Statin use and risk of lymphoid neoplasms: Results from the European case-control study EPILYMPH

Background: Statins, drugs used to treat dyslipidemia, may have anticancer properties. We have evaluated lymphoma risk associated with regular statin use in an international case-control study. Methods: This case-control study included 2,362 cases of incident B- and T-cell lymphoma from Czech Republic, France, Germany, Ireland, Italy, and Spain and 2,206 hospital or population controls. Information on drug use, diagnosis at admission (for hospital controls), and putative risk factors for lymphoma was collected with personal interviews. Hospital controls admitted for diseases possibly entailing use of statins were excluded from the analysis. Results: The odds ratio for regular statin use was 0.61 (95% confidence interval, 0.45-0.84); all major lymphoma subtypes showed similarly decreased risks. Decreased risks were observed in all centers. Duration of statin use was not associated with a greater reduction in the risk of lymphoma. Use of other lipid lowering drugs, such as fibrates, did not significantly modify the risk of lymphoma (odds ratio, 0.75; 95% confidence interval, 0.44-1.27). Conclusion: Statin use was associated with an important reduction in lymphoma risk, adding to the growing evidence of anticancer properties of this group of drugs. These results are reassuring for the increasing number of patients taking statins on a regular basis. Copyright \ua9 2006 American Association for Cancer Research

Variation in DNA repair genes XRCC3, XRCC4, XRCC5 and susceptibility to myeloma

Cytogenetic analysis in myeloma reveals marked chromosomal instability. Both widespread genomic alterations and evidence of aberrant class switch recombination, the physiological process that regulates maturation of the antibody response, implicate the DNA repair pathway in disease pathogenesis. We therefore assessed 27 SNPs in three genes (XRCC3, XRCC4 and XRCC5) central to DNA repair in patients with myeloma and controls from the EpiLymph study and from an Irish hospital registry (n = 306 cases, 263 controls). For the haplotype-tagging SNP (htSNP) rs963248 in XRCC4, Allele A was significantly more frequent in cases than in controls (86.4 versus 80.8%; odds ratio 1.51; 95% confidence interval 1.10-2.08; P = 0.0133), as was the AA genotype (74 versus 65%) (P = 0.026). Haplotype analysis was performed using Unphased for rs963248 in combination with additional SNPs in XRCC4. The strongest evidence of association came from the A-T haplotype from rs963248-rs2891980 (P = 0.008). For XRCC5, the genotype GG from rs1051685 was detected in 10 cases from different national populations but in only one control (P = 0.015). This SNP is located in the 3'-UTR of XRCC5. Overall, these data provide support for the hypothesis that common variation in the genes encoding DNA repair proteins contributes to susceptibility to myeloma. \ua9 The Author 2007. Published by Oxford University Press. All rights reserved

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. \ua9 2010 by Lippincott Williams & Wilkins

Exposure to ultraviolet radiation and risk of malignant lymphoma and multiple myeloma - A multicentre European case - Control study

Background: Three recent studies have reported a decreased risk of non-Hodgkin lymphoma (NHL) for high ultraviolet (UV) radiation exposure. Methods: We conducted a multicentre case-control study during 1998-2004in France, Germany, Ireland, Italy and Spain, comprising 1518 cases of NHL, 268 cases of Hodgkin lymphoma, 242 cases of multiple myeloma and 2124 population or hospital controls. We collected information on sensitivity to sun and personal exposure to UV radiation in childhood and adulthood via interview, and assessed occupational exposure to UV radiation from the occupational history. Results: The risk of Hodgkin and NHL was increased for increasing skin sensitivity to the sun [odds ratio (OR) for no suntan vs very brown 2.35, 95% CI 0.94-5.87 and 1.39, 95% CI 1.03-1.87, respectively]. The risk of diffuse large B-cell lymphoma was reduced for increasing adult personal (OR for highest vs lowest quartile of exposure in free days 0.62, 95% CI 0.44-0.87) and for occupational exposure to UV radiation (OR for highest vs lowest exposure tertile 0.63, 95% CI 0.37-1.04). The risk of multiple myeloma was increased for personal exposure to UV radiation during adulthood (OR for highest vs lowest quartile of exposure in free days 1.49, 95% CI 0.88-2.50). A protective effect was observed for use of sun lamps for diffuse large B-cell lymphoma (OR for 25+ times vs never 0.63, 95% CI 0.38-1.03). Conclusions: The hypothesis of a protective effect of UV radiation on lymphoma is supported by our results. The underlying mechanisms might differ from those operating in skin carcinogenesis. The increased risk of multiple myeloma is worth replication. \ua9 The Author 2008; all rights reserved

