Late effects, long-term problems and unmet needs of cancer survivors.

Great efforts are being made in cancer treatment, with impressive improvement in survival. The situation concerning research and care for long-term problems and late effects in the growing population of cancer survivors, however, is unsatisfactory. Therefore, in the FiX survey 1348 disease-free survivors about 4 years after diagnosis of different cancer types were asked to rate existing burdens and support received for them along a list of 36 potential problems. Health-related quality of life (HRQoL) was assessed with the EORTC QLQ-C30. Determinants of burdens were explored using logistic regression analysis. While cancer survivors' global HRQoL, physical and role function ratings were comparable or better than age- and sex-matched reference values of the general population, emotional and cognitive function was worse, especially among women (P < .01). Most frequently reported problems with at least moderate burden were loss of physical performance (36.3%), fatigue (35.1%), sexual problems (34.7%), sleep problems (34.1%), arthralgia (33.8%), anxiety (28.0%), neuropathy (25.6%), memory problems (23.0%) and concentration problems (21.9%). Burdened survivors often rated received support as poor, especially regarding support for problems that physicians might consider medically nonthreatening, or for which no effective pharmacologic or medical treatment is known. Determinants for burden included higher age, female gender, having ever received chemotherapy and overweight/obesity. In conclusion, a significant number of cancer survivors suffer from long-term or late effects and have unmet care needs. Awareness of health care professionals should be increased for these issues. The results of our study can contribute to the development of targeted survivorship plans.

Overdiagnosis in lung cancer screening: Estimates from the German Lung Cancer Screening Intervention Trial.

Overdiagnosis is a major potential harm of lung cancer screening; knowing its potential magnitude helps to optimize screening eligibility criteria. The German Lung Screening Intervention Trial ("LUSI") is a randomized trial among 4052 long-term smokers (2622 men), 50.3 to 71.9 years of age from the general population around Heidelberg, Germany, comparing five annual rounds of low-dose computed tomography (n = 2029) with a control arm without intervention (n = 2023). After a median follow-up of 9.77 years postrandomization and 5.73 years since last screening, 74 participants were diagnosed with lung cancer in the control arm and 90 in the screening arm: 69 during the active screening period; of which 63 screen-detected and 6 interval cancers. The excess cumulative incidence in the screening arm (N = 16) represented 25.4% (95% confidence interval: -11.3, 64.3] of screen-detected cancer cases (N = 63). Analyzed by histologic subtype, excess incidence in the screening arm appeared largely driven by adenocarcinomas. Statistical modeling yielded an estimated mean preclinical sojourn time (MPST) of 5.38 (4.76, 5.88) years and a screen-test sensitivity of 81.6 (74.4%, 88.8%) for lung cancer overall, all histologic subtypes combined. Based on modeling, we further estimated that about 48% (47.5% [43.2%, 50.7%]) of screen-detected tumors have a lead time ≥4 years, whereas about 33% (32.8% [28.4%, 36.1%]) have a lead time ≥6 years, 23% (22.6% [18.6%, 25.7%]) ≥8 years, 16% (15.6% [12.2%, 18.3%]) ≥10 years and 11% (10.7% [8.0%, 13.0%]) ≥12 years. The high proportions of tumors with relatively long lead times suggest a major risk of overdiagnosis for individuals with comparatively short remaining life expectancies.

Knowledge, perceptions, and management of cancer-related fatigue: the patients' perspective.

