Breast cancer incidence and mammography screening among resettlers in Germany.

BACKGROUND: European studies showed that women with a migration background are less likely to participate in mammography screenings than autochthonous women. However, the participation in the German mammography screening programme (MSP) among ethnic German migrants from countries of the former Soviet Union (called resettlers) is unclear so far. The aim of this study was to identify possible differences regarding MSP participation between resettlers from the FSU and the general German population. METHODS: Data from two independent, complementary studies from North Rhine-Westphalia, Germany (a retrospective cohort study 1994-2013; a cross-sectional study 2013/14) were used for comparisons between resettlers and the general population: Odds Ratios (ORs) for MSP participation utilizing the cross-sectional data and time trends of breast cancer incidence rates as well as Chi-Square tests for breast cancer stages utilizing the cohort data. RESULTS: Resettlers showed higher Odds to participate in the MSP than the general population (OR 2.42, 95% CI 1.08-5.42). Among resettlers, a large increase in incidence rates was observed during the MSP implementation (2005-2009), resulting in stable and comparable incidence rates after the implementation. Furthermore, pre-MSP implementation, the proportion of advanced breast cancer stages was higher among resettlers than in the German population, post-MSP implementation the proportion was comparable. CONCLUSIONS: MSP participating seems surprisingly high among resettlers. An explanation for the increased willingness to participate might be the structured invitation procedure of the MSP. However, the exact reasons remain unclear and future research is needed to confirm this hypothesis and rule out the possibility of selection bias in the cross-sectional study.

A cross-national perspective of migration and cancer: incidence of five major cancer types among resettlers from the former Soviet Union in Germany and ethnic Germans in Russia.

BACKGROUND: Few studies compared cancer incidence among migrants both to their host countries and to their population of origin. We aimed to compare cancer incidence of ethnic Germans who migrated from the former Soviet Union to Germany (resettlers) to those living in Russia as well as to the German and the Russian general populations. METHODS: The cancer registry of North Rhine-Westphalia identified incident cases of stomach, colorectal, lung, breast and prostate cancer in resettlers and the general population of the administrative district of Münster (Germany) between 2004 and 2013. The Tomsk cancer registry collected the same data in ethnic Germans and the general population of the Tomsk region (Russia). We used standardised incidence rate ratios (SIRs) to compare rates of resettlers and ethnic Germans with the respective general populations. RESULTS: The total number of person-years under risk was 83,289 for ethnic Germans, 8,006,775 for the population of Tomsk, 219,604 for resettlers, and 20,516,782 for the population of Münster. Incidence of the five investigated cancer types among ethnic Germans did not differ from incidence of the general population of Tomsk. Compared to the general population of Tomsk, incidence among resettlers was higher for colorectal cancer in both sexes (females: SIR 1.45 [95% CI 1.14-1.83], males: SIR 1.56 [95% CI 1.23-1.97]), breast cancer in females (SIR 1.65 [95% CI 1.40-1.95]), and prostate cancer (SIR 1.64 [95% CI 1.34-2.01]). Incidence rates of these cancer types among resettlers were more similar to rates of the general population of Münster. Incidence of stomach and lung cancer did not differ between resettlers and the general population of Tomsk. CONCLUSIONS: After an average stay of 15 years, we observed that incidence of colorectal, breast and prostate cancer among resettlers converged to levels of the general population of Münster. Resettler's incidence of stomach and lung cancer, however, was comparable to incidence in their population of origin. Causes must be investigated in subsequent analytical studies.

Development of breast cancer mortality considering the implementation of mammography screening programs - a comparison of western European countries.