Medical history and risk of lymphoma: Results of a European case-control study (EPILYMPH)

Introduction: Lymphomas are a heterogeneous group of immune-cell malignancies. Immunology-related conditions are among the few factors for which consistent evidence exists relating them to lymphoma risk. Materials and methods: We used the data from the European case-control study Epilymph on 2,362 lymphoma cases and 2,458 controls to investigate associations between a medical history of infectious and non-infectious diseases with overall and subentity-specific lymphoma risk. Results: As key results, we observed an increased odds ratio (OR) for self-reported infections with hepatitis B virus (HBV, OR = 1.91, 95% CL = 1.24-2.94) and a null result for rheumatoid arthritis. Additionally, we found an increased OR for infectious mononucleosis (OR = 1.68, 95% CL = 1.14-2.48), an inverse association to frequency of sickness in childhood (OR = 0.68, 95% CL = 0.55-0.84), and-as casual finding-an increased OR with acetaminophen intake (OR = 2.29, 95% CL = 1.49-3.51). Conclusion: Our results are consistent with the current knowledge about the association with mononucleosis as indicator of Epstein-Barr-virus infection, suggest serological study of the association to HBV infection and do not support the view of a positive association between rheumatoid arthritis and lymphoma risk. \ua9 2009 Springer-Verlag

Hepatitis B virus infection and risk of lymphoma: Results of a serological analysis within the European case-control study Epilymph

Background We have recently reported from Epilymph, a multicentre case-control study of lymphoma conducted in six European countries, a significant association between NHL and self-reported history of past or present HBV infection based on questionnaire data from face-to-face interviews. Methods To corroborate this observation, we used the data and blood specimen from Epilymph to investigate the associations between serological indicators of HBV infection with risk of Hodgkin lymphoma, non-Hodgkin lymphoma (NHL) and specific lymphoma entities. For 1,518 cases and 1,496 controls with sufficient amount of serum or plasma, we tested HBs-antigen, anti-HBc and anti-HBs to distinguish between current or past infection and immunity by vaccination. Statistical analysis was carried out with unconditional logistic regression. Results We found a positive association of a past HBV infection with multiple myeloma (MM, OR = 1.97, 95 % CL = 1.16-3.37). Non-significant associations were found between past HBV infection and B-cell chronic lymphocytic leukaemia (B-CLL, OR = 1.33, 95 % CL = 0.82-2.16) and T-cell NHL (OR = 1.59, 95 % CL = 0.65-3.90), as well as between current HBV infection and NHL (OR = 1.49, 95 % CL = 0.65-3.41), B-NHL (OR = 1.58, 95 % CL = 0.69-3.64) and diffuse large B-cell lymphoma (DLBCL, OR = 1.50, 95 % CL = 0.47-4.82). Subjects having self-reported HBV infection were serological positive in 75 % of cases and 80 % of controls. For vaccination, the corresponding figures were 49 and 54 %, respectively. Conclusion The present results support previous reports of an association between a history of HBV infection with an elevated lymphoma risk and add multiple myeloma to the list of potentially virus-associated lymphoma entities. \ua9 Springer-Verlag 2012

Lymphoma risk and occupational exposure to pesticides: Results of the Epilymph study

Objectives: We investigated the role of occupational exposure to specific groups of agrochemicals in the aetiology of lymphoma overall, B cell lymphoma and its most prevalent subtypes. Methods: In 1998-2003, 2348 incident lymphoma cases and 2462 controls were recruited to the EPILYMPH case-control study in six European countries. A detailed occupational history was collected in cases and controls. Job modules were applied for farm work including specific questions on type of crop, farm size, pests being treated, type and schedule of pesticide use. In each study centre, industrial hygienists and occupational experts assessed exposure to specific groups of pesticides and individual compounds with the aid of agronomists. We calculated the OR and its 95% CI associated with lymphoma and the most prevalent lymphoma subtypes with unconditional logistic regression, adjusting for age, gender, education and centre. Results: Risk of lymphoma overall, and B cell lymphoma was not elevated, and risk of chronic lymphocytic leukaemia (CLL) was elevated amongst those ever exposed to inorganic (OR=1.6, 95% CI 1.0 to 2.5) and organic pesticides (OR=1.5, 95% CI 1.0 to 2.1). CLL risk was highest amongst those ever exposed to organophosphates (OR=2.7, 95% CI 1.2 to 6.0). Restricting the analysis to subjects most likely exposed, no association was observed between pesticide use and risk of B cell lymphoma. Conclusions: Our results provide limited support to the hypothesis of an increase in risk of specific lymphoma subtypes associated with exposure to pesticides

Incidence, survival and prevalence of myeloid malignancies in Europe.

