European Multicentre Case-control Study Research Articles

Constitutional Factors and Irradiation as Risk Factors for Thymoma: A European Case-Control Study.

Little is known about the aetiology of thymoma. This study aims to identify medical risk factors for thymoma as a systematic approach to new hypotheses on the aetiology of this disease. A European multi-centre case-control study was conducted from 1995 to 1997, including incident cases aged 35-69 years with thymoma. Altogether, we accepted 85 cases and 3350 controls, of which we interviewed 77 cases and 2071 population controls about constitutional factors, medical examinations, and former diseases. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated. Medical examinations with X-ray or radiotherapy performed >20 times at least one year before the thymoma diagnosis indicated a possible risk factor for thymoma (OR 1.58, 95% CI 0.93-2.69). Having the first radiotherapy treatment at least one year before the thymoma diagnosis yielded an OR for thymoma of 2.39; 95% CI (0.96-5.99), and if it was at least five years before, the OR for thymoma was 2.81; 95% CI (1.03-7.72). Having a red/auburn hair colour was associated with thymoma, (OR 3.6, 95% CI 1.4-9.5) whereas having pigmented skin was slightly associated with thymoma (OR 1.8, 95% CI 0.8-3.8). Over twenty instances of X-ray examinations or radiotherapy were identified as potential risk factors for thymoma, along with certain constitutional factors. The observed correlations between benign tumours and thymoma could stem from an inherent predisposition to tumour development or result from detection bias. Given that this is the initial analytical study examining medical risk factors for thymoma, all of the results should be approached with caution, acknowledging the possibility that some findings might be incidental.

Tuberculosis Disease in Immunocompromised Children and Adolescents: A Pediatric Tuberculosis Network European Trials Group Multicenter Case-control Study.

In high-resource settings, the survival of children with immunocompromise (IC) has increased and immunosuppressive therapies are increasingly being used. This study aimed to determine the clinical characteristics, performance of diagnostic tools, and outcome of IC children with tuberculosis (TB) in Europe. Multicenter, matched case-control study within the Pediatric Tuberculosis Network European Trials Group, capturing TB cases <18 years diagnosed 2000-2020. A total of 417 TB cases were included, comprising 139 children who are IC (human immunodeficiency virus, inborn errors of immunity, drug-induced immunosuppression, and other immunocompromising conditions) and 278 non-IC children as controls. Nonrespiratory TB was more frequent among cases than controls (32.4% vs 21.2%; P = .013). Patients with IC had an increased likelihood of presenting with severe disease (57.6% vs 38.5%; P < .001; odds ratio [95% confidence interval], 2.073 [1.37-3.13]). Children with IC had higher rates of false-negative tuberculin skin test (31.9% vs 6.0%; P < .001) and QuantiFERON-TB Gold assay (30.0% vs 7.3%; P < .001) results at diagnosis. Overall, the microbiological confirmation rate was similar in IC and non-IC cases (58.3% vs 49.3%; P = .083). Although the mortality in children with IC was <1%, the rate of long-term sequelae was significantly higher than in non-IC cases (14.8% vs 6.1%; P = .004). Children with IC and TB in Europe have increased rates of nonrespiratory TB, severe disease, and long-term sequelae. Immune-based TB tests have poor sensitivity in those children. Future research should focus on developing improved immunological TB tests that perform better in patients with IC, and determining the reasons for the increased risk of long-term sequelae, with the aim to design preventive management strategies.

Genetic polymorphisms associated with telomere length and risk of developing myeloproliferative neoplasms

Telomere length measured in leukocyte (LTL) has been found to be associated with the risk of developing several cancer types, including myeloproliferative neoplasms (MPNs). LTL is genetically determined by, at least, 11 SNPs previously shown to influence LTL. Their combination in a score has been used as a genetic instrument to measure LTL and evaluate the causative association between LTL and the risk of several cancer types. We tested, for the first time, the “teloscore” in 480 MPN patients and 909 healthy controls in a European multi-center case–control study. We found an increased risk to develop MPNs with longer genetically determined telomeres (OR = 1.82, 95% CI 1.24–2.68, P = 2.21 × 10−3, comparing the highest with the lowest quintile of the teloscore distribution). Analyzing the SNPs individually we confirm the association between TERT-rs2736100-C allele and increased risk of developing MPNs and we report a novel association of the OBFC1-rs9420907-C variant with higher MPN risk (ORallelic = 1.43; 95% CI 1.15–1.77; P = 1.35 × 10−3). Consistently with the results obtained with the teloscore, both risk alleles are also associated with longer LTL. In conclusion, our results suggest that genetically determined longer telomeres could be a risk marker for MPN development.

