Get 20M+ Full-Text Papers For Less Than $1.50/day. Subscribe now for You or Your Team.

Learn More →

Exposure to animals and increased risk of marginal zone B-cell lymphomas of the ocular adnexae

Exposure to animals and increased risk of marginal zone B-cell lymphomas of the ocular adnexae Epidemiology British Journal of Cancer (2012) 106, 966 – 969 & 2012 Cancer Research UK All rights reserved 0007 – 0920/12 www.bjcancer.com Short Communication Exposure to animals and increased risk of marginal zone B-cell lymphomas of the ocular adnexae ,1,3 1,3 2 2 2 2 1 2 1 R Dolcetti , D Serraino , G Dognini , S Govi , R Crocchiolo , P Ghia , E Pasini , M Ponzoni , R Talamini , 1 2 2 P De Paoli , C Doglioni and AJM Ferreri 1 2 Centro di Riferimento Oncologico - IRCCS, National Cancer Institute, 33081, Aviano, Italy; Unit of Lymphoid Malignancies, Department of Onco-Hematology, San Raffaele Scientific Institute, 20132, Milan, Italy BACKGROUND: Ocular adnexal marginal zone B-cell lymphoma (OAMZL) has been associated with Chlamydophila psittaci, an infection that may be transmitted by carrier animals. However, it is still unclear whether exposure to animals affects the risk of OAMZL in comparison with other lymphoma histotypes. We therefore investigated the role of professional and/or domestic exposures to animals in the occurrence of OAMZL, as compared with other types of lymphoma. METHODS: A hospital-based case–control study was carried out on 43 consecutive OAMZL patients (cases) and 87 consecutive patients with nodal non-Hodgkin’s lymphomas (NHLs; controls). Multiple logistic regression (MLR) odds ratios (ORs), and 95% confidence intervals (CIs) were used to estimate the association between exposures to animals and OAMZL risk. RESULTS: A higher proportion of cases reported a lifetime exposure to household animals (79.1% vs 64.4% among controls), with a non-statistical significant MLR-OR of 2.18 (95% CI: 0.85–5.62). The OAMZL cases more frequently reported a history of occupation in breeding and/or slaughtering than controls (34.9% vs 6.9%), with an overall increased risk of 7.69 (95%CI: 2.65–22.34). CONCLUSION: These results indicate that, compared with nodal NHLs, the risk of OAMZL is markedly increased by contact with animals, particularly by occupational exposures. British Journal of Cancer (2012) 106, 966–969. doi:10.1038/bjc.2012.2 www.bjcancer.com Published online 24 January 2012 & 2012 Cancer Research UK Keywords: non-Hodgkin’s lymphomas; ocular adnexal marginal zone B-cell lymphoma epidemiology; animal exposure; Chlamydophila psittaci Non-Hodgkin’s lymphomas (NHLs) constitute a heterogeneous zone B-cell lymphoma (OAMZL)) is the commonest entity, and group of malignancies whose aetiology remains elusive (Blinder it has been strongly associated with Chlamydophila psittaci (Cp) and Fisher, 2008). The incidence of NHLs has risen steadily in infection (Ferreri et al, 2004, 2009). This association has been many countries during the last decades, although this cannot be demonstrated with several detection methods, including different entirely attributable to improved diagnosis or classification PCR protocols, immunohistochemistry, immunofluorescence, and (Adamson et al, 2007; Bosetti et al, 2008). Underlying autoimmu- electronic microscopy (Ponzoni et al, 2008). Importantly, viable Cp nity and exposure to environmental, occupational, or infectious has been in vitro isolated from OAMZL patients (Ferreri et al, 2008). agents have been suggested to increase the risk of NHLs Chlamydophila psittaci is the aetiological agent of psittacosis, a (Guidoboni et al, 2006; Alexander et al, 2007; Blinder and Fisher, human zoonotic disease caused by exposure to infected animals, 2008; Hjalgrim and Engels, 2008; Marcucci and Mele, 2011). mostly birds but also domestic mammals and pets (Beeckman and Several animals may be carriers of lymphomagenic infectious Vanrompay, 2009; Sprague et al, 2009). A previous investigation has agents, and indeed elevated risks have been variably associated suggested that contact with household animals is more common with contacts to livestock (Amadori et al, 1995; Svec et al, 2005; among OAMZL patients than in healthy individuals (Ferreri et al, Tranah et al, 2008), or with occupational exposure to meat 2008). It remains to be clarified, however, whether exposure to (Fritschi et al, 2002; McLean and Pearce, 2004). However, as animals affects the risk of OAMZL in comparison with patients available evidence is inconclusive (Moore et al, 2007), as a likely affected by other types of NHLs. We therefore investigated the role consequence of NHL heterogeneity, subtype-specific aetiological of professional and/or domestic exposures to animals in the research is required. occurrence of OAMZL, as compared with the occurrence of other Ocular adnexal lymphomas represent relatively rare lympho- types of lymphoma. proliferative disorders whose incidence is rising (Moslehi et al, 2006). Extranodal marginal zone B-cell lymphoma (ocular adnexal marginal PATIENTS AND METHODS *Correspondence: Dr R Dolcetti; E-mail: rdolcetti@cro.it A hospital-based, case–control study was conducted at the These authors contributed equally to this work. San Raffaele Scientific Institute, Milan, Northern Italy, after Received 2 August 2011; revised 22 December 2011; accepted 27 approval by the local IRB, between June 2004 and December December 2011; published online 24 January 