Physical activity and risk of breast cancer overall and by hormone receptor status: the European prospective investigation into cancer and nutrition.

Physical activity is associated with reduced risks of invasive breast cancer. However, whether this holds true for breast cancer subtypes defined by the estrogen receptor (ER) and the progesterone receptor (PR) status is controversial. The study included 257,805 women from the multinational EPIC-cohort study with detailed information on occupational, recreational and household physical activity and important cofactors assessed at baseline. During 11.6 years of median follow-up, 8,034 incident invasive breast cancer cases were identified. Data on ER, PR and combined ER/PR expression were available for 6,007 (67.6%), 4,814 (54.2%) and 4,798 (53.9%) cases, respectively. Adjusted hazard ratios (HR) were estimated by proportional hazards models. Breast cancer risk was inversely associated with moderate and high levels of total physical activity (HR = 0.92, 95% confidence interval (CI): 0.86-0.99, HR = 0.87, 95%-CI: 0.79-0.97, respectively; p-trend = 0.002), compared to the lowest quartile. Among women diagnosed with breast cancer after age 50, the largest risk reduction was found with highest activity (HR = 0.86, 95%-CI: 0.77-0.97), whereas for cancers diagnosed before age 50 strongest associations were found for moderate total physical activity (HR = 0.78, 95%-CI: 0.64-0.94). Analyses by hormone receptor status suggested differential associations for total physical activity (p-heterogeneity = 0.04), with a somewhat stronger inverse relationship for ER+/PR+ breast tumors, primarily driven by PR+ tumors (p-heterogeneity < 0.01). Household physical activity was inversely associated with ER-/PR- tumors. The results of this largest prospective study on the protective effects of physical activity indicate that moderate and high physical activity are associated with modest decreased breast cancer risk. Heterogeneities by receptor status indicate hormone-related mechanisms.

Physical activity and endogenous sex hormones in postmenopausal women: to what extent are observed associations confounded or modified by BMI?

OBJECTIVES: To investigate associations between physical activity and endogenous sex hormones after menopause with a special focus on confounding and effect modification by body mass index (BMI). METHODS: A cross-sectional study among 1,260 postmenopausal women was conducted. Generalized linear models were used to compare levels of total leisure-time physical activity, sports activities, bicycling, and walking with levels of sex hormones and sex-hormone-binding-globulin (SHBG). RESULTS: Higher sports activity levels were significantly associated with lower levels of estrone and total and free testosterone in multivariate adjusted models. After additional adjustment for BMI, associations with estrone and free testosterone were attenuated; the association with total testosterone remained unchanged. No physical activity variable was significantly related to total and free estradiol, androstenedione, or SHBG. We did not observe effect modification by BMI. CONCLUSIONS: Sports activities may lead to lower levels of estrone and testosterone in postmenopausal women. While effects on estrone and free testosterone seem to be largely mediated by BMI, effects on total testosterone appear to be mainly independent of BMI. The BMI-independent effects on these hormones (especially on total testosterone) could at least partly explain why physical activity has been frequently reported to be preventive for postmenopausal breast cancer, even after accounting for BMI.

Birth defects in the vicinity of nuclear power plants in Germany.

Living in the vicinity of nuclear power plants (NPP) is discussed here in terms of adverse health effects. A prospective population-based cohort study was conducted to evaluate whether the prevalence of birth defects in the vicinity of NPPs is elevated and scrutinize a possible distance correlation. A birth cohort born to mothers living within 10 km of two selected NPPs (study region) was compared to a region without NPP (comparison region), and an active surveillance of all live births, stillbirths, and induced abortions in the defined regions was performed. Between 01/2007 and 02/2008, all newborns were examined by specially trained study paediatricians according to the protocols of the Birth Registry Mainz Model. The cohort consisted of 5,273 infants (90% completeness). The outcome measure was an infant with birth defect(s). The prevalence of infants with birth defects was 4.5% in the study region and 4.7% in the comparison region, which corresponds to a relative risk (RR) of 0.94 (lower 95% confidence level (CL): 0.76). Thus, the prevalence of birth defects in the regions surrounding NPPs was not increased compared to those of the comparison region. Adjustment for potential confounders did not substantially change the result (RR 0.90, lower 95% CL 0.73). The adjusted and unadjusted distance approach (1/distance in km) did not show any correlation to vicinity to a NPP (p = 0.38). Specifically, within the study region, the prevalence of birth defects showed no upward trend with decreasing distance. Birth defect prevalence and most descriptive parameters in the comparison region were identical to those in the Birth Registry Mainz Model.