Tobacco smoking and alcohol consumption as risk factors for thymoma – A European case-control study

PurposeHardly anything is known about the aetiology of thymoma. This paper presents data regarding tobacco smoking and alcohol consumption in relation to thymoma from the first case-control study performed on this rare tumour. MethodsA European multi-centre case-control study including incident cases aged 35–69 years with thymoma between 1995 and 1997, was conducted in seven countries. A set of controls, used in seven parallel case-control studies by the same research group was used, including population-based controls from five countries and hospital controls with colon cancer from two countries. Altogether 103 cases, accepted by a reference pathologist, 712 colon cancer controls, and 2071 population controls were interviewed. ResultsTobacco smoking was moderately related with thymoma (OR 1.4, 95% CI 0.9–2.2), and a tendency to dose-response was shown (p = 0.04), with an increased risk for heavy smokers defined as ≥41 pack-years (OR 2.1, 95% CI 1.1–3.9). A high consumption of spirits defined as ≥25 g of alcohol per day was associated with an increased risk of thymoma (OR 2.4, 95% CI 1.1–5.4), whereas no association was found with beer or wine. ConclusionsTobacco smoking and a high intake of spirits were indicated as risk factors for thymoma.

Exploring the effect of previous inactivated influenza vaccination on seasonal influenza vaccine effectiveness against medically attended influenza: Results of the European I-MOVE multicentre test-negative case-control study, 2011/2012-2016/2017.

BackgroundResults of previous influenza vaccination effects on current season influenza vaccine effectiveness (VE) are inconsistent.ObjectivesTo explore previous influenza vaccination effects on current season VE among population targeted for vaccination.MethodsWe used 2011/2012 to 2016/2017 I‐MOVE primary care multicentre test‐negative data. For each season, we compared current season adjusted VE (aVE) between individuals vaccinated and unvaccinated in previous season. Using unvaccinated in both seasons as a reference, we then compared aVE between vaccinated in both seasons, current only, and previous only.ResultsWe included 941, 2645 and 959 influenza‐like illness patients positive for influenza A(H1N1)pdm09, A(H3N2) and B, respectively, and 5532 controls. In 2011/2012, 2014/2015 and 2016/2017, A(H3N2) aVE point estimates among those vaccinated in previous season were −68%, −21% and −19%, respectively; among unvaccinated in previous season, these were 33%, 48% and 46%, respectively (aVE not computable for influenza A(H1N1)pdm09 and B). Compared to current season vaccination only, VE for both seasons' vaccination was (i) similar in two of four seasons for A(H3N2) (absolute difference [ad] 6% and 8%); (ii) lower in three of four seasons for influenza A(H1N1)pdm09 (ad 18%, 26% and 29%), in two seasons for influenza A(H3N2) (ad 27% and 39%) and in two of three seasons for influenza B (ad 26% and 37%); (iii) higher in one season for influenza A(H1N1)pdm09 (ad 20%) and influenza B (ad 24%).ConclusionsWe did not identify any pattern of previous influenza vaccination effect. Prospective cohort studies documenting influenza infections, vaccinations and vaccine types are needed to understand previous influenza vaccinations' effects.

Occupational exposure to organic solvents and risk of male breast cancer: a European multicenter case-control study.

Objectives The etiology of male breast cancer (MBC) is largely unknown but a causal role of exposure to organic solvents has been suggested. Previous studies on occupational risk factors of breast cancer were often restricted to women who are frequently exposed to lower levels and at a lower frequency than men. We investigated the association between MBC and occupational exposure to petroleum and oxygenated and chlorinated solvents in a multicenter case-control study of rare cancers in Europe. Methods The study included 104 MBC cases and 1901 controls. Detailed lifetime work history was obtained during interviews, together with sociodemographic characteristics, medical history and lifestyle factors. Occupational exposures to solvents were estimated from a job-exposure matrix. Odds ratios (OR) and their 95% confidence intervals (CI) were calculated using unconditional logistic regression models. Results Lifetime cumulative exposure to trichloroethylene >23.9 ppm years was associated with an increased MBC risk, compared to non-exposure [OR (95% CI): 2.1 (1.2-4.0); P trend <0.01). This increase in risk persisted when only exposures that occurred ≥10 years before diagnosis were considered. In addition, a possible role for benzene and ethylene glycol in MBC risk was suggested, but no exposure-response trend was observed. Conclusions These findings add to the evidence of an increased risk of breast cancer among men professionally exposed to trichloroethylene and possibly to benzene or ethylene glycol. Further studies should be conducted in populations with high level of exposure to confirm our results.

