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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Lifestyle-related factors and environmental agents causing cancer: an overview.

The increasing incidence of a variety of cancers after the Second World War confronts scientists with the question of their origin. In Western countries, expansion and ageing of the population as well as progress in cancer detection using new diagnostic and screening tests cannot fully account for the observed growing incidence of cancer. Our hypothesis is that environmental factors play a more important role in cancer genesis than it is usually agreed. (1) Over the last 2-3 decades, alcohol consumption and tobacco smoking in men have significantly decreased in Western Europe and North America. (2) Obesity is increasing in many countries, but the growing incidence of cancer also concerns cancers not related to obesity nor to other known lifestyle-related factors. (3) There is evidence that the environment has changed over the time period preceding the recent rise in cancer incidence, and that this change, still continuing, included the accumulation of many new carcinogenic factors in the environment. (4) Genetic susceptibility to cancer due to genetic polymorphism cannot have changed over one generation and actually favours the role of exogenous factors through gene-environment interactions. (5) Age is not the unique factor to be considered since the rising incidence of cancers is seen across all age categories, including children, and adolescents. (6) The fetus is specifically vulnerable to exogenous factors. A fetal exposure during a critical time window may explain why current epidemiological studies may still be negative in adults. We therefore propose that the involuntary exposure to many carcinogens in the environment, including microorganisms (viruses, bacteria and parasites), radiations (radioactivity, UV and pulsed electromagnetic fields) and many xenochemicals, may account for the recent growing incidence of cancer and therefore that the risk attributable to environmental carcinogen may be far higher than it is usually agreed. Of major concern are: outdoor air pollution by carbon particles associated with polycyclic aromatic hydrocarbons; indoor air pollution by environmental tobacco smoke, formaldehyde and volatile organic compounds such as benzene and 1,3 butadiene, which may particularly affect children and food contamination by food additives and by carcinogenic contaminants such as nitrates, pesticides, dioxins and other organochlorines. In addition, carcinogenic metals and metalloids, pharmaceutical medicines and some ingredients and contaminants in cosmetics may be involved. Although the risk fraction attributable to environmental factors is still unknown, this long list of carcinogenic and especially mutagenic factors supports our working hypothesis according to which numerous cancers may in fact be caused by the recent modification of our environment.

The multitude and diversity of environmental carcinogens.

We have recently proposed that lifestyle-related factors, screening and aging cannot fully account for the present overall growing incidence of cancer. In order to propose the concept that in addition to lifestyle related factors, exogenous environmental factors may play a more important role in carcinogenesis than it is expected, and may therefore account for the growing incidence of cancer, we overview herein environmental factors, rated as certainly or potentially carcinogenic by the International Agency for Research on Cancer (IARC). We thus analyze the carcinogenic effect of microorganisms (including viruses), radiations (including radioactivity, UV and pulsed electromagnetic fields) and xenochemicals. Chemicals related to environmental pollution appear to be of critical importance, since they can induce occupational cancers as well as other cancers. Of major concerns are: outdoor air pollution by carbon particles associated with polycyclic aromatic hydrocarbons; indoor air pollution by environmental tobacco smoke, formaldehyde and volatile organic compounds such as benzene and 1,3 butadiene, which may particularly affect children, and food pollution by food additives and by carcinogenic contaminants such as nitrates, pesticides, dioxins and other organochlorines. In addition, carcinogenic metals and metalloids, pharmaceutical medicines and cosmetics may be involved. Although the risk fraction attributable to environmental factors is still unknown, this long list of carcinogenic and especially mutagenic factors supports our working hypothesis according to which numerous cancers may in fact be caused by the recent modification of our environment.

The growing incidence of cancer: role of lifestyle and screening detection (Review).