History of allergic disease and epilepsy and risk of glioma and meningioma (INTERPHONE study group, Germany).

The aim of the present analysis was to examine the association of a medical history of asthma, hay fever, eczema, or epilepsy with the risk of glioma and meningioma. Data of a German population-based case-control study included 381 meningioma cases, 366 glioma cases, and 1,494 controls. Participants' histories of asthma, hay fever, eczema, and epilepsy and the respective ages at onset were asked during a personal interview. A small inverse association between allergic condition and both glioma (odds ratio: 0.92; 95% CI: 0.70-1.22) and meningioma (odd ratio: 0.87; 95% CI: 0.66-1.14) was found. For glioma, this inverse association was more pronounced in persons reporting to have asthma compared to other allergic conditions. The positive association between epilepsy and particularly glioma suggests that epilepsy is an early symptom of the disease. As the association was seen also for epilepsies occurring more than a decade before the diagnosis of glioma, this might indicate either an aetiological role of epilepsy, or a relatively long preclinical phase. In conclusion our study confirms previous findings of case control studies but not those from cohort studies. However, possible selection bias in case control studies might not explain the different results in its entirety.

Feasibility of a cohort study on health risks caused by occupational exposure to radiofrequency electromagnetic fields.

BACKGROUND: The aim of this study was to examine the feasibility of performing a cohort study on health risks from occupational exposure to radiofrequency electromagnetic fields (RF-EMF) in Germany. METHODS: A set of criteria was developed to evaluate the feasibility of such a cohort study. The criteria aimed at conditions of exposure and exposure assessment (level, duration, preferably on an individual basis), the possibility to assemble a cohort and the feasibility of ascertaining various disease endpoints. RESULTS: Twenty occupational settings with workers potentially exposed to RF-EMF and, in addition, a cohort of amateur radio operators were considered. Based on expert ratings, literature reviews and our set of predefined criteria, three of the cohorts were identified as promising for further evaluation: the personnel (technicians) of medium/short wave broadcasting stations, amateur radio operators, and workers on dielectric heat sealers. After further analyses, the cohort of workers on dielectric heat sealers seems not to be feasible due to the small number of exposed workers available and to the difficulty of assessing exposure (exposure depends heavily on the respective working process and mixture of exposures, e.g. plastic vapours), although exposure was highest in this occupational setting. The advantage of the cohort of amateur radio operators was the large number of persons it includes, while the advantage of the cohort of personnel working at broadcasting stations was the quality of retrospective exposure assessment. However, in the cohort of amateur radio operators the exposure assessment was limited, and the cohort of technicians was hampered by the small number of persons working in this profession. CONCLUSION: The majority of occupational groups exposed to RF-EMF are not practicable for setting up an occupational cohort study due to the small numbers of exposed subjects or due to exposure levels being only marginally higher than those of the general public.

Radiofrequency electromagnetic fields emitted from base stations of DECT cordless phones and the risk of glioma and meningioma (Interphone Study Group, Germany).

The objective of this study was to test the hypothesis that exposure to continuous low-level radiofrequency electromagnetic fields (RF EMFs) increases the risk of glioma and meningioma. Participants in a population-based case-control study in Germany on the risk of brain tumors in relation to cellular phone use were 747 incident brain tumor cases between the ages of 30 and 69 years and 1494 matched controls. The exposure measure of this analysis was the location of a base station of a DECT (Digital Enhanced Cordless Telecommunications) cordless phone close to the bed, which was used as a proxy for continuous low-level exposure to RF EMFs during the night. Estimated odds ratios were 0.82 (95% confidence interval: 0.29-2.33) for glioma and 0.83 (0.29-2.36) for meningioma. There was also no increasing risk observed with duration of exposure to DECT cordless phone base stations. Although the study was limited due to the small number of exposed subjects, it is still a first indication that residential low-level exposure to RF EMFs may not pose a higher risk of brain tumors.