Skin cancer risk in outdoor workers: a European multicenter case-control study.

Exposure to ultraviolet radiation (UVR) is the most important external risk factor for skin cancer. Outdoor workers, who are exposed to high ambient UVR levels are at increased risk. To compare outdoor with indoor workers in terms of: (i) skin cancer risk factors, and (ii) risk of developing skin cancer. Using descriptive methods and a large multicenter European case-control study, we compared risk factor patterns between outdoor (N = 1416) and indoor workers (N = 1863). Risk of developing basal cell carcinoma (BCC), squamous cell carcinoma (SCC), melanoma and actinic keratosis (AK) were analysed by type of work using multivariate logistic regression models, for three categories of work: indoor; farming/construction; other outdoor work. Although skin phototype was equally distributed by type of work, significantly less outdoor than indoor workers used sunscreen in their own country (44.3% vs. 60.2%), but had more outdoor hobbies (66.2% vs. 58.2%). Outdoor workers had lower educational levels, and felt less confident in understanding medical information and filling medical forms (all P < 0.001). Outdoor workers had more signs of photodamage (78.1% vs. 65.5%) and among the skin cancer patients, 37.7% of outdoor workers vs. 28.6% of indoor workers had ≥2 skin cancers diagnosed during their lifetime. Multivariate logistic regression models showed significantly increased risk of outdoor vs. indoor work for AK (ORother outdoor = 1.55, ORfarming/construction = 2.58), SCC (ORother outdoor = 1.32, ORfarming/construction = 2.77) and BCC (ORother outdoor = 1.53, ORfarming/construction = 1.83). No significant associations were found for melanoma. The risk of all types of skin cancer and AK was significantly increased for workers with ≥5 years of outdoor work. Outdoor workers had more risk behaviour with similar constitutional skin cancer risk factors: more UV exposure (both occupational and leisure) and less sunscreen use and lower health literacy. This results in higher exposure, more photodamage and an increased risk of developing AK, BCC and SCC.

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Objectives In singleton pregnancies, sFlt-1, PlGF and the sFlt-1/PlGF-ratio have shown utility as a diagnostic test for preeclampsia (PE). Previous case control studies have determined cut-off values for singleton pregnancies. The objective of this study was to characterize angiogenic factor levels of sFlt-1, PlGF and sFlt-1/PlGF-ratio in normal and preeclamptic multifetal gestations. Methods In a European multicentre case-control study, 52 women with multifetal gestation were recruited. A total of 34 patients with uneventful pregnancy outcome and 18 with PE were enrolled in the third trimester. sFlt-1 and PlGF were measured and ROC analysis was performed. The results of the median sFlt-1, PlGF maternal serum concentration and sFlt-1/PlGF-ratio were then compared to a gestational age- matched singleton cohort with PE (n = 54) and with uncomplicated pregnancy outcome (n = 238). Results In multiple pregnancies with PE, sFlt-1 and the sFlt-1/PlGF ratio were increased and PlGF was decreased as compared to multiple gestations with uneventful pregnancy outcome. In multiple pregnancies with PE, sFlt-1/PlGF-Ratio was significantly decreased as compared to controls due to higher median PlGF levels. In multiple pregnancies with uneventful pregnancy outcome, sFlt-1 and sFlt-1/PlGF-ratio were increased, but no differences in PlGF concentration were found when compared to singleton controls. ROC analysis determined 53 as an optimal cut-off for the sFlt-1/PlGF-ratio, yielding a sensitivity of 94.4% and a specificity of 73.5%. The cut-off values for singleton pregnancies of 33 and 85 lead to a sensitivity of 100% (83.3%) and a specificity 64.7% (79.4%). Conclusions Significant differences in the marker levels in singleton-versus multiple gestations were detected. Established reference ranges for singleton pregnancies are therefore not transferable to multiple pregnancies. Disclosures L. Droge: None. I. Herraiz: Research Support Recipient; Commercial Interest: Roche Diagnostics. H. Zeisler: Consultant, Research Support Recipient, Commercial Interest: Roche Diagnostics; D. Schlembach: Research Support Recipient; Commercial Interest: Roche Diagnostics. H. Stepan: Consultant, Research Support Recipient, Commercial Interest: Roche Diagnostics.W. Henrich: None. A. Galindo: Research Support Recipient; Commercial Interest: Roche Diagnostics. S. Verlohren: Consultant, Research Support Recipient, Commercial Interest: Roche Diagnostics, ThermoFisher, Novartis.

