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Occupational exposure to trichloroethylene and risk of non-Hodgkin lymphoma and its major subtypes: a pooled IinterLlymph analysis

Objectives We evaluated the association between occupational exposure to trichloroethylene (TCE) and risk of non-Hodgkin lymphoma (NHL) in a pooled analysis of four international case-control studies. Methods Overall, the pooled study population included 3788 NHL cases and 4279 controls. Risk of NHL and its major subtypes associated with TCE exposure was calculated with unconditional logistic regression and polytomous regression analysis, adjusting by age, gender and study. Results Risk of follicular lymphoma (FL), but not NHL overall or other subtypes, increased by probability (p=0.02) and intensity level (p=0.04), and with the combined analysis of four exposure metrics assumed as independent (p=0.004). After restricting the analysis to the most likely exposed study subjects, risk of NHL overall, FL and chronic lymphocytic leukaemia (CLL) were elevated and increased by duration of exposure (p=0.009, p=0.04 and p=0.01, respectively) and with the combined analysis of duration, frequency and intensity of exposure (p=0.004, p=0.015 and p=0.005, respectively). Although based on small numbers of exposed, risk of all the major NHL subtypes, namely diffuse large B-cell lymphoma, FL and CLL, showed increases in risk ranging 2–3.2-fold in the highest category of exposure intensity. No significant heterogeneity in risk was detected by major NHL subtypes or by study. Conclusions Our pooled analysis apparently supports the hypothesis of an increase in risk of specific NHL subtypes associated with occupational exposure to TCE.

Lymphoma risk in livestock farmers: results of the Epilymph study

We explored the risk of lymphoma and its most prevalent subtypes associated with occupational contact with livestock, and whether risk was modified by age at first contact, in 2,348 incident lymphoma cases and 2,462 controls who participated in the EPILYMPH case–control study. A detailed occupational history was collected in cases and controls, including working in a livestock farm, species of livestock, its approximate number and circumstances of contact. For each disease outcome, and each type of livestock, odds ratios (OR) and their 95% confidence intervals (95% CI) were calculated using unconditional logistic regression, adjusting for age, gender, education and center. Lymphoma risk (all subtypes combined) was not increased amongst those exposed to contact with any livestock (OR = 1.0, 95% CI 0.8–1.2). Overall, we did not observe an association between occupational contact with livestock and risk of lymphoma (all types) and B‐cell lymphoma. The risk of diffuse large B cell lyphoma (DLBCL) was significantly lower amongst subjects who started occupational contact with any species of livestock before or at age 12 (OR = 0.5, 95% CI 0.2–0.9), but not at older ages. A significant heterogeneity in risk of B cell lymphoma by age at first contact was detected for contact with cattle, poultry and swine. Early occupational contact with livestock might be associated with a decrease in risk of B cell lymphoma.

Leukemia in children and youths of the Azuay province, Ecuador: 2000–2010

We mapped leukemia risk among children and youths in the Azuay province, Rio Paute river basin, Ecuador, in 2000–2010, using a Bayesian disease mapping model. We assessed the comprehensiveness of the list of leukemia cases from the Sociedad de Lucha contra el Càncer en el Ecuador (SOLCA) Hospital in Cuenca, the only referral center for oncology in the whole Rio Paute area, by comparison to the Quito cancer registry. Risk of leukemia did not vary significantly by canton within the Azuay province. However, a moderate increase in risk of borderline statistical significance was observed in the city of Cuenca and particularly among males in a heavily industrialized parish, who had an almost eight-fold excess (95% CI 3.03, 20.39, p = 0.01) of AML. Analytical studies are warranted to properly address specific etiological factor of leukemia among children and youths of the Azuay province of Ecuador.

N-acetyltransferase polymorphisms are associated with risk of lymphoma subtypes

Genes encoding for arylamine N‐acetyltransferase 1 and 2 (NAT1 and NAT2) have been investigated with alternate findings in relation to risk of non‐Hodgkin lymphoma (NHL). We tested functional haplotype‐based NAT1 and NAT2 gene polymorphisms in relation to risk of lymphoma overall and its major B cell subtypes, diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukaemia (CLL). We used allele specific primers and multiplex PCR to detect NAT1 and NAT2 haplotypes in 248 patients with incident lymphoma and 208 population controls. We inferred the NAT1 rapid and slow acetylator and the NAT2 rapid, intermediate or slow acetylator phenotype, based on published functional data on the respective genotypes. Odds ratios and 95% confidence intervals (95% CIs) for lymphoma, B‐NHL, DLBCL, FL, CLL, and other B‐NHL combined associated with the inferred rapid NAT1 acetylator and with the intermediate and slow NAT2 acetylator phenotypes were estimated with unconditional and polytomous logistic regression analysis, adjusting for age, gender and education. NAT1 rapid acetylators showed a 2.8‐fold excess risk (95% CI 1.5–5.2) for lymphoma (all subtypes combined). Risk was highest for CLL and FL, with significant heterogeneity detected across subtypes. Risk also increased with decreasing NAT2 acetylating capacity with no heterogeneity detected across B cell lymphoma subtypes. Risks did not vary by gender. Although poor statistical power was a major limitation in our study, larger studies and pooled analyses are warranted to test whether NAT1 and NAT2 gene polymorphisms might modulate risk of specific lymphoma subtypes through the varying metabolic activity of their products. Copyright