The increasing incidence of a variety of cancers after the Second World War confronts scientists with the question of their origin. In Western countries, expansion and ageing of the population, as well as progress in cancer detection using new diagnostic and screening tests cannot fully account for the observed growing incidence of cancer. Our hypothesis is that environmental factors play a more important role in cancer genesis than it is usually agreed: i) over the last 2-3 decades, alcohol consumption and tobacco smoking in men have significantly decreased; ii) obesity is increasing in many countries, but the growing incidence of cancer also concerns cancers not related to obesity nor to other lifestyle-related factors; iii) there is evidence that the environment has changed over the same time scale as the recent rise in cancer incidence, and that this change included the accumulation of many new carcinogenic factors in the environment; iv) genetic susceptibility to cancer due to genetic polymorphism cannot have changed over one generation and actually favours the role of exogenous factors through gene-environment interactions; v) age is not the unique factor to be considered since the rising incidence of cancers is seen across all age categories, including children; vi) the fetus is specifically vulnerable to exogenous factors. A fetal exposure during a critical window period may explain why current epidemiological studies may be negative in adults. We therefore propose that the involuntary exposure to many carcinogens in the environment contributes to the rising trend in cancer incidence.

Use of cellular and cordless telephones and risk of testicular cancer.

A case-control study on testicular cancer included use of cellular and cordless telephones. The results were based on answers from 542 (92%) cases with seminoma, 346 (89%) with non-seminoma, and 870 (89%) controls. Regarding seminoma the use of analog cellular phones gave odds ratio (OR) = 1.2, 95% confidence interval (CI) = 0.9-1.6, digital phones OR = 1.3, CI = 0.9-1.8, and cordless phones OR = 1.1, CI = 0.8-1.5. The corresponding results for non-seminoma were OR = 0.7, CI = 0.5-1.1, OR = 0.9, CI = 0.6-1.4, and OR = 1.0, CI = 0.7-1.4, respectively. There was no dose-response effect and OR did not increase with latency time. No association was found with place of keeping the mobile phone during standby, such as trousers pocket. Cryptorchidism was associated both with seminoma (OR = 4.2, CI = 2.7-6.5) and non-seminoma (OR = 3.3, CI = 2.0-5.6), but no interaction was found with the use of cellular or cordless telephones.

Levels of brominated flame retardants in blood in relation to levels in household air and dust.

Levels of tri- to decabrominated diphenyl ethers (BDEs), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) and 1,2-bis(pentabromophenyl)ethane (DeBDethane) were determined in air, sedimentary dust and human plasma from five households in Sweden. The levels of the individual BDEs in the plasma samples were in the same order of magnitude as in other studies of the general population in Scandinavia, and varied between non-detectable (<0.41 ng g(-1) l.w.) to 17 ng g(-1) (l.w.). BDE#28 and #47 were present in all air samples, with mean values of 0.015 and 0.12 ng m(-3), respectively, except for one sample where the BDE#47 concentration was below the limit of detection (<0.17 ng m(-3)). BDE#209 was found in one of the five air samples at a concentration of 0.26 ng m(-3). DeBDethane was also detected in one sample, in which the BDE#209 level was below LOD (<0.021 ng m(-3)), at a level of 0.023 ng m(-3). All the target compounds were found in the sedimentary dust samples at levels from 0.51 to 1600 ng g(-1), the highest concentration representing BDE#209. The most abundant components in plasma, air and dust were BDE#47, #99 and #209. In the plasma samples BDE#207 and #206 were also present at similar concentrations as BDE#47. In the sedimentary dust samples, DeBDethane was also among the most abundant BFRs. A positive relationship was found for the sumBDE concentrations in dust and plasma, although the relationship was strongly dependent on one of the five observations. BFR levels in dust and air were not dependent on the house characteristics such as living area, floor material or number of electronic devices.

Use of cellular telephones and brain tumour risk in urban and rural areas.

