Temporal association between childhood leukaemia and population growth in Swiss municipalities.

The population mixing hypothesis proposes that childhood leukaemia (CL) might be a rare complication of a yet unidentified subclinical infection. Large population influxes into previously isolated rural areas may foster localised epidemics of the postulated infection causing a subsequent increase of CL. While marked population growth after a period of stability was central to the formulation of the hypothesis and to the early studies on population mixing, there is a lack of objective criteria to define such growth patterns. We aimed to determine whether periods of marked population growth coincided with increases in the risk of CL in Swiss municipalities. We identified incident cases of CL aged 0-15 years for the period 1985-2010 from the Swiss Childhood Cancer Registry. Annual data on population counts in Swiss municipalities were obtained for 1980-2010. As exposures, we defined (1) cumulative population growth during a 5-year moving time window centred on each year (1985-2010) and (2) periods of 'take-off growth' identified by segmented linear regression. We compared CL incidence across exposure categories using Poisson regression and tested for effect modification by degree of urbanisation. Our study included 1500 incident cases and 2561 municipalities. The incident rate ratio (IRR) comparing the highest to the lowest quintile of 5-year population growth was 1.18 (95 % CI 0.96, 1.46) in all municipalities and 1.33 (95 % CI 0.93, 1.92) in rural municipalities (p value interaction 0.36). In municipalities with take-off growth, the IRR comparing the take-off period (>6 % annual population growth) with the initial period of low or negative growth (<2 %) was 2.07 (95 % CI 0.95, 4.51) overall and 2.99 (1.11, 8.05) in rural areas (p interaction 0.52). Our study provides further support for the population mixing hypothesis and underlines the need to distinguish take-off growth from other growth patterns in future research

Calibration adjustments to address bias in mortality analyses due to informative sampling—a census-linked survey analysis in Switzerland

Background Sampling bias, like survey participants’ nonresponse, needs to be adequately addressed in the analysis of sampling designs. Often survey weights will be calibrated on specific covariates related to the probability of selection and nonresponse to get representative population estimates. However, such calibrated survey (CS) weights are usually constructed for cross-sectional results, but not for longitudinal analyses. For example, when the outcome of interest is time to death, and sampling selection is related to time to death and censoring, sampling is informative. Then, unweighted or CS weighted inferential statistical analyses may be biased. In 2010, Switzerland changed from a decennial full enumeration census to a yearly registry-based (i.e., data from harmonised community registries) and a survey-based census system. In the present study, we investigated the potential bias due to informative sampling when time to death is the outcome of interest, using data from the new Swiss census system. Methods We analysed more than 6.5 million individuals aged 15 years or older from registry-based census data from years 2010 to 2013, linked with mortality records up to end of 2014. Out of this population, a target sample of 3.5% was sampled from the Swiss Federal Statistical Office (SFSO) in a stratified yearly micro census. The SFSO calculated CS weights to enable representative population estimates from the micro census. We additionally constructed inverse probability (IP) weights, where we used survival information in addition to known sampling covariates. We compared CS and IP weighted mortality rates (MR) and life expectancy (LE) with estimates from the underlying population. Additionally, we performed a simulation study under different sampling and nonresponse scenarios. Results We found that individuals who died in 2011, had a 0.67 (95% CI [0.64–0.70]) times lower odds of participating in the 2010 micro census, using a multivariable logistic regression model with covariates age, gender, nationality, civil status, region and survival information. IP weighted MR were comparable to estimates from the total population, whereas CS weighted MR underestimated the population MR in general. The IP weighted LE estimates at age 30 years for men were 50.9 years (95% CI [50.2–51.6] years), whereas the CS weighted overestimated LE by 2.5 years. Our results from the simulation study confirmed that IP weighted models are comparable to population estimates. Conclusion Mortality analyses based on the new Swiss survey-based census system may be biased, because of informative sampling. We conclude that mortality analyses based on census-linked survey data have to be carefully conducted, and if possible, validated by registry information to allow for unbiased interpretation and generalisation