2012 2009. Data were from 43 consecutive OAMZL patients (the cases; Exposure to animals and risk of lymphoma R Dolcetti et al Table 1 Description of the study population according to Table 2 Association between exposure to animals and diagnosis of socio-demographic characteristics and tumour histology (Italy, 2004– 2009) ocular adnexal lymphoma (Italy, 2004 –2009) Cases Controls Cases Controls MLR-OR (n¼ 43) (n¼ 87) no. (%) no. (%) (95% CI) No. (%) No. (%) P-value History of exposure to domestic animals No 9 (20.9) 31 (35.6) 1 Sex Yes, all 34 (79.1) 56 (64.4) 2.18 (0.85 – 5.62) Female 29 (67.4) 44 (50.6) Cats 20 34 2.29 (0.84 – 6.28) Male 14 (32.6) 43 (49.4) 0.10 Dogs 19 25 3.00 (1.00 – 9.05) Birds 18 26 2.00 (0.67 – 5.97) Age p54 16 (37.2) 23 (26.4) History of occupational exposure to animals 55 – 69 15 (34.9) 32 (36.8) No 28 (65.1) 81 (93.1) 1 X70 12 (27.9) 32 (36.8) 0.40 Yes, all 15 (34.9) 6 (6.9) 7.69 (2.65 – 22.34) Slaughter 12 2 16.65 (3.47 – 80.02) Years of education Breeding 3 4 2.65 (0.53 – 13.17) p5 9 (22) 23 (28.4) 6 – 13 26 (63.4) 51 (63.0) Multiple logistic regression (MLR) odds ratios (ORs) adjusted for sex, age and, when X14 6 (14.6) 7 (8.6) 0.51 appropriate, history of occupational exposure to animals (no/yes). Lymphoma histology Extranodal marginal zone lymphoma 43 (100) — Nodal marginal zone lymphoma — 4 (4.6) Diffuse large B-cell lymphoma — 49 (56.3) Table 3 MLR, ORs, and 95% CIs for developing OAMZL by exposures Follicular lymphoma — 32 (36.8) to animals and histological diagnosis of controls (Italy, 2004– 2009) Small lymphocytic lymphoma — 2 (2.3) a b MLR-OR (95% CI) The sum does not add up to the total because of missing values. All diagnoses were confirmed by central pathology review. DLBCL NHL controls FL NHL controls History of exposure to domestic animals No 1 1 median age: 60.0 years) and 87 consecutive control patients with Yes, all 1.47 (0.47 – 4.54) 1.74 (0.51 – 5.88) nodal NHLs (median age: 65.0 years; Table 1). A standardised and Cats 1.80 (0.53 – 6.06) 1.83 (0.47 – 7.11) validated questionnaire was used to investigate the lifetime history Dogs 1.48 (0.35 – 6.27) 2.91 (0.03 – 11.65) of occupational and domestic exposure to cats, dogs, birds, and History of occupational exposure to animals other pets (all vertebrates included). All cases and controls were No 1 1 HIV-negative, while 31/43 OAMZL cases were Cp-associated, as Yes, all 8.61 (2.09 – 36) 9.26 (1.90 – 45) demonstrated by the presence of Cp DNA in tumour tissues Slaughter 18.18 (2.13 – 142) 13.89 (1.66 – 111) (Ferreri et al, 2004). Multiple logistic regression (MLR), odds Breeding 2.81 (0.37 – 21) 4.76 (0.45 – 50) ratios (ORs), and 95% confidence intervals (CIs) were used to Birds 2.15 (0.47.9.82) 1.48 (0.37 – 5.86) estimate the association between the above-mentioned exposures Abbreviations: CI¼ confidence intervals; DLBCL¼ diffuse large B cell lymphoma; and the occurrence of OAMZL (Breslow and Day, 1980). FL¼ follicular lymphoma; MLR¼ multiple logistic regression; ORs¼ odds ratios; OAMZL¼ ocular adnexal marginal zone B-cell lymphoma. MLR ORs adjusted for sex, age and, when appropriate, history of occupational exposure to animals (no/yes). RESULTS Overall, lifetime exposure to domestic animals was more frequently reported by cases (79.1%) than controls (64.4%), with cases with the 49 controls diagnosed with a diffuse large B-cell a non-statistical significant 2.2-fold increased risk of OAMZL lymphoma (DLBCL), or with the 32 controls diagnosed with a (Table 2). The risk of OAMZL was significantly associated with follicular lymphoma (FL; Table 3). The comparison with both domestic exposure to dogs, with a 3-fold increase (95% control groups confirmed the increased risks in OAMZL patients CI:1.009.05). Conversely, increased, but non-statistically signifi- associated with overall occupational exposure to animals (MLR- cant, ORs emerged with regard to exposure to cats and birds. OR¼ 8.61 and MLR-OR¼ 9.26 for DLBCL and FL, respectively) As compared with 6.9% of controls, 34.9% of cases reported a and with slaughtering in particular (MLR-OR¼ 18.18 and lifetime occupational exposure to animals (MLR-OR:7.69; 95% CI: MLR-OR¼ 13.89 for DLBCL and FL, respectively). No statistically 2.65–22.34). In particular, 27.9% of cases were involved in significant elevated risks were found for breeding or exposures to slaughtering with a MLR-OR of 16.65 (lower 95% CI: 3.47; Table 2). domestic animals (Table 3). These results were confirmed when the analysis was restricted to the 31 Cp-associated OAMZL (data not shown in tables). Lifetime exposure to all types of domestic animals was associated with a DISCUSSION 2.44-fold higher risk of OAMZL (95% CI:0.78–7.57), with non significantly elevated risks for exposure to cats (MLR-OR¼ 3.29) To our knowledge, this is the first epidemiological investigation and/or dogs (MLR-OR¼ 3.15). Significantly elevated MLR-OR suggesting that contact with animals is associated with increased were noted among Cp-positive cases for occupational exposure, risk of OAMZL, even in comparison with other NHL entities. This with a 9-fold increase for all types of exposure (MLR-OR¼ 9.22, association seems to be particularly strong for occupational 95% CI: 2.92–29) and a 21-fold higher risk associated with exposure to animals or their products. Previous studies reported slaughtering (95% CI: 4.21–107; data not shown in tables). a globally increased risk of NHL