Marc Maynadié

Occupational exposure to solvents and risk of lymphoma subtypes: results from the Epilymph case–control study

Background Several studies have suggested an association between occupational exposure to solvents and lymphoma risk. However, findings are inconsistent and the role of specific chemicals is not known. Objective To investigate the role of occupational exposure to organic solvents in the aetiology of B-cell non-Hodgkins lymphoma (B-NHL) and its major subtypes, as well as Hodgkins lymphoma and T-cell lymphoma. Methods 2348 lymphoma cases and 2462 controls participated in a case–control study in six European countries. A subset of cases were reviewed by a panel of pathologists to ensure diagnostic consistency. Exposure to solvents was assessed by industrial hygienists and occupational experts based on a detailed occupational questionnaire. Results Risk of follicular lymphoma significantly increased with three independent metrics of exposure to benzene, toluene and xylene (BTX) (combined p=4×10−7) and to styrene (p=1×10−5), and chronic lymphocytic leukaemia (CLL) risk increased with exposure to solvents overall (p=4×10−6), BTX (p=5×10−5), gasoline (p=8×10−5) and other solvents (p=2×10−6). Risk of B-NHL for ever exposure to solvents was not elevated (OR=1.1, 95% CI 1.0 to 1.3), and that for CLL and follicular lymphoma was 1.3 (95% CI 1.1 to 1.6) and 1.3 (95% CI 1.0 to 1.7), respectively. Exposure to benzene accounted, at least partially, for the association observed with CLL risk. Hodgkins lymphoma and T-cell lymphoma did not show an association with solvent exposure. Conclusion This analysis of a large European dataset confirms a role of occupational exposure to solvents in the aetiology of B-NHL, and particularly, CLL. It is suggested that benzene is most likely to be implicated, but we cannot exclude the possibility of a role for other solvents in relation to other lymphoma subtypes, such as follicular lymphoma. No association with risk of T-cell lymphoma and Hodgkins lymphoma was shown.

Tobacco smoking, alcohol drinking and Hodgkin's lymphoma: a European multi-centre case-control study (EPILYMPH).

We analysed the effects of tobacco and alcohol in the aetiology of Hodgkins lymphoma (HL), based on 340 cases and 2465 controls enrolled in Spain, France, Italy, Germany, Ireland and Czech Republic, between 1998 and 2004. Current smokers showed a significantly increased odds ratio (OR) of HL of 1.39 (95% confidence interval (CI)=1.04–1.87). Analyses were also conducted separately for subjects younger than 35 years (179 cases) and for older subjects (161 cases). For subjects below age 35, no association was observed between tobacco and HL, whereas for older subjects, ever-smokers experienced a doubled risk of HL as compared to never smokers and the OR of HL for current smoking was 2.35 (95% CI=1.52–3.61), with suggestion of a dose–response relationship. A protective effect of alcohol was observed in both age groups. The OR for ever-regular drinking was 0.58 (95% CI=0.38–0.89) for younger subjects and 0.50 (95% CI=0.34–0.74) for older subjects. There was no evidence of interaction between tobacco and alcohol. Our results are consistent with previous studies, suggesting a protective effect of alcohol on HL. An effect of tobacco was suggested for HL occurring in middle and late age, although this finding might have occurred by chance.

Menstrual and reproductive factors, and hormonal contraception use: associations with non-Hodgkin lymphoma in a pooled analysis of InterLymph case–control studies

BACKGROUNDnThe two most common forms of non-Hodgkin lymphoma (NHL) exhibit different sex ratios: diffuse large B-cell lymphoma (DLBCL) occurs more frequently in men and follicular lymphoma (FL) more frequently in women. Looking among women alone, this pooled analysis explores the relationship between reproductive histories and these cancers.nnnMATERIALS AND METHODSnSelf-reported reproductive histories from 4263 women with NHL and 5971 women without NHL were pooled across 18 case-control studies (1983-2005) from North America, Europe and Japan. Study-specific odd ratios (ORs) and confidence intervals (CIs) were estimated using logistic regression and pooled using random-effects meta-analyses.nnnRESULTSnAssociations with reproductive factors were found for FL rather than NHL overall and DLBCL. In particular, the risk of FL decreased with increasing number of pregnancies (pooled ORtrend=0.88, 95% CI 0.81-0.96). FL was associated with hormonal contraception (pooled OR=1.30, 95% CI 1.04-1.63), and risks were increased when use started after the age of 21, was used for <5 years or stopped for >20 years before diagnosis. DLBCL, on the other hand, was not associated with hormonal contraception (pooled OR=0.87, 95% CI 0.65-1.16).nnnCONCLUSIONSnHormonal contraception is associated with an increased risk of FL but not of DLBCL or NHL overall.

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.

Antibodies against lytic and latent Kaposi's sarcoma-associated herpes virus antigens and lymphoma in the European EpiLymph case-control study.

Background:Kaposis sarcoma-associated herpes virus is associated with primary effusion lymphoma and multicentric Castlemans disease.Methods:Seropositivity to lytic and latent Kaposis sarcoma herpes virus (KSHV) antigens were examined in 2083 lymphomas and 2013 controls from six European countries.Results:Antibodies against KSHV latent and lytic antigens were detectable in 4.5% and 3.4% of controls, respectively, and 3.6% of cases (P>0.05). The KSHV seropositivity was associated with splenic marginal zone lymphoma (SMZL) (odds ratio (OR)=4.11, 95% confidence interval (CI)=1.57–10.83) and multiple myeloma (OR=0.31, 95% CI=0.11–0.85).Conclusion:The KSHV is unlikely to contribute importantly to lymphomagenesis among immunocompetent subjects. However, the observed association with SMZL may underline a chronic antigen mechanism in its aetiology.

