromatic hydrocarbons (PAHs) and genetic polymorphisms were investigated in relation to their contribution to interindividual variation in baseline ...levels of urinary 1-hydroxypyrene (1-OHP) excretion in subjects without occupational exposure to PAHs. Methods Urinary excretion of 1-OHP was measured in 114 subjects, including 48 women and 66 men. Questionnaire information was collected on possible environmental and individual sources of PAH exposure. A subset of 70 individuals also was evaluated for a single-nucleotide polymorphism (Ex7+295C→T) in the cytochrome P-450 1A2 (CYP1A2) gene, and 61 of these also were evaluated for the glutathione transferase T1 (GSTT1) gene polymorphism. Results 1-OHP values did not show a significant seasonal variability and were unaffected by age; education; body mass index; smoking status, including passive smoking; or the C→T base substitution in position 295 of exon 7 of the CYP1A2 gene. After reciprocal adjustment with logistic regression, living in a heavily trafficked urban area (odds ratio, 4.9; 95% confidence interval, 1.0–24.9), and frequent intake of grilled meat (odds ratio, 6.9; 95% confidence interval, 1.1–43.5) were significant predictors of background urinary 1-OHP levels of 0.50 μg/g creatinine or greater. Elevated risks also were associated with daily alcohol intake greater than 65 g and the nonnull GSTT1 genotype. Conclusion Our study shows that exposure to urban traffic, dietary habits, and the nonnull GSTT1 genotype may contribute to interindividual variation in background levels of 1-OHP urinary excretion in subjects without occupational exposure to PAHs.
Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new ...genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 × 10(-21)), rs2523607 at 6p21.33 (HLA-B; P = 2.40 × 10(-10)), rs79480871 at 2p23.3 (NCOA1; P = 4.23 × 10(-8)) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 × 10(-13) and 3.63 × 10(-11), respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.
Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects ...of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, ..., on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval CI = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (... = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (... = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (... = 0.51, SE =0.18), and bladder and lung (... = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation. (ProQuest: ... denotes formulae/symbols omitted.)
Physical activity is known to convey protection against several cancers. However, results on the risk of lymphoma overall and its subtypes have been inconsistent. The aim of this study was to ...investigate occupational and recreational physical activity in relation to risk of lymphoma subtypes adjusting for established occupational risk factors. We applied standardized tools to assess energy expenditure at work and in recreational physical activities to the questionnaire information on lifetime work and exercise history in 1117 lymphoma cases, including Hodgkin lymphoma, and B-cell (including chronic lymphocytic leukemia, and multiple myeloma) and T-cell non-Hodgkin's lymphoma (NHL) subtypes, and 1207 controls who took part in the multicentre European EpiLymph case-control study. We calculated the risk of lymphoma (all subtypes), B-cell NHL and its most represented subtypes, and Hodgkin's lymphoma (all subtypes) associated with weekly average Metabolic Equivalent of Task (MET-hours/week) and cumulative MET-hours of lifetime recreational, occupational, and total physical activity, with unconditional logistic regression and polytomous regression analysis adjusting by age, centre, sex, education, body mass index, history of farm work and solvent use. We observed an inverse association of occupational, and total physical activity with risk of lymphoma (all subtypes), and B-cell non-Hodgkin's lymphoma among women, and an upward trend in risk of Hodgkin's lymphoma with recreational and total physical activity among men, for which we cannot exclude chance or bias. Our results suggest no effect of overall physical activity on risk of lymphoma and its subtypes.
PDF