Physical activity and risk of pancreatic cancer in a central European multicenter case-control study.

Findings from epidemiological studies examining physical activity in relation to pancreatic cancer risk have suggested decreased risks for physical activity; however, the results are inconsistent. The association between occupational and leisure-time physical activity and risk of pancreatic cancer was examined among 826 pancreatic cancer cases and 930 age-, sex- and center-matched controls from a large multicenter central European study in Czech Republic and Slovakia recruited between 2004 and 2012. Data on physical activity including type and dose (frequency, intensity, and duration) were examined using multivariable-adjusted logistic regression models. Occupational physical activity was not significantly associated with risk of pancreatic cancer [odds ratio (OR) 0.90, 95 % confidence interval (CI) 0.71-1.15]. A 35 % decrease in risk of pancreatic cancer was observed for regular leisure-time physical activity (OR 0.65, 95 % CI 0.52-0.87). The risk estimates were significant for low and moderate intensity of activity with the strongest protective effect among individuals who exercised during more than 40 weeks per year. The results for cumulated leisure-time physical activity assessed 1 year prior to diagnosis achieved the same level of risk reduction. In addition, stronger risk estimates for leisure-time physical activity were observed among women (men: OR 0.74, 95 % CI 0.54-1.01; women: OR 0.53, 95 % CI 0.37-0.75). The findings for female participants were stronger for intensity and frequency of leisure-time physical activity, in particular for light and moderate activity (OR 0.43, 95 % CI 0.25-0.75; and OR 0.57, 95 % CI 0.37-0.88, respectively). These results provide evidence for a decreased risk of pancreatic cancer associated with regular leisure-time physical activity.

Risk of upper aerodigestive tract cancer and type of alcoholic beverage: a European multicenter case–control study

The general relationship between cancers of the upper aerodigestive tract (UADT) and alcohol drinking is established. Nevertheless, it is uncertain whether different types of alcoholic beverages (wine, beer and liquor) carry different UADT cancer risks. Our study included 2,001 UADT cancer cases and 2,125 controls from 14 centres in 10 European countries. All cases were histologically or cytologically confirmed squamous cell carcinomas. Controls were frequency matched by sex, age and centre. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95%CI) adjusted for age, sex, centre, education level, vegetable and fruit intake, tobacco smoking and alcohol drinking, where appropriate. Risk of beverage-specific alcohol consumption were calculated among 'pure drinker' who consumed one beverage type exclusively, among 'predominant drinkers' who consumed one beverage type to more than 66% and among 'mixed drinkers' who consumed more than one beverage type to similar proportions. Compared to never drinkers and adjusted for cumulative alcohol consumption, the OR and 95%CI for wine, beer and liquor drinking, respectively, were 1.24 (0.86, 1.78), 1.54 (1.05, 2.27) and 0.94 (0.53, 1.64) among 'pure drinkers' (p value for heterogeneity across beverage types=0.306), 1.05 (0.76,1.47), 1.25 (0.87,1.79) and 1.43 (0.95, 2.16) among 'predominant drinkers' (p value=0.456), and 1.09 (0.79, 1.50), 1.20 (0.88, 1.63) and 1.12 (0.82, 1.53) among 'mixed drinkers' (p value=0.889). Risk of UADT cancer increased with increasing consumption of all three alcohol beverage types. Our findings underscore the strong and comparable carcinogenic effect of ethanol in wine, beer and liquor on organs of the UADT.