PURPOSE: This study aimed to assess cancer patients' knowledge and perceptions regarding fatigue and to provide up-to-date information on the current fatigue management from the patients' perspective. METHODS: The FiX study recruited 2508 cancer patients approximately 2 years after diagnosis via a cancer registry in Germany. Participants completed a questionnaire on their knowledge and perceptions of fatigue and the management received. RESULTS: More than half of respondents (58%), especially among the elderly patients, did not feel well informed about fatigue. Overall, 41% reported having never been asked about being exhausted by their treating physician. Even fewer patients stated that general practitioners or nurses have asked if they felt exhausted. Only 13% of patients who had experienced severe fatigue had received a fatigue assessment by means of a rating scale or questionnaire-although this is recommended by existing guidelines for fatigue screening. Health care professionals seemed less likely to address fatigue with elderly as well as female patients. The most commonly reported measure against fatigue was exercise or regular physical activity (68%). However, this was mostly done on patients' own initiative. Psychological support was rarely used (13%) and only in approximately half of the cases upon the advice of a physician. Yoga, another promising intervention against fatigue, was performed by only 9% of patients. CONCLUSIONS: Our study indicates deficits in terms of knowledge, education, screening, counseling, and treatment for fatigue and highlights starting points for targeted improvements in fatigue management based on patients' needs.

Change patterns and determinants of physical activity differ between breast, prostate, and colorectal cancer patients.

PURPOSE: The purpose of this study was to examine and compare pre- to post-diagnosis change patterns of physical activity (PA) among breast, prostate, and colorectal cancer patients. Moreover, the study aimed to investigate sociodemographic and medical determinants of post-diagnosis PA and to identify patient subgroups at increased risk of inactivity. METHODS: A total of 912 cancer patients (457 breast, 241 prostate, 214 colorectal cancer) completed a questionnaire assessing their pre- and post-diagnosis PA behavior, and sociodemographic and medical variables. Age-adjusted regression and classification tree analyses were used to investigate PA determinants and detect subgroups that were most likely to meet or not meet PA guidelines. RESULTS: Across cancer types, we found that PA yet decreased from pre- to post-diagnosis, but that 54.1% of participants still reported to be meeting PA guidelines after the diagnosis. While post-diagnosis PA was strongly affected by previous PA behavior among individuals of all patient groups, other sociodemographic and medical determinants played different roles depending on cancer type. The results yielded that previously active, longer diagnosed patients with higher education levels were most likely to be meeting PA guidelines post-diagnosis, whereas specifically previously inactive prostate cancer patients had an increased likelihood of insufficient activity. CONCLUSIONS: An encouragingly high number of cancer patients indicated sufficient PA levels. For those having difficulties to maintain or adopt PA post-diagnosis, interventions should be tailored to the specific characteristics of each cancer type, as different factors are associated with PA for each patient group.

Patient-physician communication about cancer-related fatigue: a survey of patient-perceived barriers.

PURPOSE: Cancer-related fatigue is a subjective, distressing, and common sequela of cancer which is often disregarded and underdiagnosed. Fatigue is assessed by self-report requiring communication between patient and physician. In this study, we investigated the patients' perspective on the patient-physician communication about fatigue. METHODS: On average five months after diagnosis 1179 cancer patients, recruited in Germany, completed a survey as part of the LIFT project. The survey included questions on sociodemographic data, fatigue, depression, fatigue management, patient-physician communication, and communication barriers. Data were analyzed descriptively and using logistic regression analyses. RESULTS: Half of the participants reported that their physician had never asked them whether they felt exhausted. Patients undergoing chemo-, radio-, or immunotherapy were more likely to be asked about fatigue, while older age and major depression decreased the likelihood. Sixty-four percent of the patients felt impeded by communication barriers. Common barriers were not knowing who to turn to for fatigue (39%), time constraints (31%), and the fear of being perceived as weak (22%). Almost half of the participants indicated that their physicians were not appreciative and did not deal adequately with fatigue-related questions. CONCLUSION: This study revealed gaps in the patient-physician communication regarding cancer-related fatigue. Contrary to guideline recommendations a minority of physicians addressed fatigue. On the other hand, cancer patients felt reluctant to bring up this topic due to structural barriers and fears. Physicians should routinely address fatigue and adopt a communication style which encourages patients to likewise state their symptoms and raise their questions. TRIAL REGISTRATION: Clinicaltrials.gov, identifier: NCT04921644. Registered in June 2021.

Characteristics, Treatment Patterns and Survival of International Federation of Gynecology and Obstetrics Stage IV Epithelial Ovarian Cancer-A Population-Based Study.