among individuals exposed to The analysis was also stratified according to the histological livestock, mainly cattle and pigs (Amadori et al, 1995; Svec et al, diagnosis of controls, by separately comparing the 43 OAMZL 2005; Tranah et al, 2008), or working with meat (Fritschi et al, & 2012 Cancer Research UK British Journal of Cancer (2012) 106(5), 966 – 969 Epidemiology Epidemiology Exposure to animals and risk of lymphoma R Dolcetti et al 2002; McLean and Pearce, 2004), although these associations were increased risk for Cp-associated OAMZL for individuals exposed to not confirmed (Holly et al, 1997; Persson and Fredrikson, 1999; dogs, even if these animals are presently not considered the main Dryver et al, 2004; Moore et al, 2007). These inconsistencies may vehicle of Cp transmission to humans. Indeed, Cp infection may be due to the fact that NHLs were considered as a single entity or well be detected in dogs (Fukushi et al, 1985; Sprague et al, 2009), that only the major NHL histotypes were analysed. In this study, even in public areas where contamination by potentially zoonotic the analysis of a relatively large series of NHL of a distinct pathogens seems unlikely (Tarsitano et al, 2010). This picture histotype and arising from the same extra-nodal district allowed is similar to what is emerging for gastric lymphomagenesis the identification of a previously unrecognised association of sustained by Helicobacter strains different from Helicobacter OAMZL with occupational exposure to animals, highlighting a pylori, which originate from contacts with domestic animals markedly increased risk. This was particularly evident for (Haesebrouck et al, 2009). slaughterhouse workers, both overall and when cases were Possible limitations of this study include the relatively under- separately compared with DLBCL controls or FL controls. This sized investigated sample and the fact that the recruitment of cases observation reinforced the notion that working in the meat and controls was hospital-based. Considering the relative rarity of industry entails several potentially hazardous exposures, poten- OAMZL, we were able to collect a series of 43 cases large enough to tially including infectious agents. Available evidence, however, obtain results of statistical significance with substantial increased does not support a pathogenic role for zoonotic viruses, such as risks (i.e., 3-fold or higher after adjustment for potential retroviruses and herpes viruses, specific to beef cattle and chicken confounders). It should be admitted, however, that the relative (Bender et al, 1988; Lee et al, 2005). The associations observed in small number of cases limited the analysis stratified by histological our study were even stronger when the analysis was restricted to types. Although cases and controls were carefully matched for age Cp-positive case, thus pointing to the transmission of Cp infection and sex, a slightly higher fraction of females was included in the as a likely relevant risk factor. case group. This was due to the higher prevalence of OAMZL Our findings also provide novel insights into the still among women (Ferreri et al, 2009). controversial issue of the association between contacts with pets In conclusion, this case–control study indicates that domestic and NHL risk (Holly et al, 1997; Persson and Fredrikson, 1999; or occupational contacts with animals increase the risk to develop Dryver et al, 2004; Tranah et al, 2008). We found a borderline OAMZL. These findings further stimulate new investigations significant increase of OAMZL risk associated with exposure to aimed at identifying the aetiologic agents related to this exposure one or more domestic animals, especially to dogs. Our results may and involved in OAMZL pathogenesis. be consistent with the peculiar pathogenic mechanisms proposed for OAMZL, which likely involve a chronic stimulation by exogenous antigen(s) (Ferreri et al, 2009). In this scenario, contacts ACKNOWLEDGEMENTS with domestic animals may favour the transmission of infectious agents that, under still poorly defined circumstances, may trigger This work was supported by the Associazione Italiana per la and sustain B-cell lymphoproliferation. The further increased risk Ricerca sul Cancro (AIRC; 1031 to RD and 9226 to CD) and of OAMZL detected when only Cp-associated cases were analysed is Fondazione Federica per la Vita. EP is a fellow of the Fondazione consistent with this hypothesis. Intriguingly, we observed an Italiana per la Ricerca sul Cancro (FIRC). REFERENCES Adamson P, Bray F, Costantini AS, Tao MH, Weiderpass E, Roman E conjunctiva and peripheral blood of patients with ocular adnexal (2007) Time trends in the registration of Hodgkin and non-Hodgkin lymphoma: results of a single-center prospective case-control study. lymphomas in Europe. Eur J Cancer 43: 391–401 Int J Cancer 123: 1089–1093 Alexander DD, Mink PJ, Adami HO, Chang ET, Cole P, Mandel JS, Ferreri AJ, Dolcetti R, Magnino S, Doglioni C, Ponzoni M (2009) Trichopoulos D (2007) The non-Hodgkin lymphomas: a review of the Chlamydial infection: the link with ocular adnexal lymphomas. Nat epidemiologic literature. Int J Cancer 120(Suppl 12): 1–39 Rev Clin Oncol 6: 658 –669 Amadori D, Nanni O, Falcini F, Saragoni A, Tison V, Callea A, Scarpi E, Ferreri AJ, Guidoboni M, Ponzoni M, De CC, Dell’Oro S, Fleischhauer K, Ricci M, Riva N, Buiatti E (1995) Chronic lymphocytic leukaemias