[Protective effects of physical activity in the occurrence of colon cancer]. / Rola aktywnosci fizycznej w zapobieganiu zachorowaniom na raka jelita grubego.

The purpose of the study was to assess the role of occupational and leisure physical activity on the risk pattern of colon cancer considering the possible confounding effects of dietary habits. Case-control study has been carried out in 180 incident cases of colon cancer hospitalized in Chair of Surgery CMUJ in Kraków. The equal number of controls individually matched by gender and age were chosen amongst patients with no history of cancer from the university hospital. Food frequency questionnaire combined with quantity of foods eaten was used to assess the usual dietary patterns for 148 food items. The occupational physical activity of the interviewed subjects before the occurrence of the disease was assessed by self-rating. Leisure time activity was measured by the number of hours watching TV. The adjusted risk of colon cancer was reduced by half in those being active in leisure time (OR = 0.56, 95% CI: 0.32-0.98). The effect of occupational physical activity had the same order of magnitude in terms of risk reduction (OR = 0.56; 95% CI: 0.28-1.10). The protective effect of healthy nutrition appeared to be independent from that attributed to physical effort.

Evaluation of a short retrospective questionnaire for physical activity in women.

Physical activity (PA) is discussed as a preventive factor for many chronic diseases. Thus, in epidemiological studies it often is an important covariate. Due to frequently long latency periods, long-term PA in the past is of greater interest than current PA. However, there is a lack of retrospective questionnaires that are validated for long-term PA, including occupational, household, and leisure activities. We therefore evaluated a short questionnaire for the comprehensive assessment of usual PA in distant age periods, administered with cognitive interviewing techniques. From an ongoing study on postmenopausal breast cancer 110 cases and 101 controls, age 50-74 years, were randomly selected. Our questionnaire was administered in a telephone interview more than two months after the main study interview, which included a detailed questionnaire on PA performed in the age periods 30-49 years and 50+ years. Total PA scores were derived from both interviews as MET-hours per week. Degree of agreement was assessed using Bland-Altman analyses. Further, potential sources of systematic and random error were investigated. The mean difference between both questionnaires was 3 MET hours/week, and 53.6% of absolute differences were below 35 MET hours/week, i.e. showing good agreement. Further 28.9% of differences could be considered acceptable agreement. Measurement errors seem to be non-differential with respect to cancer status. The median interviewing time was 10 min. Overall, this short questionnaire appears to be a useful and valid tool to distinguish between high and low levels of women's physical activity in the distant past.

Cellular phones, cordless phones, and the risks of glioma and meningioma (Interphone Study Group, Germany).

The widespread use of cellular telephones has generated concern about possible adverse health effects, particularly brain tumors. In this population-based case-control study carried out in three regions of Germany, all incident cases of glioma and meningioma among patients aged 30-69 years were ascertained during 2000-2003. Controls matched on age, gender, and region were randomly drawn from population registries. In total, 366 glioma cases, 381 meningioma cases, and 1,494 controls were interviewed. Overall use of a cellular phone was not associated with brain tumor risk; the respective odds ratios were 0.98 (95% confidence interval (CI): 0.74, 1.29) for glioma and 0.84 (95% CI: 0.62, 1.13) for meningioma. Among persons who had used cellular phones for 10 or more years, increased risk was found for glioma (odds ratio = 2.20, 95% CI: 0.94, 5.11) but not for meningioma (odds ratio = 1.09, 95% CI: 0.35, 3.37). No excess of temporal glioma (p = 0.41) or meningioma (p = 0.43) was observed in cellular phone users as compared with nonusers. Cordless phone use was not related to either glioma risk or meningioma risk. In conclusion, no overall increased risk of glioma or meningioma was observed among these cellular phone users; however, for long-term cellular phone users, results need to be confirmed before firm conclusions can be drawn.

Occupational exposure to radio frequency/microwave radiation and the risk of brain tumors: Interphone Study Group, Germany.