BACKGROUND: The aim of the present study was to describe an unselected population of patients with diagnosis of FIGO stage IV OC. METHODS: Data from 1183 patients were available for analysis. RESULTS: The majority of patients (962/1183, 81.3%) received cancer-directed treatment. The median follow-up time was 3.8 years, and the median overall survival duration was 1.9 years. Notably, patients >80 years had a low overall survival rate (HR of age >80 years vs. ≤50 years was 3.81, 95%-CI [2.76, 5.27], p < 0.0001). The survival rate was best in patients with HGSOC (p < 0.0001). The highest overall survival rate was observed in patients in the group with surgical intervention followed by systemic treatment, with an unadjusted HR of 0.72, 95%-CI [0.59, 0.86], p = 0.007 vs. systemic treatment only. After adjustment for age and histology, survival differences between treatment schemes were smaller (HR 0.81, 95%-CI [0.66, 1.00], p = 0.12). CONCLUSIONS: In this cohort of patients with FIGO stage IV OC, more than 80% of the patients received cancer-directed treatment. Age and high-grade serous histology were determinants for survival. The highest overall survival rate was observed in patients who underwent surgery followed by systemic treatment.

Phase III study of the European Organisation for Research and Treatment of Cancer Quality of Life cancer survivorship core questionnaire.

PURPOSE: The purpose of this study is to develop a European Organisation for Research and Treatment of Cancer Quality of Life Group (EORTC QLG) questionnaire that captures the full range of physical, mental, and social health-related quality of life (HRQOL) issues relevant to disease-free cancer survivors. In this phase III study, we pretested the provisional core questionnaire (QLQ-SURV111) and aimed to identify essential and optional scales. METHODS: We pretested the QLQ-SURV111 in 492 cancer survivors from 17 countries with one of 11 cancer diagnoses. We applied the EORTC QLG decision rules and employed factor analysis and item response theory (IRT) analysis to assess and, where necessary, modify the hypothesized questionnaire scales. We calculated correlations between the survivorship scales and the QLQ-C30 summary score and carried out a Delphi survey among healthcare professionals, patient representatives, and cancer researchers to distinguish between essential and optional scales. RESULTS: Fifty-four percent of the sample was male, mean age was 60 years, and, on average, time since completion of treatment was 3.8 years. Eleven items were excluded, resulting in the QLQ-SURV100, with 12 functional and 9 symptom scales, a symptom checklist, 4 single items, and 10 conditional items. The essential survivorship scales consist of 73 items. CONCLUSIONS: The QLQ-SURV100 has been developed to assess comprehensively the HRQOL of disease-free cancer survivors. It includes essential and optional scales and will be validated further in an international phase IV study. IMPLICATIONS FOR CANCER SURVIVORS: The availability of this questionnaire will facilitate a standardized and robust assessment of the HRQOL of disease-free cancer survivors.

Effects of phenotypes in heterocyclic aromatic amine (HCA) metabolism-related genes on the association of HCA intake with the risk of colorectal adenomas.

BACKGROUND: Heterocyclic aromatic amines (HCA), formed by high-temperature cooking of meat, are well-known risk factors for colorectal cancer (CRC). Enzymes metabolizing HCAs may influence the risk of CRC depending on the enzyme activity level. We aimed to assess effect modification by polymorphisms in the HCA-metabolizing genes on the association of HCA intake with colorectal adenoma (CRA) risk, which are precursors of CRC. METHODS: A case-control study nested in the EPIC-Heidelberg cohort was conducted. Between 1994 and 2005, 413 adenoma cases were identified and 796 controls were matched to cases. Genotypes were determined and used to predict phenotypes (i.e., enzyme activities). Odds ratios (OR) and corresponding 95 % confidence intervals (CI) were calculated by logistic regression analysis. RESULTS: CRA risk was positively associated with PhIP, MeIQx, and DiMeIQx (p trend = 0.006, 0.022, and 0.045, respectively) intake. SULT1A1 phenotypes modified the effect of MeIQx on CRA risk (p (Interaction) > 0.01) such that the association of MeIQx intake with CRA was stronger for slow than for normal phenotypes. Other modifying effects by phenotypes did not reach statistical significance. CONCLUSIONS: HCA intake is positively associated with CRA risk, regardless of phenotypes involved in the metabolizing process. Due to the number of comparisons made in the analysis, the modifying effect of SULT1A1 on the association of HCA intake with CRA risk may be due to chance.