AIMS: To investigate the association between the use of cellular or cordless telephones and the risk for brain tumours in different geographical areas, urban and rural. METHODS: Patients aged 20-80 years, living in the middle part of Sweden, and diagnosed between 1 January 1997 and 30 June 2000 were included. One control matched for sex and age in five year age groups was selected for each case. Use of different phone types was assessed by a questionnaire. RESULTS: The number of participating cases was 1429; there were 1470 controls. An effect of rural living was most pronounced for digital cellular telephones. Living in rural areas yielded an odds ratio (OR) of 1.4 (95% CI 0.98 to 2.0), increasing to 3.2 (95% CI 1.2 to 8.4) with >5 year latency time for digital phones. The corresponding ORs for living in urban areas were 0.9 (95% CI 0.8 to 1.2) and 0.9 (95% CI 0.6 to 1.4), respectively. This effect was most obvious for malignant brain tumours. CONCLUSION: In future studies, place of residence should be considered in assessment of exposure to microwaves from cellular telephones, although the results in this study must be interpreted with caution due to low numbers in some of the calculations.

How to combine the use of different mobile and cordless telephones in epidemiological studies on brain tumours?

Mobile phone users in epidemiological studies have often used more than one phone model, and sometimes also more than one mobile phone system (analogue and digital systems). Until now, this has not been taken into account in epidemiological studies, mainly because we do not know the possible interaction mechanism(s) and, hence, how to integrate exposure from different phones into one dosimetric measure. In this paper we take a step towards starting a discussion about how to proceed with this important issue and the possible use of parameters such as weighting factors, measured specific absorption rate (SAR) values and integrated specific absorption values are discussed. As a base of this discussion two previously published studies are used, one on mobile phones and cancer and the other one on subjective symptoms.

No association between the use of cellular or cordless telephones and salivary gland tumours.

AIM: To investigate the association between the use of cellular or cordless telephones and the risk for salivary gland tumours. METHODS: Cases were assessed from the six regional cancer registries in Sweden. Four controls matched for sex and age in five year age groups were selected for each case. A total of 293 living cases and 1172 controls were included. RESULTS: There were 267 (91%) participating cases and 1053 (90%) controls. Overall no significantly increased risk was found. Odds ratios were 0.92 (95% CI 0.58 to 1.44) for use of analogue phones, 1.01 (95% CI 0.68 to 1.50) for use of digital phones, and 0.99 (95% CI 0.68 to 1.43) for use of cordless phones. Similar results were found for different salivary gland localisations. No effect of tumour induction period or latency was seen, although few subjects reported use for more than 10 years. CONCLUSIONS: No association between the use of cellular or cordless phones and salivary gland tumours was found, although this study does not permit conclusions for long term heavy use.

Viral infection, atopy and mycosis fungoides: a European multicentre case-control study.

Mycosis fungoides (MF) is a rare disease with an unknown aetiology, although it has been suggested that infections may play a role. The present study investigates whether infections, atopic disorders and some other diseases are risk indicators for MF. A European multicentre case-control study involving seven rare cancers, including MF, was conducted from 1995 to 1998. Patients between 35 and 69 years of age diagnosed with MF (n = 140) were recruited, and the diagnoses were verified by a reference pathologist, who classified 83 cases as definitive and 35 cases as possible; 22 cases were not accepted. Of the 118 accepted cases, 104 patients were interviewed (including 76 definitive cases and 28 possible cases). These 76 definitive cases were used for this study. A common set of controls to serve all case groups were interviewed, representing a total of 4574 controls. The latter included 1008 colon cancer patients and 3566 subjects selected from population registers. Information on infections, skin pathology and clinical history 5 years before the diagnosis of MF was used to estimate odds ratios (ORs) derived from logistic regression-modelling, which included gender, age and country. The highest ORs for MF were found in patients who reported a history of psoriasis 5 years before MF was diagnosed (OR 7.2, 95% CI: 3.6-14.5). Urticaria had an OR of 1.4 (95% CI: 0.6-3.6). Infections and atopic diseases were not closely associated with MF. Some diseases correlated to MF. Whether this has a causal background or reflects early diagnostic uncertainty is not known.

Expression of p53, PCNA, Ki-67 and bcl-2 in relation to risk factors in oral cancer - a molecular epidemiological study.