It is still under debate whether occupational exposure to radio frequency/microwave electromagnetic fields (RF/MW-EMF) contributes to the development of brain tumors. This analysis examined the role of occupational RF/MW-EMF exposure in the risk of glioma and meningioma. A population-based, case-control study including 381 meningioma cases, 366 glioma cases, and 1,494 controls aged 30-69 years was performed in three German regions in 2000-2003. An exposure matrix for occupational activity was constructed by using information on RF/MW-EMF exposure collected in a computer-assisted personal interview. "High" exposure was defined as an occupational exposure that may exceed the RF/MW-EMF exposure limits for the general public recommended by the International Commission on Non-Ionizing Radiation Protection. Multiple conditional logistic regressions were performed separately for glioma and meningioma. No significant association between occupational exposure to RF/MW-EMF and brain tumors was found. For glioma, the adjusted odds ratio for highly exposed persons compared with persons not highly exposed was 1.21 (95% confidence interval: 0.69, 2.13); for meningioma, it was 1.34 (95% confidence interval: 0.64, 2.81). However, the slight increase in risk observed with increasing duration of exposure merits further research with larger sample sizes.

A pooled analysis of bladder cancer case-control studies evaluating smoking in men and women.

OBJECTIVE: A recent study suggested that risk of bladder cancer may be higher in women than in men who smoked comparable amounts of cigarettes. We pooled primary data from 14 case-control studies of bladder cancer from Europe and North America and evaluated differences in risk of smoking by gender. METHODS: The pooled analysis included 8316 cases (21% women) and 17,406 controls (28% women) aged 30-79 years. Odds ratios (ORs) and 95% confidence intervals (95% CI) for smoking were adjusted for age and study. Exposure-response was evaluated in a stratified analysis by gender and by generalized additive models. RESULTS: The odds ratios for current smokers compared to nonsmokers were 3.9 (95% CI 3.5-4.3) for males and 3.6 (3.1-4.1) for females. In 11 out of 14 studies, ORs were slightly higher in men. ORs for current smoking were similar for men (OR = 3.4) and women (OR = 3.7) in North America, while in Europe men (OR = 5.3) had higher ORs than women (OR = 3.9). ORs increased with duration and intensity in both genders and the exposure-response patterns were remarkably similar between genders. CONCLUSION: These results do not support the hypothesis that women have a higher relative risk of smoking-related bladder cancer than men.

Occupational risk factors for low grade and high grade glioma: results from an international case control study of adult brain tumours.

The majority of suspected occupational risk factors for adult brain tumours have yet to be confirmed as etiologically relevant. Within an international case-control study on brain tumours, lifelong occupational histories and information on exposures to specific substances were obtained by direct interviews to further investigate occupational risk factors for glioma. This is one of the largest studies of brain tumours in adults, including 1,178 cases and 1987 population controls from 8 collaborating study centres matched for age, gender and centre. All occupational information, was aggregated into 16 occupational categories. In a pooled analysis, odds ratios (OR), adjusted for education, were estimated separately for men and women and for high-grade glioma (HGG) and low-grade glioma (LGG), focusing especially on 6 categories defined a priori: agricultural, chemical, construction, metal, electrical/electronic and transport. For men, an elevated OR of glioma associated with the category "metal" (OR = 1.24, 95% CI 0.96-1.62) was seen, which appeared to be largely accounted for by LGG (OR = 1.59, 95% CI 1.00-2.52). For the other 5 occupational categories, no elevated risks for glioma were observed. For women the only noteworthy observation for the 6 a priori categories was an inverse association with the "agriculture" category (OR = 0.60, 95% CI 0.36-0.99). Apart from the 6 major categories, women working in food production or food processing (category "food") showed an increased OR of 1.95 (95% CI 1.04-3.68). None of the 20 substance groups was positively associated with glioma risk. Although some other point estimates were elevated, they lacked statistical significance. The results do not provide evidence of a strong association between occupational exposures and glioma development.

Linear regression calibration: theoretical framework and empirical results in EPIC, Germany.