Antenatal screening forToxoplasma gondiiinfection at a tertiary care hospital in Riyadh, Saudi Arabia

BACKGROUND AND OBJECTIVES:Congenital toxoplasmosis is associated with significant morbidity and mortality. This study investigates the prevalence of toxoplasmosis among pregnant women.DESIGN AND SETTING:A retrospective study at King Khalid University Hospital, Riyadh from September 2009 to August 2010.PATIENTS AND METHODS:Laboratory data of 2176 pregnant women screened for Toxoplasma gondii in the antenatal care unit were assessed during the study period. The mean (SD) age of the women and the duration of pregnancy were 25 (7.3) years and 18 (7.7) weeks, respectively. Data were extracted for the presence or absence of anti-T gondii immunoglobulin G (IgG) and IgM antibodies.RESULTS:Of 2176 sera tested, 1351 (62%) did not show any evidence of exposure to T gondii. The remaining 825 (38%) samples tested positive for anti-T gondii IgG antibodies, and none was found to have anti-T gondii IgM antibodies in the serum. These data reveal that a significantly high number of women in the antenatal care unit at King Khalid University Hospital in Riyadh had been exposed to T gondii.CONCLUSION:A high prevalence of toxoplasmosis among pregnant women warrants multicenter community-based investigations for assessment of T gondii infection and identification of risk factors for transmission of toxoplasmosis in general, and particularly during pregnancy.

Body mass index and body size in early adulthood and risk of pancreatic cancer in a central European multicenter case–control study

The relationship between two measures of excess body weight, body mass index (BMI) and body size score, and risk of pancreatic cancer was examined among 574 pancreatic cancer cases and 596 frequency-matched controls from the Czech Republic and Slovakia enrolled between 2004 and 2009. Analyses using multivariable logistic regression showed an increased risk of pancreatic cancer associated with elevated quartiles of BMI at ages 20 [fourth quartile: odds ratio (OR) = 1.79, 95% confidence interval (CI): 1.23, 2.61] and 40 (fourth quartile: OR = 1.57, 95% CI: 1.09, 2.27) compared to the lowest quartile. Consistent results were observed for body size score at ages 20 (high versus low: OR = 1.66, 95% CI: 1.08, 2.57) and 40 (medium versus low: OR = 1.36, 95% CI: 1.00, 1.86), but no association was found for BMI and body size score at 2 years before the interview. Stronger risk estimates for BMI were observed in males than females, particularly at age 20, but the analysis of body size yielded similar estimates by sex. When considering excess body weight at both ages 20 and 40 jointly, the highest risk estimates were observed among subjects with elevated levels at both time periods in the analysis of BMI (OR = 1.86, 95% CI: 1.32, 2.62) and body size (OR = 1.53, 95% CI: 1.09, 2.13). These findings, based on two different measures, provide strong support for an increased risk of pancreatic cancer associated with excess body weight, possibly strongest during early adulthood.

Gene-nutrition interactions that modify the risk of upper aero-digestive tract cancer. Screening results of a European multi-center case-control study

Gene-nutrition interactions that modify the risk of upper aero-digestive tract cancer. Screening results of a European multi-center case-control study

Occupational exposure to pesticides and bile tract carcinoma in men: results from a European multicenter case–control study

To estimate the associations between occupational exposure to pesticides and extrahepatic biliary tract carcinoma in men, a population-based case-control study was carried out. Cases (n = 104), aged 35-70, diagnosed in 1995-1997, were sampled by active reporting systems from hospitals. Controls (n = 1,401) were a random sample of the general male population. Information on occupation and confounding factors was obtained by questionnaires. Exposures were quantified with respect to time, application methods, and use of personal protective equipment. Intensity was evaluated by using a published algorithm which weighted the exposure assigned according to the use of personal protective equipment and mode of application. Logistic regression analyses were conducted adjusted for gallstones, age, and country. Being ever exposed to pesticides resulted in an odds ratio (OR) of 1.0 [95%-confidence interval (CI) 0.6-1.6]. A modestly elevated risk was found for backpack mounted sprayers OR = 1.4 [95% CI 0.7-2.6] and vine farmers OR = 2.5 [95% CI 0.9-7.2]. Using time periods and exposure frequency as intensity measure, no elevated risks were found. The only exception was year of maximum exposure which yielded an OR of 1.6 [95% CI 0.7-3.5]. However, no clear trend was observed in this analysis. This study does not rule out that pesticide exposure represents an occupational risk factor for extrahepatic biliary tract carcinoma, but no indication of a strong association was observed. Some modes of exposure were weakly, albeit not significantly associated with carcinoma risk. The observed estimates of effects may be influenced by a lack of precise exposure assessment. Different chemical compositions of pesticides were utilized during a long time span of pesticide exposure, and it should be considered that the exposure is assessed with substantial uncertainty that could non-differential and bias results toward the null.