and Caggiari L, Lettini AA, Dal Cin CE, Ieri R, Freschi M, Villa E, Boiocchi M, non-Hodgkin’s lymphomas by histological type in farming-animal Dolcetti R (2004) Evidence for an association between Chlamydia psittaci breeding workers: a population case-control study based on job titles. and ocular adnexal lymphomas. J Natl Cancer Inst 96: 586–594 Occup Environ Med 52: 374 –379 Fritschi L, Johnson KC, Kliewer EV, Fry R (2002) Animal-related Beeckman DS, Vanrompay DC (2009) Zoonotic Chlamydophila psittaci occupations and the risk of leukemia, myeloma, and non-Hodgkin’s infections from a clinical perspective. Clin Microbiol Infect 15: 11–17 lymphoma in Canada. Cancer Causes Control 13: 563–571 Bender AP, Robison LL, Kashmiri SV, McClain KL, Woods WG, Smithson Fukushi H, Ogawa H, Minamoto N, Hashimoto A, Yagami K, Tamura H, WA, Heyn R, Finlay J, Schuman LM, Renier C (1988) No involvement of Shimakura S, Hirai K (1985) Seroepidemiological surveillance of bovine leukemia virus in childhood acute lymphoblastic leukemia and Chlamydia psittaci in cats and dogs in Japan. Vet Rec 117: 503– 504 non-Hodgkin’s lymphoma. Cancer Res 48: 2919–2922 Guidoboni M, Ferreri AJ, Ponzoni M, Doglioni C, Dolcetti R (2006) Blinder V, Fisher SG (2008) The role of environmental factors in the Infectious agents in mucosa-associated lymphoid tissue-type lympho- etiology of lymphoma. Cancer Invest 26: 306–316 mas: pathogenic role and therapeutic perspectives. Clin Lymphoma Bosetti C, Levi F, Ferlay J, Lucchini F, Negri E, La VC (2008) Incidence and Myeloma 6: 289–300 mortality from non-Hodgkin lymphoma in Europe: the end of an Haesebrouck F, Pasmans F, Flahou B, Chiers K, Baele M, Meyns T, epidemic? Int J Cancer 123: 1917–1923 Decostere A, Ducatelle R (2009) Gastric helicobacters in domestic Breslow NE, Day NE (1980) Statistical Methods in Cancer Research. animals and nonhuman primates and their significance for human Vol. I. The Analysis of Case-control Studies. No. 32ed. IARC Scientific health. Clin Microbiol Rev 22: 202–223 Publications: Lyon, France, pp 192–247 Hjalgrim H, Engels EA (2008) Infectious aetiology of Hodgkin and non- Dryver E, Brandt L, Kauppinen T, Olsson H (2004) Occupational exposures Hodgkin lymphomas: a review of the epidemiological evidence. J Intern and non-Hodgkin’s lymphoma in Southern Sweden. Int J Occup Environ Med 264: 537–548 Health 10: 13–21 Holly EA, Lele C, Bracci P (1997) Non-Hodgkin’s lymphoma in homosexual Ferreri AJ, Dolcetti R, Dognini GP, Malabarba L, Vicari N, Pasini E, men in the San Francisco Bay Area: occupational, chemical, and Ponzoni M, Cangi MG, Pecciarini L, Resti AG, Doglioni C, Rossini S, environmental exposures. J Acquir Immune Defic Syndr Hum Retrovirol Magnino S (2008) Chlamydophila psittaci is viable and infectious in the 15: 223–231 British Journal of Cancer (2012) 106(5), 966 – 969 & 2012 Cancer Research UK Exposure to animals and risk of lymphoma R Dolcetti et al Lee J, Kim Y, Kang CS, Cho DH, Shin DH, Yum YN, Oh JH, Kim SH, Doglioni C (2008) Chlamydia infection and lymphomas: association Hwang MS, Lim CJ, Yang KH, Han K (2005) Investigation of the bovine beyond ocular adnexal lymphomas highlighted by multiple detection leukemia virus proviral DNA in human leukemias and lung cancers in methods. Clin Cancer Res 14: 5794–5800 Korea. J Korean Med Sci 20: 603–606 Sprague LD, Schubert E, Hotzel H, Scharf S, Sachse K (2009) The detection Marcucci F, Mele A (2011) Hepatitis viruses and non-Hodgkin lymphoma: of Chlamydophila psittaci genotype C infection in dogs. Vet J 181: epidemiology, mechanisms of tumorigenesis, and therapeutic opportu- 274–279 nities. Blood 117: 1792–1798 Svec MA, Ward MH, Dosemeci M, Checkoway H, De Roos AJ (2005) McLean D, Pearce N (2004) Cancer among meat industry workers. Scand J Risk of lymphatic or haematopoietic cancer mortality with occupa- Work Environ Health 30: 425–437 tional exposure to animals or the public. Occup Environ Med 62: Moore T, Brennan P, Becker N, de SS, Maynadie M, Foretova L, Cocco P, 726–735 Staines A, Nieters A, Font R, Mannetje A, Benhaim-Luzon V, Boffetta P Tarsitano E, Greco G, Decaro N, Nicassio F, Lucente MS, Buonavoglia C, (2007) Occupational exposure to meat and risk of lymphoma: a Tempesta M (2010) Environmental monitoring and analysis of faecal multicenter case-control study from Europe. Int J Cancer 121: 2761–2766 contamination in an urban setting in the city of Bari (Apulia region, Moslehi R, Devesa SS, Schairer C, Fraumeni Jr JF (2006) Rapidly increasing Italy): health and hygiene implications. Int J Environ Res Public Health 7: incidence of ocular non-hodgkin lymphoma. J Natl Cancer Inst 98: 936–939 3972– 3986 Persson B, Fredrikson M (1999) Some risk factors for non-Hodgkin’s Tranah GJ, Bracci PM, Holly EA (2008) Domestic and farm-animal lymphoma. Int J Occup Med Environ Health 12: 135–142 exposures and risk of non-Hodgkin’s lymphoma in a population-based Ponzoni M, Ferreri AJ, Guidoboni M, Lettini AA, Cangi MG, Pasini E, study in the San Francisco Bay Area. Cancer Epidemiol Biomarkers Prev Sacchi L, Pecciarini L, Grassi S, Dal CE, Stefano R, Magnino S, Dolcetti R, 17: 2382–2387 & 2012 Cancer Research UK British Journal of Cancer (2012) 106(5), 966 – 969 Epidemiology http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Cancer Springer Journals

Exposure to animals and increased risk of marginal zone B-cell lymphomas of the ocular adnexae

Loading next page...