Space-time clustering of childhood cancers in Switzerland: A nationwide study

The aetiology of childhood cancers remains largely unknown. It has been hypothesized that infections may be involved and that mini-epidemics thereof could result in space-time clustering of incident cases. Most previous studies support spatio-temporal clustering for leukaemia, while results for other diagnostic groups remain mixed. Few studies have corrected for uneven regional population shifts which can lead to spurious detection of clustering. We examined whether there is space-time clustering of childhood cancers in Switzerland identifying cases diagnosed at age 0.2). Our study suggests that childhood leukaemia tends to cluster in space-time due to an etiologic factor present in early life

Space-Time Clustering of Childhood Leukemia: Evidence of an Association with ETV6-RUNX1 (TEL-AML1) Fusion

BACKGROUND: Many studies have observed space-time clustering of childhood leukemia (CL) yet few have attempted to elicit etiological clues from such clustering. We recently reported space-time clustering of CL around birth, and now aim to generate etiological hypotheses by comparing clustered and nonclustered cases. We also investigated whether the clustering resulted from many small aggregations of cases or from a few larger clusters. METHODS: We identified cases of persons born and diagnosed between 1985 and 2014 at age 0-15 years from the Swiss Childhood Cancer Registry. We determined spatial and temporal lags that maximized evidence of clustering based on the Knox test and classified cases born within these lags from another case as clustered. Using logistic regression adjusted for child population density, we determined whether clustering status was associated with age at diagnosis, immunophenotype, cytogenetic subtype, perinatal and socioeconomic characteristics, and pollution sources. RESULTS: Analyses included 1,282 cases of which 242 were clustered (born within 1 km and 2 years from another case). Of all investigated characteristics only the t(12;21)(p13;q22) translocation (resulting in ETV6-RUNX1 fusion) differed significantly in prevalence between clustered and nonclustered cases (40% and 25%, respectively; adjusted OR 2.54 [1.52-4.23]; p = 0.003). Spatio-temporal clustering was driven by an excess of aggregations of two or three children rather than by a few large clusters. CONCLUSION: Our findings suggest ETV6-RUNX1 is associated with space-time clustering of CL and are consistent with an infection interacting with that oncogene in early life leading to clinical leukemia

Adherence to the cancer prevention recommendations of the World Cancer Research Fund/American Institute for Cancer Research and mortality: a census-linked cohort

BACKGROUND Modifiable lifestyle factors linked to cancer offer great potential for prevention. Previous studies suggest an association between adherence to recommendations on healthy lifestyle and cancer mortality. OBJECTIVES The aim of this study was to examine whether adherence to the cancer prevention recommendations of the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) is associated with reduced all-cause, total cancer, and specific cancer type mortality. DESIGN We built a lifestyle score that included 3 categories, based on the recommendations of the WCRF/AICR. Applying Cox regression models, we investigated the association with all-cause, total cancer, and specific cancer type mortality; in addition, we included cardiovascular disease (CVD) mortality. We used census- and death registry-linked survey data allowing a mortality follow-up for ≤32 y. Our analysis included 16,722 participants. Information on lifestyle score components and confounders was collected at baseline. RESULTS Over a mean follow-up of 21.7 y, 3730 deaths were observed (1332 cancer deaths). Comparing best with poorest category of the lifestyle score showed an inverse association with all-cause (HR: 0.82; 95% CI: 0.75, 0.89) and total cancer (men only, HR: 0.69; 95% CI: 0.57, 0.84) mortality. We estimated that ∼13% of premature cancer deaths in men would have been preventable if lifestyle score levels had been high. Inverse associations were observed for lung, upper aerodigestive tract, stomach, and prostate cancer mortality [men and women combined, HR: 0.72; 95% CI: 0.51, 0.99; HR: 0.49; 95% CI: 0.26, 0.92; HR: 0.34; 95% CI: 0.14, 0.83; HR: 0.48; 95% CI: 0.28, 0.82 (men only), respectively]. CVD mortality was not associated with the lifestyle score (men and women combined, HR: 0.96; 95% CI: 0.82, 1.13). CONCLUSIONS Our results support the importance of adhering to recommendations for a healthy lifestyle with regard to all-cause and cancer mortality. To reduce the burden of cancer in the population, preventive measures should stress the potential of low-risk health behavior patterns rather than of specific risk factors only