BACKGROUND: Triggered by the successive implementation of organized mammography screening programs (MSPs) throughout western European countries over the last decades, there is an ongoing debate questioning their effectiveness. Since it is difficult to assess the effect of MSPs on a population level, we rather aim to assess the impact of the implementation itself on breast cancer mortality rates utilizing an ecological study design. METHODS: We analyzed age group-specific (50-59, 60-69 and 70-79 years) female breast cancer mortality rates in 14 western European countries between 1980 and 2017 using Joinpoint regression, interrupted time series (ITS) regression and multivariable Poisson regression. RESULTS: The Joinpoint analysis demonstrated decreasing trends resulting in annual percentage changes ranging from - 1.5% to - 5.4% (50-59), - 0.2% to - 8.1% (60-69) and 0% to - 7.1% (70-79) depending on the country within 3 years after MSP implementation. The ITS analysis results in highly significant interaction terms (calendar year * binary MSP indicator) for all age groups. The multivariable regression using "calendar year", "year of MSP implementation" and "years with MSP" as independent variables yielded a significant yearly decrease for "years with MSP" ranging from 0.9 to 1.2%. CONCLUSIONS: The results of this study suggest a positive association between the implementation of MSPs and the (accelerated) reduction of breast cancer mortality rates. Measuring and quantifying the isolated effect of MSPs on a population level will require additional studies using individual data.

Time trends of cause-specific mortality among resettlers in Germany, 1990 through 2009.

Resettlers (in German: (Spät-)Aussiedler) form one of the biggest migrant groups in Germany. It is known that migrants have different mortality patterns compared to the autochthon population. In this paper, we combined data from three resettler cohorts and examined differences in mortality from non-communicable diseases among resettlers in Germany and the German population. Furthermore, we investigated time trends of cause-specific mortality for 20 years of follow-up and compared it with the German mortality rates. To assess differences in cause-specific mortality between resettlers and the general German population, we calculated standardized mortality ratios (SMRs). To ascertain mortality trends, cause-specific age-standardized mortality rates were calculated and modeled with Poisson regression and fractional polynomials. During the observation period, the study population accumulated almost 800,000 person-years and 5572 deaths were observed. All-cause mortality among resettlers was lower (SMR = 0.91, 95% CI = 0.89-0.94) compared to the general German population, as well as cardiovascular diseases (CVD) mortality (SMR = 0.82, 95% CI = 0.79-0.86). Results for cancer mortality varied considerably by cancer site. Analyses of time trends showed that all-cause and CVD mortality were decreasing over time in resettlers, as well as in the general German population. Lower all-cause mortality among resettlers is mainly explained by lower CVD mortality. Cancer-site specific mortality showed different results. Converging mortality rates may indicate an adaption of lifestyle behavior. However, there are no data on individual risk factors in this study.

Comparison of female breast cancer between Russia and Germany: A population-based study on time trends and stage at diagnosis.

OBJECTIVES: While a mammography-screening program (MSP) is being offered systematically in Germany since 2009, the dispanserizatsiya has been implemented in Russia since 2013. This study examined trends of stage at breast cancer diagnosis in two Russian regions and compared the results with the development in Germany. In addition, we aimed to gain further insights into the early detection of breast cancer in Russia. METHODS: Incidence data from two cancer registries in Russia and 12 population-based cancer registries in Germany were used to analyse breast cancer incidence rates among women above age 30 over time. Further, we calculated rate ratios to compare the age group-specific incidence rates after the implementation of MSP in Germany (2010-2014) with the period before implementation (2003-2005) separately for each tumour stage and all stages combined. RESULTS: During the study period from 2003 to 2014, age-standardised rates for breast cancer were 54.6 and 116.7 per 100,000 for Russia and Germany, respectively. The proportion of the T1 stage at diagnosis among Russian women aged 50 + is half than that in Germany. Nevertheless, we observed an increasing trend of early-stage alongside the reduction of advanced-stage incidence rates of breast cancer in Russia. CONCLUSIONS: The observed trend in Russia may reflect overall positive changes in early detection of breast cancer, with actual proportion of T1 stage still far behind Germany. Advances in breast cancer screening efforts through the dispanserizatsiya may help to further reduce the breast cancer burden.