 
/lp/springer-journals/exposure-to-animals-and-increased-risk-of-marginal-zone-b-cell-wQtxpAvXyP

References (97)

Publisher
Springer Journals
Copyright
Copyright © 2012 by The Author(s)
Subject
Biomedicine; Biomedicine, general; Cancer Research; Epidemiology; Molecular Medicine; Oncology; Drug Resistance
ISSN
0007-0920
eISSN
1532-1827
DOI
10.1038/bjc.2012.2
Publisher site
See Article on Publisher Site

Abstract

Epidemiology British Journal of Cancer (2012) 106, 966 – 969 & 2012 Cancer Research UK All rights reserved 0007 – 0920/12 www.bjcancer.com Short Communication Exposure to animals and increased risk of marginal zone B-cell lymphomas of the ocular adnexae ,1,3 1,3 2 2 2 2 1 2 1 R Dolcetti , D Serraino , G Dognini , S Govi , R Crocchiolo , P Ghia , E Pasini , M Ponzoni , R Talamini , 1 2 2 P De Paoli , C Doglioni and AJM Ferreri 1 2 Centro di Riferimento Oncologico - IRCCS, National Cancer Institute, 33081, Aviano, Italy; Unit of Lymphoid Malignancies, Department of Onco-Hematology, San Raffaele Scientific Institute, 20132, Milan, Italy BACKGROUND: Ocular adnexal marginal zone B-cell lymphoma (OAMZL) has been associated with Chlamydophila psittaci, an infection that may be transmitted by carrier animals. However, it is still unclear whether exposure to animals affects the risk of OAMZL in comparison with other lymphoma histotypes. We therefore investigated the role of professional and/or domestic exposures to animals in the occurrence of OAMZL, as compared with other types of lymphoma. METHODS: A hospital-based case–control study was carried out on 43 consecutive OAMZL patients (cases) and 87 consecutive patients with nodal non-Hodgkin’s lymphomas (NHLs; controls). Multiple logistic regression (MLR) odds ratios (ORs), and 95% confidence intervals (CIs) were used to estimate the association between exposures to animals and OAMZL risk. RESULTS: A higher proportion of cases reported a lifetime exposure to household animals (79.1% vs 64.4% among controls), with a non-statistical significant MLR-OR of 2.18 (95% CI: 0.85–5.62). The OAMZL cases more frequently reported a history of occupation in breeding and/or slaughtering than controls (34.9% vs 6.9%), with an overall increased risk of 7.69 (95%CI: 2.65–22.34). CONCLUSION: These results indicate that, compared with nodal NHLs, the risk of OAMZL is markedly increased by contact with animals, particularly by occupational exposures. British Journal of Cancer (2012) 106, 966–969. doi:10.1038/bjc.2012.2 www.bjcancer.com Published online 24 January 2012 & 2012 Cancer Research UK Keywords: non-Hodgkin’s lymphomas; ocular adnexal marginal zone B-cell lymphoma epidemiology; animal exposure; Chlamydophila psittaci Non-Hodgkin’s lymphomas (NHLs) constitute a heterogeneous zone B-cell lymphoma (OAMZL)) is the commonest entity, and group of malignancies whose aetiology remains elusive (Blinder it has been strongly associated with Chlamydophila psittaci (Cp) and Fisher, 2008). The incidence of NHLs has risen steadily in infection (Ferreri et al, 2004, 2009). This association has been many countries during the last decades, although this cannot be demonstrated with several detection methods, including different entirely attributable to improved diagnosis or classification PCR protocols, immunohistochemistry, immunofluorescence, and (Adamson et al, 2007; Bosetti et al, 2008). Underlying autoimmu- electronic microscopy (Ponzoni et al, 2008). Importantly, viable Cp nity and exposure to environmental, occupational, or infectious has been in vitro isolated from OAMZL patients (Ferreri et al, 2008). agents have been suggested to increase the risk of NHLs Chlamydophila psittaci is the aetiological agent of psittacosis, a (Guidoboni et al, 2006; Alexander et al, 2007; Blinder and Fisher, human zoonotic disease caused by exposure to infected animals, 2008; Hjalgrim and Engels, 2008; Marcucci and Mele, 2011). mostly birds but also domestic mammals and pets (Beeckman and Several animals may be carriers of lymphomagenic infectious Vanrompay, 2009; Sprague et al, 2009). A previous investigation has agents, and indeed elevated risks have been variably associated suggested that contact with household animals is more common with contacts to livestock (Amadori et al, 1995; Svec et al, 2005; among OAMZL patients than in healthy individuals (Ferreri et al, Tranah et al, 2008), or with occupational exposure to meat 2008). It remains to be clarified, however, whether exposure to (Fritschi et al, 2002; McLean and Pearce, 2004). However, as animals affects the risk of OAMZL in comparison with patients available evidence is inconclusive (Moore et al, 2007), as a likely affected by other types of NHLs. We therefore investigated the role consequence of NHL heterogeneity, subtype-specific aetiological of professional and/or domestic exposures to animals in the research is required. occurrence of OAMZL, as compared with the occurrence of other Ocular adnexal lymphomas represent relatively rare lympho- types of lymphoma. proliferative disorders whose incidence is rising (Moslehi et al, 2006). Extranodal marginal zone B-cell lymphoma (ocular adnexal marginal PATIENTS AND METHODS *Correspondence: Dr R Dolcetti; E-mail: rdolcetti@cro.it A hospital-based, case–control study was conducted at the These authors contributed equally to this work. San Raffaele Scientific Institute, Milan, Northern Italy, after Received 2 August 2011; revised 22 December 