Aircraft noise, air pollution, and mortality from myocardial infarction

OBJECTIVE: Myocardial infarction has been associated with both transportation noise and air pollution. We examined residential exposure to aircraft noise and mortality from myocardial infarction, taking air pollution into account. METHODS:: We analyzed the Swiss National Cohort, which includes geocoded information on residence. Exposure to aircraft noise and air pollution was determined based on geospatial noise and airpollution (PM10) models and distance to major roads. We used Cox proportional hazard models, with age as the timescale. We compared the risk of death across categories of A-weighted sound pressure levels (dB(A)) and by duration of living in exposed corridors, adjusting for PM10 levels, distance to major roads, sex, education, and socioeconomic position of the municipality. RESULTS:: We analyzed 4.6 million persons older than 30 years who were followed from near the end of 2000 through December 2005, including 15,532 deaths from myocardial infarction (ICD-10 codes I 21, I 22). Mortality increased with increasing level and duration of aircraft noise. The adjusted hazard ratio comparing 45 dB(A) was 1.3 (95% confidence interval = 0.96-1.7) overall, and 1.5 (1.0-2.2) in persons who had lived at the same place for at least 15 years. None of the other endpoints (mortality from all causes, all circulatory disease, cerebrovascular disease, stroke, and lung cancer) was associated with aircraft noise. CONCLUSION:: Aircraft noise was associated with mortality from myocardial infarction, with a dose-response relationship for level and duration of exposure. The association does not appear to be explained by exposure to particulate matter air pollution, education, or socioeconomic status of the municipality

Marital status, living arrangement and mortality : does the association vary by gender?

Background Men appear to benefit more from being married than women with respect to mortality in middle age. However, there is some uncertainty about gender differences in mortality risks in older individuals, widowed, divorced and single individuals and about the impact of living arrangements. Methods Longitudinal data with 1990 census records being linked to mortality data up to 2005 were used (Swiss National Cohort). The sample comprised all residents over age 44 years in Switzerland (n=2 440 242). All-cause mortality HRs for marital status and living arrangements were estimated by Cox regression for men and women and different age groups with adjustment for education and socio-professional category. Results The benefit of being married was stronger for men than for women; however, mortality patterns were similar, with higher mortality in divorced and single individuals compared with widowed individuals (>80 years). After adjustment for living arrangements, the gender difference by marital status disappeared. Stratification by living arrangement revealed that mortality risks were highest for 45-64-year-old divorced (HR 1.72 (95% CI 1.67 to 1.76)) and single men (HR 1.67 (95% CI 1.63 to 1.71)) who lived alone. In women of the same age, the highest mortality risk was observed for those who were single and living with a partner (HR 1.70 (95% CI 1.58 to 1.82)). In older age groups, the impact of marital status decreased. Conclusions Evaluation of living arrangements is crucial for identifying and explaining gender differences in mortality risks by marital status. The impact of living alone and living with a partner seems to be different in men and wome

Dietary Patterns Are Associated with Cardiovascular and Cancer Mortality among Swiss Adults in a Census-Linked Cohort

Defining dietary guidelines requires a quantitative assessment of the influence of diet on the development of diseases. The aim of the study was to investigate how dietary patterns were associated with mortality in a general population sample of Switzerland. We included 15,936 participants from two population-based studies (National Research Program 1A (NRP1A) and Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA)-1977 to 1993) who fully answered a simplified 24-h dietary recall. Mortality data were available through anonymous record linkage with the Swiss National Cohort (follow-up of up to 37.9 years). Multiple correspondence analysis and hierarchical clustering were used to define data-driven qualitative dietary patterns. Mortality hazard ratios were calculated for all-cause, cancer and cardiovascular mortality using Cox regression. Two patterns were characterized by a low dietary variety ("Sausage and Vegetables", "Meat and Salad"), two by a higher variety ("Traditional", "High-fiber foods") and one by a high fish intake ("Fish"). Males with unhealthy lifestyle (smokers, low physical activity and high alcohol intake) were overrepresented in the low-variety patterns and underrepresented in the high-variety and "Fish" patterns. In multivariable-adjusted models, the "Fish" (hazard ratio = 0.82, 95% CI (0.68-0.99)) and "High-fiber foods" (0.85 (0.72-1.00)) patterns were associated with lower cancer mortality. In men, the "Fish" (0.73 (0.55-0.97)) and "Traditional" (0.76 (0.59-0.98)) patterns were associated with lower cardiovascular mortality. In summary, our results support the notion that dietary patterns affect mortality and that these patterns strongly cluster with other health determinants