Colorectal Cancer among Resettlers from the Former Soviet Union and in the General German Population: Clinical and Pathological Characteristics and Trends.

This study examined time trends and clinical and pathological characteristics of colorectal cancer (CRC) among ethnic German migrants from the Former Soviet Union (resettlers) and the general German population. Incidence data from two population-based cancer registries were used to analyze CRC as age-standardized rates (ASRs) over time. The respective general populations and resettler cohorts were used to calculate standardized incidence ratios (SIRs) by time-period (before and after the introduction of screening colonoscopy in 2002), tumor location, histologic type, grade, and stage at diagnosis. Additionally, SIRs were modeled with Poisson regression to depict time trends. During the study period from 1990 to 2013, the general populations showed a yearly increase of ASR, but for age above 55, truncated ASR started to decline after 2002. Among resettlers, 229 CRC cases were observed, resulting in a lowered incidence for all clinical and pathological characteristics compared to the general population (overall SIR: 0.78, 95% CI 0.68-0.89). Regression analysis revealed an increasing SIR trend after 2002. Population-wide CRC incidence decreases after the introduction of screening colonoscopy. In contrast the lowered CRC incidence among resettlers is attenuating to the general population after 2002, suggesting that resettlers do not benefit equally from screening colonoscopy.

The Incidence of Intestinal Gastric Cancer among Resettlers in Germany-Do Resettlers Remain at an Elevated Risk in Comparison to the General Population?

OBJECTIVE: Previous studies have shown that the incidence of gastric cancer (GC), and particularly intestinal GC, is higher among resettlers from the former Soviet Union (FSU) than in the general German population. Our aim was to investigate if the higher risk remains over time. METHODS: GC cases between 1994 and 2013, in a cohort of 32,972 resettlers, were identified by the respective federal cancer registry. Age-standardized rates (ASRs) and standardized incidence ratios (SIRs) were analyzed in comparison to the general population for GC subtypes according to the Laurén classification. Additionally, the cohort was pooled with data from a second resettler cohort from Saarland to investigate time trends using negative binomial regression. RESULTS: The incidence of intestinal GC was elevated among resettlers in comparison to the general population (SIR (men) 1.64, 95% CI: 1.09-2.37; SIR (women) 1.91, 95% CI: 1.15-2.98). The analysis with the pooled data confirmed an elevated SIR, which was stable over time. CONCLUSION: Resettlers' higher risk of developing intestinal GC does not attenuate towards the incidence in the general German population. Dietary and lifestyle patterns might amplify the risk of GC, and we believe that further investigation of risk behaviors is needed to better understand the development of disease pattern among migrants.

Aussiedler Mortality (AMOR): cohort studies on ethnic German migrants from the Former Soviet Union.

PURPOSE: The Aussiedler Mortality cohorts represent the unique migrant group of ethnic Germans (resettlers) from the former Soviet Union who migrated to Germany mainly after the fall of the iron curtain in 1989. Resettlers are the second largest migrant group in Germany and their health status was largely unknown before the cohorts were set up. PARTICIPANTS: Four retrospective register-based cohorts were set up in different federal states of Germany, each focussing on different health aspects. In total, the cohorts include 92 362 resettlers (men: 51.5%, women: 48.5%) who immigrated between 1990 and 2005 with a mean age at immigration of 36.6 years (range 0-105 years). Resettlers are of German ancestry and they are immediately granted the German citizenship with all rights and duties. FINDINGS TO DATE: Vital status and causes of death (International Classification of Diseases codes based on death certificates or record linkage) were collected for three cohorts as well as cancer incidence and incidence of acute myocardial infarction in three of the cohorts. Currently, an observation period of 20 years (1990-2009) is covered. Overall mortality among resettlers was surprisingly lower in comparison to the German population with standardised mortality ratios of 0.87 (95% confidence limits 0.84-0.91) for women and 0.96 (0.92-0.99) for men, and even stronger for cardiovascular diseases (women: 0.84 (0.79-0.89); men: 0.80 (0.75-0.86). However, observed differences can neither be explained by the 'healthy migrant effect' nor by common behavioural risk factors and may be related to factors which have not yet been studied. FUTURE PLANS: The existing cohorts will be continued and prospective studies on resettlers are underway: one cohort will be followed-up prospectively and two other large prospective cohort studies in Germany will be used for a detailed assessment of lifestyle, environmental and genetic/epigenetic factors on the mortality and morbidity pattern of resettlers.