Incidence of chronic Philadelphia chromosome negative (Ph−) myeloproliferative disorders in the Côte d'Or area, France, during 1980–99

Dear Sir, We read with interest the recent article of Johansson et al. [1] which described the incidence rates for chronic Philadelphia chromosome negative (Ph)) myeloproliferative disorders (MPD) in the city of Göteborg. Their results showed an increased incidence for essential thrombocythemia (ET), especially for males, whereas no significant modification was noted in the incidence of polycythemia vera (PV) nor idiopathic myelofibrosis (IMF). Interestingly, the size of the population of the Côte d’Or area is similar than the one of the city of Göteborg (473 651 and 506 755 inhabitants in Côte d’Or in 1982 and 1999 respectively; 424 085 and 462 470 in Göteborg in 1983 and 1999 respectively) and this allows comparisons between two European regions. We previously reported the epidemiologic features of PV in a population-based registry between 1980 and 1990 [2]. The overall age-standardized incidence rate, based on the world population was 0.7, close to those frequently reported [3]. We analysed the incidence of Ph) MPD between 1991 and 1999, then we measured the evolution of incidence between the two periods. A total of 301 MPD were registered for the period from 1980 to 1999, including 86 PV, 156 ET and 59 IMF (Table 1). In order to compare our results with those of Johansson, we calculated the incidence based on the European Standard Population, and not on the World Population. In our registry, the incidence of PV in the 1991– 99 period was similar to the one observed in the 1980–90 period; no difference between genders was noted. When compared with the results obtained by Johansson et al., the incidence of PV is much lower in Côte d’Or than the one observed in Göteborg (0.84 vs. 1.97 per 10 inhabitants). It is important to note that the incidence of PV reported in Göteborg is one of the highest published [4]. On the contrary, the incidence rate of ET in our registry was similar to the one described by Johansson et al. (1.43 and 1.55 per 10 inhabitants respectively). We also observed a significant increase in the incidence of ET (P 1⁄4 0.001) for men and women. No change during time was noted for IMF. One explanation of the increased rate of ET is a wider availability of platelet counts in routine examination, and we agree with Johansson’s comments. In conclusion, compared with Johansson’s results, our population-based registered data revealed a lower rate in the incidence of PV but confirmed the increase of incidence of ET over the time period.

Occupational Exposure to Ethylene Oxide and Risk of Lymphoma

Background: Ethylene oxide, a high-volume commodity, is an established human carcinogen, although the relevant epidemiologic evidence is limited. Methods: We explored the association between occupational exposure to ethylene oxide and risk of lymphoma in a case-control study, including 2347 lymphoma cases first diagnosed in 1998–2004 and 2463 controls, from 6 European countries. The diagnosis of lymphoma was based on the 2001 World Health Organization Classification of lymphoma. Occupational exposure to ethylene oxide was retrospectively assessed by industrial hygienists and occupational physicians based on detailed self-reported information. We modeled risk of lymphoma with unconditional logistic regression analysis as a function of various exposure measures, adjusting for age, sex, and participating center. Results: Thirty-one cases and 27 controls (1.2% of the total study population) were defined as ever having been exposed to ethylene oxide (odds ratio = 1.3 [95% confidence interval [CI] = 0.7–2.1]). Lymphoma risk showed a 4.3-fold increase associated with medium-high frequency of exposure to ethylene oxide (95% CI = 1.4–13). Among major subtypes, chronic lymphocytic leukemia was consistently associated with ethylene oxide exposure, related in a dose-response manner to probability, frequency, and duration of exposure, as well as to cumulative exposure and (less definitively) with exposure intensity. Conclusions: Our results add to the evidence that ethylene oxide is a human carcinogen.

Révision de la classification des syndromes myéloprolifératifs selon l’OMS en 2016

Resume L’evolution des classifications des pathologies hematologiques est maintenant reguliere depuis la premiere version de la classification etablie sous l’egide de l’OMS. Les elements de la 3 e version viennent d’etre publies dans diverses revues internationales. Les syndromes myeloproliferatifs (SMP) n’ont pas echappe a cette revision et outre quelques modifications des differents criteres diagnostiques, l’element le plus marquant est certainement l’introduction d’une nouvelle entite, la Myelofibrose Primitive en phase precoce ou prefibrotique, intermediaire entre la Thrombocythemie Essentielle et la Myelofibrose Primitive averee. Cela implique la pratique systematique d’une biopsie medullaire devant toute suspicion de SMP, ce qui devrait modifier un tant soit peu les pratiques.

Épidémiologie des syndromes myéloprolifératifs chroniques

Resume Les neoplasies myeloproliferatives chroniques, comme on doit les appeler maintenant, en dehors de la leucemie myeloide chronique (LMC), ont fait l’objet de nombreux ajustements en termes de classification ce qui explique le peu de donnees disponibles sur leurs caracteristiques epidemiologiques. Cependant leur taux d’incidence standardise sur la population mondiale montre que ce sont des maladies rares avec un chiffre variant de 1,7 pour la thrombocytemie essentielle (TE) a 0,3/100 000 habitants/an pour la myelofibrose primitive (MF). La survie nette a 5 ans est proche de 95% pour la polyglobulie de Vaquez (PV) et la TE mais reste de 55% pour la MF. L’incidence de la LMC est, elle, legerement inferieure a 1 et stable depuis longtemps. En revanche l’arrivee des inhibiteurs de tyrosine kinase a revolutionne le pronostic et la survie nette a 5 ans est de plus de 80%.