Large scale dietary assessment instruments are usually based on the food frequency technique and have therefore to be tailored to the involved populations with respect to mode of application and inquired food items. In multicenter studies with different populations, the direct comparability of dietary data is therefore a challenge because each local dietary assessment tool might have its specific measurement error. Thus, for risk analysis the direct use of dietary measurements across centers requires a common reference. For example, in the European prospective cohort study EPIC (European Prospective Investigation into Cancer and Nutrition) a 24-hour recall was chosen to serve as such a reference instrument which was based on a highly standardized computer-assisted interview (EPIC-SOFT). The 24-hour recall was applied to a representative subset of EPIC participants in all centers. The theoretical framework of combining multicenter dietary information was previously published in several papers and is called linear regression calibration. It is based on a linear regression of the food frequency questionnaire to the reference. The regression coefficients describe the absolute and proportional scaling bias of the questionnaire with the 24-hour recall taken as reference. This article describes the statistical basis of the calibration approach and presents first empirical results of its application to fruit, cereals and meat consumption in EPIC Germany represented by the two EPIC centers, Heidelberg and Potsdam. It was found that fruit could be measured well by the questionnaire in both centers (lambdacirc; = 0.98 (males) and lambdacirc; = 0.95 (females) in Heidelberg, and lambdacirc; = 0.86 (males) and lambdacirc; = 0.7 (females) in Potsdam), cereals less (lambdacirc; = 0.53 (males) and lambdacirc; = 0.4 (females) in Heidelberg, and lambdacirc; = 0.53 (males) and lambdacirc; = 0.44 (females) in Potsdam), and that the assessment of meat (lambdacirc; = 0.72 (males) and lambdacirc; = 0.65 (females) in Heidelberg, and lambdacirc; = 0.49 (males) and lambdacirc; = 0.42 (females) in Potsdam) has a center-specific bias. The application of the calibration approach to the questionnaire data will change the ranking of the two centers following the data of the reference instrument, and not well-measured food items will exhibit considerably less variation compared to the original data. We conclude that calibration is a necessary step in multicenter studies. However, this exercise shows that the current statistical framework is not yet sufficiently developed for a broad application.

Alcohol consumption and the risk of colorectal cancer at low levels of micronutrient intake.

BACKGROUND: The purpose of our study was to assess the relationship between simultaneous exposure to alcohol and consumption of micronutrients that may have protective properties against colorectal cancer. MATERIAL/METHODS: This hospital-based case-control study of colorectal cancer was carried out between January 1998 and November 1999 in Cracow, Poland. A total of 180 cases of colorectal cancer confirmed by histopathology were recruited from the University Hospital in Cracow. An equal number of controls, individually matched by gender and age (+/- 5 years) were chosen from among patients from the same hospital with no history of cancer. An interviewer-administered food frequency questionnaire covering 148 food items, including the quantity consumed, was used to assess the typical dietary pattern. RESULTS: When the analysis was carried out on quartile intake data, a consistent inverse association was confirmed between the intake of retinol, thiamine or antioxidant micronutrients (carotene, vitamin C and E) and the occurrence of colorectal cancer. Alcohol intake appeared to be an important risk factor for this cancer site, and the risk increased with the amount of pure alcohol intake. The group with deficient intake of retinol, carotene, and vitamins C and E, but with higher consumption of alcohol, incur a noticeably high risk of colorectal cancer (OR=6.79; 95%CI: 2.08-22.18). CONCLUSIONS: The data support the hypothesis that higher consumption of alcohol, when combined with low micronutrient intake, may considerably increase the risk of colorectal cancer.

Occupation and bladder cancer among men in Western Europe.

OBJECTIVES: We examined which occupations and industries are currently at high risk for bladder cancer in men. METHODS: We combined data from 11 case-control studies conducted between 1976-1996 in six European countries. The study comprised 3346 incident cases and 6840 controls, aged 30-79 years. Lifetime occupational and smoking histories were examined using common coding. RESULTS: Odds ratios for eight a priori defined high-risk occupations were low, and with the exception of metal workers and machinists (OR = 1.16, 95% CI = 1.02-1.32), were not statistically significant. Higher risks were observed for specific categories of painters, metal, textile and electrical workers, for miners, transport operators, excavating-machine operators, and also for non-industrial workers such as concierges and janitors. Industries entailing a high risk included salt mining, manufacture of carpets, paints, plastics and industrial chemicals. An increased risk was found for exposure to PAHs (OR for highest exposure tertile = 1.23, 95% CI = 1.07-1.4). The risk attributable to occupation ranged from 4.2 to 7.4%, with an estimated 4.3% for exposure to PAHs. CONCLUSIONS: Metal workers, machinists, transport equipment operators and miners are among the major occupations contributing to occupational bladder cancer in men in Western Europe. In this population one in 10 to one in 20 cancers of the bladder can be attributed to occupation.