DNA methylation at an enhancer of the three prime repair exonuclease 2 gene (TREX2) is linked to gene expression and survival in laryngeal cancer.

BACKGROUND: Genetic aberrations in DNA repair genes are linked to cancer, but less is reported about epigenetic regulation of DNA repair and functional consequences. We investigated the intragenic methylation loss at the three prime repair exonuclease 2 (TREX2) locus in laryngeal (n = 256) and colorectal cancer cases (n = 95) and in pan-cancer data from The Cancer Genome Atlas (TCGA). RESULTS: Significant methylation loss at an intragenic site of TREX2 was a frequent trait in both patient cohorts (p = 0.016 and < 0.001, respectively) and in 15 out of 22 TCGA studies. Methylation loss correlated with immunohistochemically staining for TREX2 (p < 0.0001) in laryngeal tumors and improved overall survival of laryngeal cancer patients (p = 0.045). Chromatin immunoprecipitation, demethylation experiments, and reporter gene assays revealed that the region of methylation loss can function as a CCAAT/enhancer binding protein alpha (CEBPA)-responsive enhancer element regulating TREX2 expression. CONCLUSIONS: The data highlight a regulatory role of TREX2 DNA methylation for gene expression which might affect incidence and survival of laryngeal cancer. Altered TREX2 protein levels in tumors may affect drug-induced DNA damage repair and provide new tailored therapies.

Cancer Incidence and Mortality Among Ethnic German Migrants From the Former Soviet Union.

Germany is a country known for immigration. In 2015, 21% of the general population in Germany consisted of individuals with a migration background. This article focuses on cancer-specific incidence and mortality among one of the biggest migrant groups in Germany: the resettlers. Resettlers are ethnic Germans who mainly immigrated from the Russian federation and other countries of the former Soviet Union after its collapse in 1989. We investigated differences between resettlers and the general German population, regarding (i) incidence and mortality of malignant neoplasms, (ii) time trends of the corresponding incidence and mortality, and (iii) cancer stage at diagnosis. We provide data from two resettler cohorts covering an observation time of 20 years: one cohort on cancer incidence (N = 32,972), and another cohort on mortality (N = 59,390). Cancer-specific standardized incidence ratios (SIR) and standardized mortality ratios (SMR) for all malignant neoplasms combined and the most common cancer-sites were calculated between resettlers and the general German population. Time trend analyses using Poisson regression were performed to investigate the developments of SIRs and SMRs. To investigate differences in stage at diagnosis, logistic regression was performed, calculating Odds Ratios for condensed cancer stages. We observed higher incidence and mortality of stomach cancer [SIR (men) 1.62, 95%CI 1.17-2.19; SMR (men) 1.62, 95%CI 1.31-2.01; SIR (women) 1.32, 95%CI 0.86-1.94; SMR (women) 1.52, 95%CI 1.19-1.93] and higher mortality of lung cancer [SMR (men) 1.34, 95%CI 1.20-1.50] among resettlers compared to the general German population, but lower incidence and mortality of colorectal (both sexes), lung (women), prostate and female breast cancer. However, time trend analyses showed converging incidence risks of cause-specific incidence over time, whereas differences of mortality did not show changes over time. Results from logistic regression suggest that resettler men were more often diagnosed with advanced cancer stages compared to the Münster population. Our findings suggest that risk factor patterns of the most common cancer-sites among resettlers are similar to those observed within the Russian population. Such increases in prostate, colorectal and breast cancer incidence may be the consequence of improved detection measures, and/or the adaptation of resettlers to the German lifestyle.