A group of 133 primary oral squamous cell carcinomas were studied concerning a relationship between exposure factors and tumour biological parameters with a focus on the TP53 gene and p53 protein status. Tumours were evaluated using immunohistochemistry (IHC) for expression of p53, PCNA, Ki-67 and bcl-2 proteins. The TP53 gene was studied for mutations using PCR amplification of exons 5-9 and single strand conformation polymorphism (SSCP) analysis. The collected data were correlated to the exposure factors smoking, oral snuff, liquor, oral infections, dental factors, dental X-ray and iron deficiency. When compared with matched controls only oral infections, and reported HSV-infections in particular, gave statistically significant ORs (odds ratio) for all tumours (OR 8.0) as well as for the group of IHC p53 positive tumours (OR 12). No association between smoking and p53 positivity was found (OR 1.0).

Case-control study on the use of cellular and cordless phones and the risk for malignant brain tumours.

PURPOSE: To investigate the use of cellular and cordless phones and the risk for malignant brain tumours. MATERIALS AND METHODS: A case-control study was performed on 649 patients aged 20-80 years of both sexes with malignant brain tumour diagnosed from 1 January 1997 to 30 June 2000. All patients were alive during the time of the study and had histopathology verified brain tumours. One matched control to each case was selected from the Swedish Population Register. The study area was the Uppsala-Orebro, Stockholm, Linköping and Göteborg medical regions of Sweden. RESULTS: Exposure was assessed by a questionnaire answered by 588 (91%) cases and 581 (90%) controls. Phone usage was defined as 'ever use' and usage starting within 1 year before diagnosis was disregarded. Overall, no significantly increased risks were found: analogue cellular phones yielded an odds ratio (OR)=1.13, 95% confidence interval (CI)=0.82-1.57, digital cellular phones OR=1.13, CI=0.86-1.48, and cordless phones OR=1.13, CI=0.85-1.50. For ipsilateral (same side) radiofrequency exposure, analogue mobile phones gave OR=1.85, CI=1.16-2.96, for all malignant brain tumours. For astrocytoma, this risk was OR=1.95, CI=1.12-3.39. For all malignant brain tumours, digital mobile phones yielded OR=1.59, CI=1.05-2.41, and cordless phones yielded OR=1.46, CI=0.96-2.23, in the analysis of ipsilateral exposure. CONCLUSION: The ipsilateral use of an analogue cellular phone yielded a significantly increased risk for malignant brain tumours.

Cellular and cordless telephones and the risk for brain tumours.

Microwave exposure from the use of cellular telephones has been discussed in recent years as a potential risk factor for brain tumours. We included in a case-control study 1617 patients aged 20-80 years of both sexes with brain tumour diagnosed between 1 January 1997 and 30 June 2000. They were alive at the study time and had histopathologically verified brain tumour. One matched control to each case was selected from the Swedish Population Register. The study area was the Uppsala-Orebro, Stockholm, Linköping and Göteborg medical regions of Sweden. Exposure was assessed by a questionnaire that was answered by 1429 (88%) cases and 1470 (91%) controls. In total, use of analogue cellular telephones gave an increased risk with an odds ratio (OR) of 1.3 (95% confidence interval (CI) 1.02-1.6). With a tumour induction period of >10 years the risk increased further: OR 1.8 (95% CI 1.1-2.9). No clear association was found for digital or cordless telephones. With regard to the anatomical area of the tumour and exposure to microwaves, the risk was increased for tumours located in the temporal area on the same side of the brain that was used during phone calls; for analogue cellular telephones the OR was 2.5 (95% CI 1.3-4.9). Use of a telephone on the opposite side of the brain was not associated with an increased risk for brain tumours. With regard to different tumour types, the highest risk was for acoustic neurinoma (OR 3.5, 95% CI 1.8-6.8) among analogue cellular telephone users.

Adipose tissue concentrations of dioxins and dibenzofurans, titers of antibodies to Epstein-Barr virus early antigen and the risk for non-Hodgkin lymphoma.