Alcohol drinking and the risk of upper aero digestive tract cancer: European multicenter case-control study ARCAGE

The aim of the research was to determine the satisfaction of patients diagnosed with colorectal cancer, with the actual bowel preparation prior to surgery, and the effectiveness of bowel emptying according to the protocol of a single procedure proposed by the authors. We studied two approaches of nurses to patients during mechanical bowel preparation. The first approach was connected with bowel emptying prior to planned surgery (according to the standard procedure of surgical wards), and the second one according to the protocol proposed by the authors. Data on patient satisfaction with the preoperative preparation were acquired using a questionnaire of our own design. The questionnaire was comprised of 26 questions compiled using the Likert scale. The reliability of the questionnaire was examined using the Cronbach alpha coefficient, and the resulting value was 0.906. Several statistical methods were used in the research: Chi-square test, F-test, Student's t-test, Mann–Whitney test, significance α = 0.05 and Cramer V coefficient. The examined issue was verified in the Slovak Republic and the Czech Republic in surgery clinics at the F.D. Roosevelt Teaching Hospital with Policlinic Banska Bystrica, the Teaching Hospital Brno, University Hospital Martin, and T. Bata Regional Hospital Zlin.It was found that our suggested protocol for bowel preparation, which focuses on patient satisfaction in the preparation process for surgery and efficient bowel emptying, is assessed more positively by patients and surgeons than the traditional standard procedure for bowel emptying. We recommended the proposed protocol be put into practice as a standard part of nursing documentation for patients being prepared for colon surgery at the Surgery Clinic II of the Slovak Medical University, F.D. Roosevelt Teaching Hospital with Policlinic Banska Bystrica.

Exposure to Occupational Contaminants and Risk of Male Breast Cancer: A European Case-Control Study

P-171 Abstract: Several environmental exposures have been suspected to play a role in breast cancer etiology, including organochlorine pesticides or other endocrine disrupting chemicals, polycyclic aromatic hydrocarbons (PAHs), and organic solvents, but epidemiological studies of breast cancer have produced inconsistent results. Exposure to these contaminants may also take place in occupational settings. Although male breast cancer is a rare disease, the study of breast cancers in males offers several advantages over a study of breast cancer in females because occupational exposures are usually much higher, and hence more easily assessed in men than in women, and because confounding or effect modification from reproductive risk factors cannot occur. We investigated occupational risk factors for male breast cancer in a European multicenter population-based case-control study that permitted to identify a relatively large numbers of cases. The study included 104 cases of male breast cancer aged 35 to 70 years and 2106 controls in eight European countries. Controls were selected from population registers in all countries, with the exception of Spain and Portugal where colon cancer controls only were available. All study subjects were interviewed across Europe using the same structured questionnaire that included a detailed work history. Occupational exposures to pesticides, PCBs, PAHs, alkylphenols, bisphenol-A, and phthalates were identified through a job-exposure matrix and then individually assessed by an expert using the detailed job description. A job-exposure matrix for petroleum solvents (e.g., benzene, white spirit) is also used. Analyses are carried out to identify the job groups at increased risk for male breast cancer and to examine breast cancer risk according to exposure indicators for specific chemicals. A statistically significant increased risk was observed in printers (OR=2.8 95%CI), painters (OR=2.5 95%CI 1.1–5.7), foundry workers (OR=4.6 95% CI 1.3–17.0), and motor vehicle mechanics (OR=2.0 95% CI 1.1–4.8). Workers in these occupational groups may have been exposed to suspected carcinogens for breast cancer, including organic solvents, gasoline, PAHs and combustion products. Confounding from other risk factors for male breast cancer such as alcohol drinking could not explain these results. The analyses for the specific occupational exposures will permit to further scrutinize these findings. Our results confirm that environmental factors may play a role in breast cancer, and suggest that additional studies on environmental factors in female breast cancer should be conducted.