2011; accepted 27 approval by the local IRB, between June 2004 and December December 2011; published online 24 January 2012 2009. Data were from 43 consecutive OAMZL patients (the cases; Exposure to animals and risk of lymphoma R Dolcetti et al Table 1 Description of the study population according to Table 2 Association between exposure to animals and diagnosis of socio-demographic characteristics and tumour histology (Italy, 2004– 2009) ocular adnexal lymphoma (Italy, 2004 –2009) Cases Controls Cases Controls MLR-OR (n¼ 43) (n¼ 87) no. (%) no. (%) (95% CI) No. (%) No. (%) P-value History of exposure to domestic animals No 9 (20.9) 31 (35.6) 1 Sex Yes, all 34 (79.1) 56 (64.4) 2.18 (0.85 – 5.62) Female 29 (67.4) 44 (50.6) Cats 20 34 2.29 (0.84 – 6.28) Male 14 (32.6) 43 (49.4) 0.10 Dogs 19 25 3.00 (1.00 – 9.05) Birds 18 26 2.00 (0.67 – 5.97) Age p54 16 (37.2) 23 (26.4) History of occupational exposure to animals 55 – 69 15 (34.9) 32 (36.8) No 28 (65.1) 81 (93.1) 1 X70 12 (27.9) 32 (36.8) 0.40 Yes, all 15 (34.9) 6 (6.9) 7.69 (2.65 – 22.34) Slaughter 12 2 16.65 (3.47 – 80.02) Years of education Breeding 3 4 2.65 (0.53 – 13.17) p5 9 (22) 23 (28.4) 6 – 13 26 (63.4) 51 (63.0) Multiple logistic regression (MLR) odds ratios (ORs) adjusted for sex, age and, when X14 6 (14.6) 7 (8.6) 0.51 appropriate, history of occupational exposure to animals (no/yes). Lymphoma histology Extranodal marginal zone lymphoma 43 (100) — Nodal marginal zone lymphoma — 4 (4.6) Diffuse large B-cell lymphoma — 49 (56.3) Table 3 MLR, ORs, and 95% CIs for developing OAMZL by exposures Follicular lymphoma — 32 (36.8) to animals and histological diagnosis of controls (Italy, 2004– 2009) Small lymphocytic lymphoma — 2 (2.3) a b MLR-OR (95% CI) The sum does not add up to the total because of missing values. All diagnoses were confirmed by central pathology review. DLBCL NHL controls FL NHL controls History of exposure to domestic animals No 1 1 median age: 60.0 years) and 87 consecutive control patients with Yes, all 1.47 (0.47 – 4.54) 1.74 (0.51 – 5.88) nodal NHLs (median age: 65.0 years; Table 1). A standardised and Cats 1.80 (0.53 – 6.06) 1.83 (0.47 – 7.11) validated questionnaire was used to investigate the lifetime history Dogs 1.48 (0.35 – 6.27) 2.91 (0.03 – 11.65) of occupational and domestic exposure to cats, dogs, birds, and History of occupational exposure to animals other pets (all vertebrates included). All cases and controls were No 1 1 HIV-negative, while 31/43 OAMZL cases were Cp-associated, as Yes, all 8.61 (2.09 – 36) 9.26 (1.90 – 45) demonstrated by the presence of Cp DNA in tumour tissues Slaughter 18.18 (2.13 – 142) 13.89 (1.66 – 111) (Ferreri et al, 2004). Multiple logistic regression (MLR), odds Breeding 2.81 (0.37 – 21) 4.76 (0.45 – 50) ratios (ORs), and 95% confidence intervals (CIs) were used to Birds 2.15 (0.47.9.82) 1.48 (0.37 – 5.86) estimate the association between the above-mentioned exposures Abbreviations: CI¼ confidence intervals; DLBCL¼ diffuse large B cell lymphoma; and the occurrence of OAMZL (Breslow and Day, 1980). FL¼ follicular lymphoma; MLR¼ multiple logistic regression; ORs¼ odds ratios; OAMZL¼ ocular adnexal marginal zone B-cell lymphoma. MLR ORs adjusted for sex, age and, when appropriate, history of occupational exposure to animals (no/yes). RESULTS Overall, lifetime exposure to domestic animals was more frequently reported by cases (79.1%) than controls (64.4%), with cases with the 49 controls diagnosed with a diffuse large B-cell a non-statistical significant 2.2-fold increased risk of OAMZL lymphoma (DLBCL), or with the 32 controls diagnosed with a (Table 2). The risk of OAMZL was significantly associated with follicular lymphoma (FL; Table 3). The comparison with both domestic exposure to dogs, with a 3-fold increase (95% control groups confirmed the increased risks in OAMZL patients CI:1.009.05). Conversely, increased, but non-statistically signifi- associated with overall occupational exposure to animals (MLR- cant, ORs emerged with regard to exposure to cats and birds. OR¼ 8.61 and MLR-OR¼ 9.26 for DLBCL and FL, respectively) As compared with 6.9% of controls, 34.9% of cases reported a and with slaughtering in particular (MLR-OR¼ 18.18 and lifetime occupational exposure to animals (MLR-OR:7.69; 95% CI: MLR-OR¼ 13.89 for DLBCL and FL, respectively). No statistically 2.65–22.34). In particular, 27.9% of cases were involved in significant elevated risks were found for breeding or exposures to slaughtering with a MLR-OR of 16.65 (lower 95% CI: 3.47; Table 2). domestic animals (Table 3). These results were confirmed when the analysis was restricted to the 31 Cp-associated OAMZL (data not shown in tables). Lifetime exposure to all types of domestic animals was associated with a DISCUSSION 2.44-fold higher risk of OAMZL (95% CI:0.78–7.57), with non significantly elevated risks for exposure to cats (MLR-OR¼ 3.29) To our knowledge, this is the first epidemiological investigation and/or dogs (MLR-OR¼ 3.15). Significantly elevated MLR-OR suggesting that contact with animals is associated with increased were noted among Cp-positive cases for occupational exposure, risk of OAMZL, even in comparison with other NHL entities. This with a 9-fold increase for all types of exposure (MLR-OR¼ 9.22, association seems to be particularly strong for occupational 95% CI: 2.92–29) and a 21-fold higher risk associated with exposure to animals or their products. Previous studies