Determinants of non- response to a second assessment of lifestyle factors and body weight in the EPIC-PANACEA study.

BACKGROUND: This paper discusses whether baseline demographic, socio-economic, health variables, length of follow-up and method of contacting the participants predict non-response to the invitation for a second assessment of lifestyle factors and body weight in the European multi-center EPIC-PANACEA study. METHODS: Over 500.000 participants from several centers in ten European countries recruited between 1992 and 2000 were contacted 2-11 years later to update data on lifestyle and body weight. Length of follow-up as well as the method of approaching differed between the collaborating study centers. Non-responders were compared with responders using multivariate logistic regression analyses. RESULTS: Overall response for the second assessment was high (81.6%). Compared to postal surveys, centers where the participants completed the questionnaire by phone attained a higher response. Response was also high in centers with a short follow-up period. Non-response was higher in participants who were male (odds ratio 1.09 (confidence interval 1.07; 1.11), aged under 40 years (1.96 (1.90; 2.02), living alone (1.40 (1.37; 1.43), less educated (1.35 (1.12; 1.19), of poorer health (1.33 (1.27; 1.39), reporting an unhealthy lifestyle and who had either a low (<18.5 kg/m2, 1.16 (1.09; 1.23)) or a high BMI (>25, 1.08 (1.06; 1.10); especially ≥30 kg/m2, 1.26 (1.23; 1.29)). CONCLUSIONS: Cohort studies may enhance cohort maintenance by paying particular attention to the subgroups that are most unlikely to respond and by an active recruitment strategy using telephone interviews.

The contribution of risk factors to the higher incidence of invasive and in situ breast cancers in women with higher levels of education in the European prospective investigation into cancer and nutrition.

The authors investigated the role of known risk factors in educational differences in breast cancer incidence. Analyses were based on the European Prospective Investigation Into Cancer and Nutrition and included 242,095 women, 433 cases of in situ breast cancer, and 4,469 cases of invasive breast cancer. Reproductive history (age at first full-term pregnancy and parity), exposure to endogenous and exogenous hormones, height, and health behaviors were accounted for in the analyses. Relative indices of inequality (RII) for education were estimated using Cox regression models. A higher risk of invasive breast cancer was found among women with higher levels of education (RII = 1.22, 95% confidence interval (CI): 1.09, 1.37). This association was not observed among nulliparous women (RII = 1.13, 95% CI: 0.84, 1.52). Inequalities in breast cancer incidence decreased substantially after adjusting for reproductive history (RII = 1.11, 95% CI: 0.98, 1.25), with most of the association being explained by age at first full-term pregnancy. Each other risk factor explained a small additional part of the inequalities in breast cancer incidence. Height accounted for most of the remaining differences in incidence. After adjusting for all known risk factors, the authors found no association between education level and risk of invasive breast cancer. Inequalities in incidence were more pronounced for in situ breast cancer, and those inequalities remained after adjustment for all known risk factors (RII = 1.61, 95% CI: 1.07, 2.41), especially among nulliparous women.

The impact of social status inconsistency on cardiovascular risk factors, myocardial infarction and stroke in the EPIC-Heidelberg cohort.