Hepatitis C and Risk of Lymphoma: Results of the European Multicenter Case-Control Study EPILYMPH

Increasing evidence points toward a role of hepatitis C virus (HCV) infection in the etiology of malignant lymphomas. However, previous epidemiologic studies were limited in size to establish an association between HCV infection and specific lymphoma subtypes. We performed a large, multicenter, case-control study to address this question. The study comprised 5 European countries and included newly diagnosed cases of any lymphoid malignancy recruited between 1998 and 2004. Controls were matched to cases by 5-year age group, sex, and study center. In-person interviews were conducted to collect data on demographic, medical, and family history as well as environmental exposures. Serum samples of 1807 cases and 1788 controls (excluding human immunodeficiency virus-positive and organ-transplantation subjects) were screened for HCV infection using an enzyme immunoassay. Positive as well as randomly selected negative samples were subjected to HCV RNA detection and HCV genotyping. HCV infection was detected in 53 (2.9%) lymphoma cases and in 41 (2.3%) control subjects (odds ratio [OR], 1.42; 95% confidence interval [CI]: 0.93-2.15). Restricted to individuals who tested positive for HCV-RNA (indicating persistent infection and active viral replication), the OR was 1.82 (95% CI: 1.13-2.91). In subtype-specific analyses, HCV prevalence was associated with diffuse large B-cell lymphoma (OR, 2.19; 95% CI: 1.23-3.91) but not with chronic lymphocytic leukemia or follicular, Hodgkin's, or T-cell lymphoma. The sample size was not sufficient to derive any conclusions for rare lymphoma entities such as splenic marginal zone lymphoma. These results support a model that chronic HCV replication contributes to lymphomagenesis and establish a specific role of HCV infection in the pathogenesis of diffuse large B-cell lymphoma.

Lack of genetic association between the phospholipase A2 gene and bipolar mood disorder in a European multicentre case–control study

The possible association between phospholipase A2 gene and bipolar mood disorder was examined in 557 bipolar patients and 725 controls (all personally interviewed), recruited from seven countries (Belgium, Bulgaria, Croatia, Germany, Greece, Italy, and UK). The frequencies of the eight alleles that were identified did not differ between patients and control individuals in the whole population, while the power to detect an association based on our sample was relatively high. Some differences were noted among the various ethnic groups, but no significant trends existed, suggesting that population stratification by country may not be responsible for a type II error. On the basis of these results, mutations of the phospholipase A2 gene, at least in the region close to the polymorphism examined between exons 1 and 2, are not involved in the pathogenesis of bipolar mood disorder.

Occupational Sun Exposure and Mycosis Fungoides: A European Multicenter Case???Control Study

We sought to study the association between occupational sun exposure and mycosis fungoides (MF), a peripheral T-cell lymphoma. A European multicenter case-control study including seven rare cases (one being MF) was conducted between 1995 and 1997. From the 118 accepted cases, 104 were interviewed, of which 76 were definite cases. Population controls were selected randomly from the regions of case ascertainment. Information based on occupational experiences was coded according to industry types. A job exposure matrix was created according to the expected exposure to sunlight. Once exposures to aromatic halogenated hydrocarbons were eliminated (odds ratio = 2.3; 95% confidence interval = 0.9-6.2), a high MF risk was associated with exposures to solar radiation. It would appear that workers exposed to sunlight have a higher risk of MF. However, this factor is not the only one involved.

Occupational Exposures and Mycosis Fungoides. A European Multicentre Case–control Study (Europe)

Mycosis Fungoides (MF) is a rare disease with an occurrence indicating that occupational exposures may play a role. To estimate the association between MF and occupational exposures as measured by means of an job-exposure matrix (JEM). A European multicenter case-control study was conducted from 1995 to 1997 and included seven rare cancers, one of which was MF. Patients between 35 and 69 years of age, diagnosed with MF (n=140), were recruited and the diagnoses were checked by a reference pathologist who classified 83 cases as definite, 35 cases as possible and 22 cases as not accepted. Among the 118 accepted cases, 104 cases were interviewed, of which 76 were definite cases. We selected population controls and colon cancer controls to serve all seven case groups. Altogether 833 colon cancer controls and 2071 population controls were interviewed. Based on the reported occupational experiences, a team of industrial hygiene specialists identified five potential exposures and developed an JEM. This JEM was used to estimate the odds ratios (OR) for MF as a function of these exposures. The JEM included aromatic and/or halogenated hydrocarbons (AAHs), chrome (VI) and its salts, electromagnetic radiations, silica and pesticides. Exposures to AHHs (OR 6.3, C.I 2.4-16.7 for male) were associated with a high MF risk. The study supports the hypothesis that some MFs have an occupational etiology but only a small fraction of exposed workers are apparently susceptible since the disease is so rare.