0272 Risk of lymphoma and occupational exposure to organic dust

Objectives A medical history of allergy, and particularly asthma, has been associated with an inverse risk of non-Hodgkin’s lymphoma (NHL). As occupational exposure to specific organic dusts is a risk factor for asthma, we explored risk of lymphoma and its major subtypes in relation to organic dusts. Method In 1999–2004, 324 incident lymphoma cases and 464 population controls, frequency matched to cases by age and gender, were recruited among adult residents in Sardinia, Italy. Expert industrial hygienists assessed exposure to organic dust overall, and specific organic dusts. The odds ratio (OR) for lymphoma (all types) and its major subtypes, and its 95% confidence interval, was calculated using unconditional logistic regression. Results Exposure to organic dust in general was inversely associated with risk of lymphoma (all types) (OR = 0.7, 95% CI 0.4–1.2), with a declining trend by duration and level of exposure. The inverse association was apparently more pronounced for exposure to flour dust and wood dust, but not to natural or artificial textile fibres. A consistent inverse risk was observed for B-cell lymphoma (OR = 0.6, 95% CI 0.3–1.0), and it was likewise for its major subtypes, namely diffuse large cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukaemia (CLL). Age <= 18 at first exposure conveyed a further decrease in lymphoma risk (OR = 0.5, 95% CI 0.2–1.2). Conclusions Although with interpretative limitations due to the small study size, our results suggest that exposure to flour dust and wood dust might contribute a reduction in risk of malignant lymphoma.

Do matrix metalloproteinase-1 and glucose-6-phosphate dehydrogenase gene polymorphisms interact in promoting lymphoma development?

MMP9 in favoring local invasion and growth of the tumor [13], is also relevant to NHL susceptibility and progression. The MMP1 gene is located in chromosome region 11q22.3, which is amplified in many solid tumors; a single guanine insertion polymorphism (2G) at  1607 bp in the MMP1 promoter region is associated with an increase in MMP1 transcription and local expression of MMP1 [6]. The 2G insertion at MMP1  1607 has also been related to neoplasia susceptibility and invasiveness [13–15]. Therefore, we hypothesized that the 1G allele of the  1607 promoter polymorphism in MMP1, being associated with lower MMP1 expression, might contribute to less proneness to develop NHL, and that such a protective effect might be reinforced by co-occurrence with the G6PD deficient phenotype, due to the impairment in fibroblast metabolic activity and the nitric oxide synthase (NOS) and ROS release associated with the condition. In turn, NOS and ROS could lead to reduced proliferation or induce apoptosis in potentially carcinogenic cells, but could also initiate tumorigenesis via direct DNA damage [16]. We preliminarily tested the hypothesis in 154 male cases of lymphoma, identified in 1998–2004 in two hematology units in Sardinia, Italy, and 182 male population controls, frequency matched to cases by residence area and 5-year age-group. The lymphoma histotypes in our case series were chronic lymphocytic leukemia (CLL; n  36, 23.4%), diffuse large B-cell lymphoma (DLBCL; n  32, 20.8%), follicular lymphoma (FL; n  16, 10.4%), multiple myeloma (MM; n  12, 7.8%), T cell lymphomas (TCL; n  5, 3.2%), Hodgkin lymphoma (HL; n  8, 5.2%) and other rarer B-cell subtypes and NHL of unspecified cell type (n  45; 29.2%). Females were excluded because of the rarity of the homozygotes for the X-linked G6PD deficient variants. Ethical clearance for the overall project, including this preliminary study, was provided by the Ethics Committee of Cagliari University. All subjects provided informed consent before participating in the study. The authors complied with the Declaration

Lymphoma risk among animal breeders

Objectives Occupational contact with breeding animals might be implicated in lymphoma aetiology. Methods In 1998–2003, 2337 incident lymphoma cases and 2434 controls participated in the EPILYMPH case-control study in six European countries. A detailed occupational history was collected in cases and controls, including species of breeding animals, their approximate number, and circumstances of contact. We conducted a preliminary analysis on ever exposed to contact with breeding animals, and we stratified the analysis by age at first exposure, whether before or after 12. The OR and its 95% CI was calculated with unconditional logistic regression for all lymphomas, and its major subtypes, adjusting by age, gender, and education. Results Lymphoma risk (all subtypes combined) did not increase among those exposed to contact with breeding animals (OR = 1.0, 95% CI 0.8 to 1.2). Risk of DLBCL was significantly lower among subjects employed in poultry farms (OR = 0.6, 95% CI 0.4 to 1.0). This inverse association was observed among subjects who started exposure before or at age 12 (OR = 0.5, 95% CI 0.2 to 1.1), but not later. Conclusions Early occupational contact with poultry might be associated with a decrease in risk of specific lymphoma subtypes.

Risk of specific lymphoma subtypes is associated to polymorphism in genes implicated in the metabolism of workplace carcinogens

Objectives Exploring lymphoma risk associated with metabolic gene polymorphisms might provide clues on the role of gene-environment interactions in lymphomagenesis. Methods We assessed polymorphisms in genes encoding for the metabolic enzymes CYP1A2, CYP2E1, GSTM1, GSTT1, NAT1, NAT2, NQ01, and PON1 in 255 incident lymphoma cases and 204 population controls. The OR for lymphoma overall, B lymphoma, and the diffuse large B cell lymphoma (DLBCL) and chronic lymphocytic leukaemia (CLL) subtypes, associated to the less frequent allele was calculated along with the respective 95% CI, adjusting by age and gender. Results GSTT1 gene polymorphism significantly increased risk of DLBCL (OR = 5.0, IC 95% 3.0 to 8.3). An excess risk of DLBCL was also related to polymorphisms in the CYP1A2, PON1, NAT1 and NAT2genes. CLL risk was reduced in relation to CYP1A2 polymorphisms, increased in relation to GSTM1 deletion, and strongly associated with NAT1, and NAT2 mutant haplotypes. Conclusions Caution is recommended in interpreting the high risks in our study, due its small size. However, our results suggest that polymorphisms in genes encoding for the metabolic enzymes might affect risk of specific lymphoma subtypes associated with exposure to workplace carcinogens.