BACKGROUND: Social inequalities in cardiovascular diseases are well documented. Yet, the relation of social status inconsistency (having different ranks in two or more status indicators like education, occupational position or income) and medical conditions of heart or vessels is not clear. Status inconsistency (SI) is assumed to be stressful, and the association of psychosocial distress and health is well known. Therefore, we aimed to analyze the relationship between cardiovascular diseases (CVD) and status inconsistency. Another target was to assess the influence of behaviour related risk factors on this association. METHODS: 8960 men and 6070 women, aged 45-65 years, from the EPIC-Heidelberg cohort (European Prospective Investigation into Cancer and Nutrition) were included. Socio-economic status was assessed by education/vocational training and occupational position at recruitment. During a median follow-up of 8.7 years, information on CVD was collected. RESULTS: Compared to status consistent subjects, men who were in a higher occupational position than could be expected given their educational attainment had a nearly two-fold increased incidence of CVD (Odds Ratio (OR) = 1.8, 95% Confidence Interval (CI) = 1.5; 2.4, adjusted for age). Smoking behaviour and BMI differed significantly between those who had adequate occupational positions and those who did not. Yet, these lifestyle factors, as opposed to age, did not contribute to the observed differences in CVD. No association of cardiovascular diseases and status inconsistency was found for women or in cases where education exceeded occupational position. CONCLUSIONS: Status inconsistent men (occupational position > education) had a higher risk of cardiovascular diseases than status consistent men. However, harmful behaviour did not explain this relationship.

The association of education with body mass index and waist circumference in the EPIC-PANACEA study.

BACKGROUND: To examine the association of education with body mass index (BMI) and waist circumference (WC) in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHOD: This study included 141,230 male and 336,637 female EPIC-participants, who were recruited between 1992 and 2000. Education, which was assessed by questionnaire, was classified into four categories; BMI and WC, measured by trained personnel in most participating centers, were modeled as continuous dependent variables. Associations were estimated using multilevel mixed effects linear regression models. RESULTS: Compared with the lowest education level, BMI and WC were significantly lower for all three higher education categories, which was consistent for all countries. Women with university degree had a 2.1 kg/m2 lower BMI compared with women with lowest education level. For men, a statistically significant, but less pronounced difference was observed (1.3 kg/m2). The association between WC and education level was also of greater magnitude for women: compared with the lowest education level, average WC of women was lower by 5.2 cm for women in the highest category. For men the difference was 2.9 cm. CONCLUSION: In this European cohort, there is an inverse association between higher BMI as well as higher WC and lower education level. Public Health Programs that aim to reduce overweight and obesity should primarily focus on the lower educated population.

Occupational exposures contribute to educational inequalities in lung cancer incidence among men: Evidence from the EPIC prospective cohort study.

The aim of this study is to investigate to what extent occupational exposures may explain socioeconomic inequalities in lung cancer incidence after adjusting for smoking and dietary factors. Analyses were based on a subsample of the European Prospective Investigation into Cancer and Nutrition (EPIC study), a prospective cohort. The analyses included 703 incident lung cancer cases among men in Denmark, the United Kingdom, Germany, Italy, Spain and Greece. The socioeconomic position was measured using the highest level of education. The estimates of relative indices of inequality (RII) were computed with Cox regression models. We first adjusted for smoking (with detailed information on duration and quantity) and dietary factors (fruits and vegetables consumption) and then for occupational exposures. The exposure to three carcinogens [asbestos, heavy metals and polycyclic aromatic hydrocarbons (PAH)] was analyzed. The occupational exposures explained 14% of the socioeconomic inequalities remaining after adjustment for smoking and fruits and vegetables consumption. The inequalities remained nevertheless statistically significant. The RII decreased from 1.87 (95% CI: 1.36-2.56) to 1.75 (1.27-2.41). The decrease was more pronounced when adjusting for asbestos than for heavy metals or PAH. Analyses by birth cohort suggested an effect of occupational exposures among older men, while due to small number of endpoints, no conclusion could be drawn about the role of occupational exposures in educational inequalities among younger men. Our study revealed that the impact of occupational exposures on socioeconomic inequalities in cancer incidence, rarely studied until now, exists while of modest magnitude.

Prevalence and severity of long-term physical, emotional, and cognitive fatigue across 15 different cancer entities.