A rapid increase in the incidence of non-Hodgkin lymphoma (NHL) has been reported in many countries. Exposure to certain pesticides or organochlorines has been shown to be a risk factor. Epstein-Barr virus (EBV) is a human herpesvirus that has been associated with some subgroups of NHL, such as Burkitt lymphoma and lymphomas related to severe immunosuppression. In this study we measured concentrations of dioxins and dibenzofurans in 33 NHL cases and 39 surgical controls. For 23 of the cases and 32 of the controls EBV titers were also available. Median titer of antibodies to EBV early antigen (EA) IgG was higher in patients than in controls. Concentrations of dioxins and dibenzofurans were divided into two groups according to the median concentration for the controls. Unconditional logistic regression analysis was performed adjusting for sex, age, and body mass index. For several higher chlorinated congeners increased risk was found for patients in the high-concentration and high-titer group. For toxic equivalency factor >27.79 and EA>80 an odds ratio of 2.8 with 95% confidence interval 0.52-18 was calculated. These results indicated that current exposure to certain organochlorines in combination with EBV might increase the risk for NHL.

Medical risk factors for small-bowel adenocarcinoma with focus on Crohn disease: a European population-based case-control study.

BACKGROUND: Crohn disease and biliary diseases have been associated with small-bowel adenocarcinoma (SBA). We examined how medical conditions affect the risk of SBA. METHODS: A population-based European multicentre case-control study during the period 1995-97 including 95 histologically verified cases of SBA along with 3335 population controls; 70 cases (74%) and 2070 (62%) controls were interviewed about previous medical conditions. RESULTS: Crohn disease was identified in two SBA cases (both located in ileum) and two controls; odds ratio (OR) 53.6 (6.0-477) (95% CI in parentheses). Only one case and no controls had had long-standing Crohn disease. Coeliac disease was associated with SBA (2 cases, 0 controls), but one of the cases was diagnosed at the same time as the SBA. Overall, people with a history of gallstones had no increased risk of SBA. The OR was exclusively increased during the 3-year period preceding the SBA diagnosis. Previous gallstone surgery, which may be a sign of severe gallstone disease, was not associated with SBA. Liver cirrhosis, hepatitis or medical treatments with radioactive substances or corticosteroid tablets were not associated with this disease. Cases with SBA had an increased prevalence of anaemia; OR 15.3 (2.5-92.1). An association between low educational level and SBA was found; OR 1.75 (1.0-3.0). CONCLUSION: This study supports Crohn disease and coeliac disease being strong but rare risk factors for SBA. Previous gallstones were unrelated to SBA, and detection bias may account for the findings in earlier studies.

Breast-feeding duration and the risk of malignant diseases in childhood in Sweden.

OBJECTIVE: To evaluate childhood cancer in relation to duration of breast-feeding. SETTING: Sweden. Records from Child Healthcare Centres were scrutinised regarding information on breast-feeding and other health-related items. SUBJECTS: All children aged 0-14 y with a malignant disease (benign brain tumours included) during the time period 1988-91 (n = 962) were identified from the Swedish Cancer Register. An equal number of controls matched for sex and age were selected from the Swedish Birth Register. RESULTS: Information was obtained for 835 cases and 860 controls. Overall, duration of breast-feeding did not influence the risk for a malignant disease in this age group. However, breast-feeding > or = 1 month increased the risk for non-Hodgkin's lymphoma (NHL) yielding an odds ratio (OR) 5.5 with 95% confidence interval (CI) 1.2-25. Breast-feeding 1 -< 6 months gave OR 5.1, CI 1.1-24 and > 6 months gave OR 7.0, CI 1.3-37 with a significant trend (P = 0.04). Adjustment for maternal and birth-related co-variates gave similar results. For other malignancies no significant changes of the risk were obtained. CONCLUSIONS: Overall, no association between duration of breast-feeding and childhood malignancies was found except for a significantly increased risk for NHL, but this was based on low numbers of cases and needs to be confirmed in other investigations.