reported slaughtering (95% CI: 4.21–107; data not shown in tables). a globally increased risk of NHL among individuals exposed to The analysis was also stratified according to the histological livestock, mainly cattle and pigs (Amadori et al, 1995; Svec et al, diagnosis of controls, by separately comparing the 43 OAMZL 2005; Tranah et al, 2008), or working with meat (Fritschi et al, & 2012 Cancer Research UK British Journal of Cancer (2012) 106(5), 966 – 969 Epidemiology Epidemiology Exposure to animals and risk of lymphoma R Dolcetti et al 2002; McLean and Pearce, 2004), although these associations were increased risk for Cp-associated OAMZL for individuals exposed to not confirmed (Holly et al, 1997; Persson and Fredrikson, 1999; dogs, even if these animals are presently not considered the main Dryver et al, 2004; Moore et al, 2007). These inconsistencies may vehicle of Cp transmission to humans. Indeed, Cp infection may be due to the fact that NHLs were considered as a single entity or well be detected in dogs (Fukushi et al, 1985; Sprague et al, 2009), that only the major NHL histotypes were analysed. In this study, even in public areas where contamination by potentially zoonotic the analysis of a relatively large series of NHL of a distinct pathogens seems unlikely (Tarsitano et al, 2010). This picture histotype and arising from the same extra-nodal district allowed is similar to what is emerging for gastric lymphomagenesis the identification of a previously unrecognised association of sustained by Helicobacter strains different from Helicobacter OAMZL with occupational exposure to animals, highlighting a pylori, which originate from contacts with domestic animals markedly increased risk. This was particularly evident for (Haesebrouck et al, 2009). slaughterhouse workers, both overall and when cases were Possible limitations of this study include the relatively under- separately compared with DLBCL controls or FL controls. This sized investigated sample and the fact that the recruitment of cases observation reinforced the notion that working in the meat and controls was hospital-based. Considering the relative rarity of industry entails several potentially hazardous exposures, poten- OAMZL, we were able to collect a series of 43 cases large enough to tially including infectious agents. Available evidence, however, obtain results of statistical significance with substantial increased does not support a pathogenic role for zoonotic viruses, such as risks (i.e., 3-fold or higher after adjustment for potential retroviruses and herpes viruses, specific to beef cattle and chicken confounders). It should be admitted, however, that the relative (Bender et al, 1988; Lee et al, 2005). The associations observed in small number of cases limited the analysis stratified by histological our study were even stronger when the analysis was restricted to types. Although cases and controls were carefully matched for age Cp-positive case, thus pointing to the transmission of Cp infection and sex, a slightly higher fraction of females was included in the as a likely relevant risk factor. case group. This was due to the higher prevalence of OAMZL Our findings also provide novel insights into the still among women (Ferreri et al, 2009). controversial issue of the association between contacts with pets In conclusion, this case–control study indicates that domestic and NHL risk (Holly et al, 1997; Persson and Fredrikson, 1999; or occupational contacts with animals increase the risk to develop Dryver et al, 2004; Tranah et al, 2008). We found a borderline OAMZL. These findings further stimulate new investigations significant increase of OAMZL risk associated with exposure to aimed at identifying the aetiologic agents related to this exposure one or more domestic animals, especially to dogs. Our results may and involved in OAMZL pathogenesis. be consistent with the peculiar pathogenic mechanisms proposed for OAMZL, which likely involve a chronic stimulation by exogenous antigen(s) (Ferreri et al, 2009). In this scenario, contacts ACKNOWLEDGEMENTS with domestic animals may favour the transmission of infectious agents that, under still poorly defined circumstances, may trigger This work was supported by the Associazione Italiana per la and sustain B-cell lymphoproliferation. The further increased risk Ricerca sul Cancro (AIRC; 1031 to RD and 9226 to CD) and of OAMZL detected when only Cp-associated cases were analysed is Fondazione Federica per la Vita. EP is a fellow of the Fondazione consistent with this hypothesis. Intriguingly, we observed an Italiana per la Ricerca sul Cancro (FIRC). REFERENCES Adamson P, Bray F, Costantini AS, Tao MH, Weiderpass E, Roman E conjunctiva and peripheral blood of patients with ocular adnexal (2007) Time trends in the registration of Hodgkin and non-Hodgkin lymphoma: results of a single-center prospective case-control study. lymphomas in Europe. Eur J Cancer 43: 391–401 Int J Cancer 123: 1089–1093 Alexander DD, Mink PJ, Adami HO, Chang ET, Cole P, Mandel JS, Ferreri AJ, Dolcetti R, Magnino S, Doglioni C, Ponzoni M (2009) Trichopoulos D (2007) The non-Hodgkin lymphomas: a review of the Chlamydial infection: the link with ocular adnexal lymphomas. Nat epidemiologic literature. Int J Cancer 120(Suppl 12): 1–39 Rev Clin Oncol 6: 658 –669 Amadori D, Nanni O, Falcini F, Saragoni A, Tison V, Callea A, Scarpi E, Ferreri AJ, Guidoboni M, Ponzoni M, De