BACKGROUND: Fatigue prevalence and severity have been assessed in a variety of studies, yet, not in a standardized way, and predominantly in breast cancer patients. Systematic, comparative investigations across a broad range of cancer entities are lacking. METHODS: The FiX study systematically enrolled 2244 cancer patients across 15 entities approximately 2 years after diagnosis. Fatigue was assessed with the multidimensional EORTC QLQ-FA12 questionnaire. Physical, emotional, cognitive, and total fatigue were compared across entities and with normative values of the general population. Differences in patients' characteristics and cancer therapy between entities were taken into account using analyses of covariance models. RESULTS: Across all entities, mean physical fatigue levels were significantly higher than age- and sex-matched means of the general population for all cancer entities (all Bonferroni-Holm adjusted P < .01). For most entities also emotional and cognitive fatigue levels were significantly higher than normative values. Age- and sex-standardized physical fatigue prevalence ranged from 31.8% among prostate to 51.7% among liver cancer patients. Differences between entities could not be fully explained by sex, age, BMI, or cancer therapy. Adjusted for these factors, mean physical fatigue was higher for stomach (P = .0004), lung (P = .034), kidney (P = .0011), pancreas (P = .081), and endometrium (P = .022) compared to breast cancer patients. Adjusted means of emotional fatigue were also lowest in breast cancer patients and significantly higher in stomach (P = .0047), bladder (P = .0036), and rectal (P = .0020) cancer patients. CONCLUSIONS: Physical, emotional, and cognitive fatigue is prevalent in all 15 investigated cancer entities even 2 years after diagnosis. Fatigue in breast cancer patients, the so-far most studied group, is in the lowest range among all entities, suggesting that the extent of fatigue is still insufficiently determined. Entity-specific problems might need to be considered in the treatment of fatigue.

Bacterial cell growth is arrested by violet and blue, but not yellow light excitation during fluorescence microscopy.

BACKGROUND: Fluorescence microscopy is a powerful tool in cell biology, especially for the study of dynamic processes. Intensive irradiation of bacteria with UV, blue and violet light has been shown to be able to kill cells, but very little information is available on the effect of blue or violet light during live-cell imaging. RESULTS: We show here that in the model bacterium Bacillus subtilis chromosome segregation and cell growth are rapidly halted by standard violet (405 nm) and blue light (CFP) (445-457 nm) excitation, whereas they are largely unaffected by green light (YFP). The stress sigma factor σB and the blue-light receptor YtvA are not involved in growth arrest. Using synchronized B. subtilis cells, we show that the use of blue light for fluorescence microscopy likely induces non-specific toxic effects, rather than a specific cell cycle arrest. Escherichia coli and Caulobacter crescentus cells also stop to grow after 15 one-second exposures to blue light (CFP), but continue growth when imaged under similar conditions in the YFP channel. In the case of E. coli, YFP excitation slows growth relative to white light excitation, whereas CFP excitation leads to cell death in a majority of cells. Thus, even mild violet/blue light excitation interferes with bacterial growth. Analyzing the dose-dependent effects of violet light in B. subtilis, we show that short exposures to low-intensity violet light allow for continued cell growth, while longer exposures do not. CONCLUSIONS: Our experiments show that care must be taken in the design of live-cell imaging experiments in that violet or blue excitation effects must be closely controlled during and after imaging. Violet excitation during sptPALM or other imaging studies involving photoactivation has a threshold, below which little effects can be seen, but above which a sharp transition into cell death occurs. YFP imaging proves to be better suited for time-lapse studies, especially when cell cycle or cell growth parameters are to be examined.

Development and proof-of-concept of a multicenter, patient-centered cancer registry for breast cancer patients with metastatic disease-the "Breast cancer care for patients with metastatic disease" (BRE-4-MED) registry.