Migration pattern and mortality of ethnic German migrants from the former Soviet Union: a cohort study in Germany.

OBJECTIVE: We aimed to investigate all-cause and cause-specific mortality among ethnic German migrants from the former Soviet Union by different immigration periods to describe associations with migration pattern and mortality. DESIGN: We used pooled data from three retrospective cohort studies in Germany. PARTICIPANTS: Ethnic German migrants from the former Soviet Union (called resettlers), who immigrated to Germany since 1990 to the federal states North Rhine-Westphalia and Saarland and to the region of Augsburg (n=59 390). OUTCOME: All-cause and cause-specific mortality among resettlers in comparison to the general German population, separated by immigration period. METHODS: Immigration periods were defined following legislative changes in German immigration policy (1990-1992, 1993-1995, 1996+). Resettlers' characteristics were described accordingly. To investigate mortality differences by immigration period, we calculated age-standardised mortality rates (ASRs) and standardised mortality ratios (SMRs) of resettlers in comparison to the general German population. Additionally, we modelled sex-specific ASRs with Poisson regression, using age, year and immigration period as independent variables. RESULTS: The composition of resettlers differed by immigration period. Since 1993, the percentage of resettlers from the Russian Federation and non-German spouses increased. Higher all-cause mortality was found among resettlers who immigrated in 1996 and after (ASR 628.1, 95% CI 595.3 to 660.8), compared with resettlers who immigrated before 1993 (ASR 561.8, 95% CI 537.2 to 586.4). SMR analysis showed higher all-cause mortality among resettler men from the last immigration period compared with German men (SMR 1.11, 95% CI 1.04 to 1.19), whereas resettlers who immigrated earlier showed lower all-cause mortality. Results from Poisson regression, adjusted for age and year, corroborated those findings. CONCLUSIONS: Mortality differences by immigration period suggest different risk-factor patterns and possibly deteriorated integration opportunities. Health policy should guard the consequences of immigration law alterations with respect to changing compositions of migrant groups and their health status.

Knowledge about mammography screening in Germany by education and migrant status ­ results of a cross-sectional study (InEMa)

Background: The population-based mammography screening program (MSP) is aimed to reduce breast cancer mortality, to detect breast cancer at an early stage, and to allow for less invasive treatment. However, it also has some potential harms, such as overdiagnosis and overtreatment. Therefore, it is necessary that women receive sufficient and balanced information to enable informed decision-making. We examined knowledge about benefits and harms of the MSP in Germany among first-time invitees of different socio-demographic backgrounds. Methods: This observational study assessed knowledge about benefits and harms of the MSP among women who were invited to the MSP for the first time by six multiple choice items, using a postal survey. We investigated (i) single items of knowledge, (ii) the distribution of sufficient knowledge stratified by education, migration status and invitation, and (iii) possible determinants of sufficient knowledge by analyzing Odds Ratios (ORs) using bivariate and multivariate logistic regression. Results: In total, 5397 women included in the analyses. 46.1% of the study population had sufficient knowledge about benefits and harms of the MSP. However, women with low educational level and migration background had higher proportions of insufficient knowledge and used most frequently the option "don't know". Women had the most difficulties answering the numeric question and the question about the target group correctly. Results from the logistic regression showed that the odds of having sufficient knowledge were higher among well-educated women (OR 3.84, 95%CI 3.24­4.55), among women who already received the MSP invitation (OR 1.38, 95%CI 1.20­1.59) and lowest among Turkish women (OR 0.14, 95%CI 0.07­0.25). Conclusions: Women with low education and migration background need adapted information regarding benefits and harms of the MSP and are important target groups for further developing the information material about mammography screening to reduce disparities in knowledge and enable informed decision-making (AU)