BACKGROUND: The Surveillance of Rare Cancers in Europe (RARECARE) project aims at increasing knowledge of rare cancers in Europe. This manuscript describes the epidemiology of myeloid malignancies (MMs), taking into account the morphological characterisation of these tumours. METHODS: We used data gathered by RARECARE on cancer patients diagnosed from 1995 to 2002 and archived in 64 European population-based cancer registries, followed up to 31st December 2003 or later. RESULTS: The overall annual crude incidence of MMs was 8.6 per 100,000. Acute myeloid leukaemia (AML) and myeloproliferative neoplasms (MPN) were most common, with incidence rates of 3.7 and 3.1 per 100,000 year respectively, followed by 1.8 for myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MD/MPN) and 0.1 for histiocytic and dendritic cell neoplasms (HDCN). The 5-year relative survival rate ranged from 18% for chronic myelomonocytic leukaemia, 19% for AML, 29% for MDS and 44% for chronic myeloid leukaemia to relatively favourable rates for MPN (62%) and HDCN (83%). Total number of new cases of MMs in the EU27 is estimated at 43,000 annually, total number of prevalent cases (1st January 2008) at 189,000 cases. CONCLUSION: MMs form a large variety of rare entities with specific characteristics. Collection of detailed information (immunophenotype, genetic abnormalities, molecular data and clinical data) and an up-to-date classification system is essential for their surveillance, especially now that more and more targeted therapies are being introduced

A pooled analysis of alcohol consumption and risk of multiple myeloma in the international multiple myeloma consortium

Background: Recent findings suggest that alcohol consumption may reduce risk of multiple myeloma. Methods: To better understand this relationship, we conducted an analysis of six case-control studies participating in the International Multiple Myeloma Consortium (1,567 cases, 7,296 controls). Summary ORs and 95% confidence intervals (CI) relating different measures of alcohol consumption and multiple myeloma risk were computed by unconditional logistic regression with adjustment for age, race, and study center. Results: Cases were significantly less likely than controls to report ever drinking alcohol (men: OR = 0.72; 95% CI, 0.59-0.89; women: OR = 0.81; 95% CI, 0.68-0.95). The inverse association with multiple myeloma was stronger when comparing current to never drinkers (men:OR=0.57; 95% CI, 0.45-0.72; women:OR=0.55; 95% CI, 0.45-0.68), but null among former drinkers. We did not observe an exposure-response relationship with increasing alcohol frequency, duration, or cumulative lifetime consumption. Additional adjustment for body mass index, education, or smoking did not affect our results; and the patterns of association were similar for each type of alcohol beverage examined. Conclusions: Our study is, to our knowledge, the largest of its kind to date, and our findings suggest that alcohol consumption may be associated with reduced risk of multiple myeloma. Impact: Prospective studies, especially those conducted as pooled analyses with large sample sizes, are needed to confirm our findings and further explore whether alcohol consumption provides true biologic protection against this rare, highly fatal malignancy. \ua9 2013 AACR

Atopic disease and risk of non-Hodgkin lymphoma: an InterLymph pooled analysis

We performed a pooled analysis of data on atopic disease and risk of non-Hodgkin lymphoma (NHL) from 13 case-control studies, including 13,535 NHL cases and 16,388 controls. Self-reported atopic diseases diagnosed 2 years or more before NHL diagnosis (cases) or interview (controls) were analyzed. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were computed in two-stage random-effects or joint fixed-effects models, and adjusted for age, sex, and study center. When modeled individually, lifetime history of asthma, hay fever, specific allergy (excluding hay fever, asthma, and eczema), and food allergy were associated with a significant reduction in NHL risk, and there was no association for eczema. When each atopic condition was included in the same model, reduced NHL risk was only associated with a history of allergy (OR, 0.80; 95% CI, 0.68-0.94) and reduced B-cell NHL risk was associated with history of hay fever (OR, 0.85; 95% CI, 0.77-0.95) and allergy (OR, 0.84; 95% CI, 0.76-0.93). Significant reductions in B-cell NHL risk were also observed in individuals who were likely to be truly or highly atopic - those with hay fever, allergy, or asthma and at least one other atopic condition over their lifetime. The inverse associations were consistent for the diffuse large B-cell and follicular subtypes. Eczema was positively associated with lymphomas of the skin; misdiagnosis of lymphoma as eczema is likely, but progression of eczema to cutaneous lymphoma cannot be excluded. This pooled study shows evidence of a modest but consistent reduction in the risk of B-cell NHL associated with atopy