BACKGROUND: Patients with metastatic breast cancer (MBC) are treated with a palliative approach with focus on controlling for disease symptoms and maintaining high quality of life. Information on individual needs of patients and their relatives as well as on treatment patterns in clinical routine care for this specific patient group are lacking or are not routinely documented in established Cancer Registries. Thus, we developed a registry concept specifically adapted for these incurable patients comprising primary and secondary data as well as mobile-health (m-health) data. METHODS: The concept for patient-centered "Breast cancer care for patients with metastatic disease" (BRE-4-MED) registry was developed and piloted exemplarily in the region of Main-Franconia, a mainly rural region in Germany comprising about 1.3 M inhabitants. The registry concept includes data on diagnosis, therapy, progression, patient-reported outcome measures (PROMs), and needs of family members from several sources of information including routine data from established Cancer Registries in different federal states, treating physicians in hospital as well as in outpatient settings, patients with metastatic breast cancer and their family members. Linkage with routine cancer registry data was performed to collect secondary data on diagnosis, therapy, and progression. Paper and online-based questionnaires were used to assess PROMs. A dedicated mobile application software (APP) was developed to monitor needs, progression, and therapy change of individual patients. Patient's acceptance and feasibility of data collection in clinical routine was assessed within a proof-of-concept study. RESULTS: The concept for the BRE-4-MED registry was developed and piloted between September 2017 and May 2018. In total n = 31 patients were included in the pilot study, n = 22 patients were followed up after 1 month. Record linkage with the Cancer Registries of Bavaria and Baden-Württemberg demonstrated to be feasible. The voluntary APP/online questionnaire was used by n = 7 participants. The feasibility of the registry concept in clinical routine was positively evaluated by the participating hospitals. CONCLUSION: The concept of the BRE-4-MED registry provides evidence that combinatorial evaluation of PROMs, needs of family members, and raising clinical parameters from primary and secondary data sources as well as m-health applications are feasible and accepted in an incurable cancer collective.

Lifestyle factors, obesity and the risk of colorectal adenomas in EPIC-Heidelberg.

OBJECTIVE: We investigated the association of lifestyle and obesity with colorectal adenoma risk in a prospective setting. METHODS: At recruitment (1994-1998), information on diet, anthropometry, lifestyle, and medication was assessed in 25,540 participants of the EPIC-Heidelberg cohort. Until June 2007, 536 verified incident colorectal adenomas were identified. Furthermore, participants with negative colonoscopy (n = 3966) were included in the analytic cohort. RESULTS: In multivariate logistic regression analyses, participants with highest alcohol intake had an increased adenoma risk (odds ratio [OR] = 1.63; 95% CI 1.21-2.22) compared with lowest intake group. Folate consumption modified the ethanol effect (p-interaction = 0.03). Current smokers had a significantly increased adenoma risk compared with never smokers (OR = 1.40; 95% CI 1.16-1.84). Regular NSAID intake was associated with lower risk in subjects who reported their use at least twice compared with nonusers (OR = 0.70; 95% CI 0.53-0.93). Physical activity, body mass index, and waist-to-hip ratio were not consistently associated with adenoma risk. CONCLUSIONS: The results of this prospective cohort study showed that alcohol intake and smoking are important risk factors for colorectal adenoma, and regular NSAID use decreases the risk. The relationship between alcohol consumption and adenoma risk was modified by folate intake. However, we could not confirm an effect of obesity or physical activity on adenoma risk.

The impact of education on risk factors and the occurrence of multimorbidity in the EPIC-Heidelberg cohort.

BACKGROUND: In aging populations, the prevalence of multimorbidity is high, and the role of socioeconomic status and its correlates is not well described. Thus, we investigated the association between educational attainment and multimorbidity in a prospective cohort study, taking also into account intermediate factors that could explain such associations. METHODS: We included 13,781 participants of the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC), who were 50-75 years at the end of follow-up. Information on diet and lifestyle was collected at recruitment (1994-1998). During a median follow-up of 8.7 years, information on chronic conditions and death were collected. RESULTS: Overall, the prevalence of multimorbidity (>= 2 concurrent chronic diseases) was 67.3%. Compared to the highest educational category, the lowest was statistically significantly associated with increased odds of multimorbidity in men (OR = 1.43; 95% CI 1.28-1.61) and women (OR = 1.33; 95% CI 1.18-1.57). After adjustment, the positive associations were attenuated (men: OR = 1.28; 95% CI 1.12-1.46; women: OR = 1.16; 95% CI 0.99-1.36). Increasing BMI was more strongly than smoking status an intermediate factor in the association between education and multimorbidity. CONCLUSION: In this German population, the prevalence of multimorbidity is high and is significantly associated with educational level. Increasing BMI is the most important predictor of this association. However, even the fully adjusted model, i.e. considering also other known risk factors for chronic diseases, could not entirely explain socio-economic inequalities in multimorbidity. Educational level should be considered in the development and implementation of prevention strategies of multimorbidity.