CC, Dell’Oro S, Fleischhauer K, Ricci M, Riva N, Buiatti E (1995) Chronic lymphocytic leukaemias and Caggiari L, Lettini AA, Dal Cin CE, Ieri R, Freschi M, Villa E, Boiocchi M, non-Hodgkin’s lymphomas by histological type in farming-animal Dolcetti R (2004) Evidence for an association between Chlamydia psittaci breeding workers: a population case-control study based on job titles. and ocular adnexal lymphomas. J Natl Cancer Inst 96: 586–594 Occup Environ Med 52: 374 –379 Fritschi L, Johnson KC, Kliewer EV, Fry R (2002) Animal-related Beeckman DS, Vanrompay DC (2009) Zoonotic Chlamydophila psittaci occupations and the risk of leukemia, myeloma, and non-Hodgkin’s infections from a clinical perspective. Clin Microbiol Infect 15: 11–17 lymphoma in Canada. Cancer Causes Control 13: 563–571 Bender AP, Robison LL, Kashmiri SV, McClain KL, Woods WG, Smithson Fukushi H, Ogawa H, Minamoto N, Hashimoto A, Yagami K, Tamura H, WA, Heyn R, Finlay J, Schuman LM, Renier C (1988) No involvement of Shimakura S, Hirai K (1985) Seroepidemiological surveillance of bovine leukemia virus in childhood acute lymphoblastic leukemia and Chlamydia psittaci in cats and dogs in Japan. Vet Rec 117: 503– 504 non-Hodgkin’s lymphoma. Cancer Res 48: 2919–2922 Guidoboni M, Ferreri AJ, Ponzoni M, Doglioni C, Dolcetti R (2006) Blinder V, Fisher SG (2008) The role of environmental factors in the Infectious agents in mucosa-associated lymphoid tissue-type lympho- etiology of lymphoma. Cancer Invest 26: 306–316 mas: pathogenic role and therapeutic perspectives. Clin Lymphoma Bosetti C, Levi F, Ferlay J, Lucchini F, Negri E, La VC (2008) Incidence and Myeloma 6: 289–300 mortality from non-Hodgkin lymphoma in Europe: the end of an Haesebrouck F, Pasmans F, Flahou B, Chiers K, Baele M, Meyns T, epidemic? Int J Cancer 123: 1917–1923 Decostere A, Ducatelle R (2009) Gastric helicobacters in domestic Breslow NE, Day NE (1980) Statistical Methods in Cancer Research. animals and nonhuman primates and their significance for human Vol. I. The Analysis of Case-control Studies. No. 32ed. IARC Scientific health. Clin Microbiol Rev 22: 202–223 Publications: Lyon, France, pp 192–247 Hjalgrim H, Engels EA (2008) Infectious aetiology of Hodgkin and non- Dryver E, Brandt L, Kauppinen T, Olsson H (2004) Occupational exposures Hodgkin lymphomas: a review of the epidemiological evidence. J Intern and non-Hodgkin’s lymphoma in Southern Sweden. Int J Occup Environ Med 264: 537–548 Health 10: 13–21 Holly EA, Lele C, Bracci P (1997) Non-Hodgkin’s lymphoma in homosexual Ferreri AJ, Dolcetti R, Dognini GP, Malabarba L, Vicari N, Pasini E, men in the San Francisco Bay Area: occupational, chemical, and Ponzoni M, Cangi MG, Pecciarini L, Resti AG, Doglioni C, Rossini S, environmental exposures. J Acquir Immune Defic Syndr Hum Retrovirol Magnino S (2008) Chlamydophila psittaci is viable and infectious in the 15: 223–231 British Journal of Cancer (2012) 106(5), 966 – 969 & 2012 Cancer Research UK Exposure to animals and risk of lymphoma R Dolcetti et al Lee J, Kim Y, Kang CS, Cho DH, Shin DH, Yum YN, Oh JH, Kim SH, Doglioni C (2008) Chlamydia infection and lymphomas: association Hwang MS, Lim CJ, Yang KH, Han K (2005) Investigation of the bovine beyond ocular adnexal lymphomas highlighted by multiple detection leukemia virus proviral DNA in human leukemias and lung cancers in methods. Clin Cancer Res 14: 5794–5800 Korea. J Korean Med Sci 20: 603–606 Sprague LD, Schubert E, Hotzel H, Scharf S, Sachse K (2009) The detection Marcucci F, Mele A (2011) Hepatitis viruses and non-Hodgkin lymphoma: of Chlamydophila psittaci genotype C infection in dogs. Vet J 181: epidemiology, mechanisms of tumorigenesis, and therapeutic opportu- 274–279 nities. Blood 117: 1792–1798 Svec MA, Ward MH, Dosemeci M, Checkoway H, De Roos AJ (2005) McLean D, Pearce N (2004) Cancer among meat industry workers. Scand J Risk of lymphatic or haematopoietic cancer mortality with occupa- Work Environ Health 30: 425–437 tional exposure to animals or the public. Occup Environ Med 62: Moore T, Brennan P, Becker N, de SS, Maynadie M, Foretova L, Cocco P, 726–735 Staines A, Nieters A, Font R, Mannetje A, Benhaim-Luzon V, Boffetta P Tarsitano E, Greco G, Decaro N, Nicassio F, Lucente MS, Buonavoglia C, (2007) Occupational exposure to meat and risk of lymphoma: a Tempesta M (2010) Environmental monitoring and analysis of faecal multicenter case-control study from Europe. Int J Cancer 121: 2761–2766 contamination in an urban setting in the city of Bari (Apulia region, Moslehi R, Devesa SS, Schairer C, Fraumeni Jr JF (2006) Rapidly increasing Italy): health and hygiene implications. Int J Environ Res Public Health 7: incidence of ocular non-hodgkin lymphoma. J Natl Cancer Inst 98: 936–939 3972– 3986 Persson B, Fredrikson M (1999) Some risk factors for non-Hodgkin’s Tranah GJ, Bracci PM, Holly EA (2008) Domestic and farm-animal lymphoma. Int J Occup Med Environ Health 12: 135–142 exposures and risk of non-Hodgkin’s lymphoma in a population-based Ponzoni M, Ferreri AJ, Guidoboni M, Lettini AA, Cangi MG, Pasini E, study in the San Francisco Bay Area. Cancer Epidemiol Biomarkers Prev Sacchi L, Pecciarini L, Grassi S, Dal CE, Stefano R, Magnino S, Dolcetti R, 17: 2382–2387 & 2012 Cancer Research UK British Journal of Cancer (2012) 106(5), 966 – 969 Epidemiology

Journal

British Journal of CancerSpringer Journals

Published: Jan 24, 2012

There are no references for this article.