Modification of breast cancer risk in young women by a polymorphic sequence in the egfr gene.

The regulation of the epidermal growth factor receptor (egfr) gene in human cancer is not yet fully understood. Recent data on a polymorphic CA repeat located at the 5'-regulatory sequence in intron 1 of the egfr gene [egfr CA simple sequence repeat (SSR) I] point to a possible inheritance of cancer risk associated with the egfr gene. Furthermore, we have detected frequent allelic imbalances restricted to the egfr CA SSR I in breast cancer tissue and nontumorous breast tissue adjacent to invasive and in situ breast cancer representing amplifications. Therefore, we conducted a population-based case-control study to assess the relationship between the egfr polymorphism and breast cancer risk. Cases with a first primary breast cancer by age 50 years and age-matched population controls provided information on known and suspected risk factors. The allelic length of the egfr CA SSR was determined in 616 cases and 1072 population-sampled controls. Genotypes were categorized for analysis by allele length. Multivariate logistic regression was used to compare genotype distributions, accounting for other risk factors, and to investigate gene-environment interactions. We found a modifying effect, albeit no main effect, of the allelic length of the egfr polymorphism on breast cancer risk. The presence of two long alleles (>/==" BORDER="0">19 CA) was associated with a significantly elevated odds ratio (OR) of 10.4 [95% confidence interval (CI), 1.85-58.70] among women with a first-degree family history of breast cancer (P = 0.015 for interaction). The risk increase associated with high red meat consumption (OR, 10.68; 95% CI, 1.57-72.58) and the protective effect of high vegetable intake (OR, 0.07; 95% CI, 0.004-1.07) was also most pronounced among carriers of two long alleles (>/==" BORDER="0">19 CA). The length of the egfr CA SSR may increase the risk for familial breast cancers, and its effect could be modulated by dietary factors.

Lifestyle determinants and mortality in German vegetarians and health-conscious persons: results of a 21-year follow-up.

BACKGROUND: The long-term observation of vegetarians in affluent countries can provide insight into the relative effects of a vegetarian diet and lifestyle factors on mortality. METHODS: A cohort study of vegetarians and health-conscious persons in Germany was followed-up prospectively for 21 years, including 1,225 vegetarians and 679 health-conscious nonvegetarians. Standardized mortality ratios compared with the German general population were calculated for all causes and specific causes. Within the cohort, Poisson regression modeling was used to investigate the joint effects of several risk factors on overall and cause-specific mortality. RESULTS: Standardized mortality ratios for all-cause mortality was significantly below 100: 59 [95% confidence interval (95% CI), 54-64], predominantly due to a deficit of deaths from circulatory diseases. Within the cohort, vegetarian compared with nonvegetarian diet had no effect on overall mortality [rate ratio (RR), 1.10; 95% CI, 0.89-1.36], whereas moderate and high physical activity significantly reduced risk of death (RR, 0.62, 0.64), adjusted for age, sex, smoking, alcohol intake, body mass index, and educational level. Vegetarian diet was however associated with a reduced RR of 0.70 (95% CI, 0.41-1.18) for ischemic heart disease, which could partly be related to avoidance of meat. CONCLUSIONS: Both vegetarians and nonvegetarian health-conscious persons in this study have reduced mortality compared with the general population. Within the study, low prevalence of smoking and moderate or high level of physical activity but not strictly vegetarian diet was associated with reduced overall mortality. The nonsignificant reduction in mortality from ischemic heart diseases in vegetarians compared with health-conscious persons could be explained in part by avoidance of meat intake.