Strong associations of a healthy lifestyle with all stages of colorectal carcinogenesis: Results from a large cohort of participants of screening colonoscopy.

The risk of developing colorectal cancer (CRC) is associated with a wide range of dietary and lifestyle factors. The individual contribution of single modifiable factors, such as alcohol consumption, physical activity, smoking, body mass index (BMI) or dietary components, to the development of CRC has been investigated extensively, but evidence on their combined effect at various stages of colorectal carcinogenesis is sparse. The aim of our study was to analyze the association of a healthy lifestyle pattern with prevalence of early and advanced colorectal neoplasms. A total of 13,600 participants of screening colonoscopy in Saarland/Germany (mean age 62.9 years) who were enrolled in the KolosSal study (Effektivität der Früherkennungs-Koloskopie: eine Saarland-weite Studie) from 2005 until 2013 were included in this cross-sectional analysis. Dietary and lifestyle data were collected and colonoscopy results were extracted from physicians' reports. The association of an a priori defined healthy lifestyle score-including dietary intake, alcohol consumption, physical activity, smoking and BMI-with early and advanced colorectal neoplasms was assessed by multiple logistic regression analyses with comprehensive adjustment for potential confounders. Strong inverse dose-response relationships were observed between an overall healthier lifestyle pattern and presence of advanced colorectal neoplasms, nonadvanced adenomas and hyperplastic polyps (p value <0.0001 in all cases), with adjusted odds ratios (95% CI) for the highest compared to the lowest category of the healthy lifestyle score of 0.41 (0.30-0.56), 0.42 (0.33-0.54) and 0.39 (0.29-0.54) respectively. A healthy lifestyle is strongly associated with lower risk of all stages of colorectal neoplasms.

Utilization and determinants of follow-up colonoscopies within 6 years after screening colonoscopy: Prospective cohort study.

Previous studies have reported that repeat colonoscopies were often not conducted in the recommended time interval after screening colonoscopy. We prospectively followed participants of screening colonoscopy from Germany for 6 years to investigate utilization and determinants of repeat colonoscopies. In a longitudinal study on the effectiveness of screening colonoscopy in the state of Saarland (Germany), participants who had a screening colonoscopy between 2005 and 2007 were contacted by mail 6 years after screening and requested to fill in a standardized questionnaire on utilization of repeat colonoscopies. For all colonoscopies reported, colonoscopy and histology reports were requested from the physician(s). Of 6,407 screening participants, 2,212 (35%) have utilized another colonoscopy. Among participants with negative findings at screening (no adenomas), 962 (22%) had a subsequent colonoscopy within 6 years from screening, accounting for 43% of all patients with a repeat colonoscopy. Family history of CRC and detection of hyperplastic polyps were found to be determinants of higher repeat colonoscopy use. As many as 44% of the participants with low-risk adenomas (N = 509) and 39% with high-risk adenomas (N = 290) at screening did not utilize surveillance colonoscopy within 6 years. Utilization was better with higher school education, prior cancer screening participation and if high-risk adenomas were detected, lower among current smokers and lowest among participants ≥70 years. New strategies will be required considering determinants of adherence to avoid unnecessary colonoscopies and to improve utilization of surveillance according to recommended time intervals among patients at higher risk of CRC in the future.

Risk of loco-regional recurrence and distant metastases of patients with invasive breast cancer up to ten years after diagnosis - results from a registry-based study from Germany.

BACKGROUND: Population-based estimates of the long-term risk of loco-regional recurrence and distant metastases of breast cancer (BRC) patients are scant, as most published studies used hospital-based cohorts or participants of clinical trials. This work aims to extend available knowledge by providing population-based long-term estimates of the cumulative risk of BRC recurrence up to 10 years after diagnosis. METHODS: Data from the population-based Saarland Cancer Registry were used and included 9359 female patients with primary invasive BRC diagnosed between 1999 and 2009. Estimates of the cumulative incidence (CI) of BRC recurrence were derived for patients who had received local surgery with free resection margins by type of recurrence and stratified by age, tumor characteristics and major treatment options, taking into account mortality from any cause as a competing risk. RESULTS: The 10-year CI of BRC recurrence was 16%. For loco-regional recurrence and distant metastases alone it was 8 and 11%, respectively. The estimates showed substantial variation and were particularly increased if tumors were advanced (T1/2N+ 23%, T3/4N0 24%, T3/4N+ 34%), of high grade (23%), or of 'HER2/neu positive' (28%) or 'triple negative' subtype (23%), respectively. CONCLUSIONS: The derived estimates reflect the risk of 'real world' patients and may therefore extend available knowledge. These data are thus of great relevance for clinicians, their patients and researchers. The study likewise demonstrated the usefulness of cancer registries for a population-based monitoring of the effectiveness of cancer care in terms of disease recurrence as a major treatment related outcome measure.

Etiology of hormone receptor positive breast cancer differs by levels of histologic grade and proliferation.

Limited epidemiological evidence suggests that the etiology of hormone receptor positive (HR+) breast cancer may differ by levels of histologic grade and proliferation. We pooled risk factor and pathology data on 5,905 HR+ breast cancer cases and 26,281 controls from 11 epidemiological studies. Proliferation was determined by centralized automated measures of KI67 in tissue microarrays. Odds ratios (OR), 95% confidence intervals (CI) and p-values for case-case and case-control comparisons for risk factors in relation to levels of grade and quartiles (Q1-Q4) of KI67 were estimated using polytomous logistic regression models. Case-case comparisons showed associations between nulliparity and high KI67 [OR (95% CI) for Q4 vs. Q1 = 1.54 (1.22, 1.95)]; obesity and high grade [grade 3 vs. 1 = 1.68 (1.31, 2.16)] and current use of combined hormone therapy (HT) and low grade [grade 3 vs. 1 = 0.27 (0.16, 0.44)] tumors. In case-control comparisons, nulliparity was associated with elevated risk of tumors with high but not low levels of proliferation [1.43 (1.14, 1.81) for KI67 Q4 vs. 0.83 (0.60, 1.14) for KI67 Q1]; obesity among women ≥50 years with high but not low grade tumors [1.55 (1.17, 2.06) for grade 3 vs. 0.88 (0.66, 1.16) for grade 1] and HT with low but not high grade tumors [3.07 (2.22, 4.23) for grade 1 vs. 0.85 (0.55, 1.30) for grade 3]. Menarcheal age and family history were similarly associated with HR+ tumors of different grade or KI67 levels. These findings provide insights into the etiologic heterogeneity of HR+ tumors.

Dietary patterns and risk of advanced colorectal neoplasms: A large population based screening study in Germany.

Specific components of the diet such as red and processed meat have been associated with the risk of developing colorectal cancer. However, evidence on the association of dietary patterns with colorectal neoplasms is sparse. The aim of this study was to analyze the association of dietary patterns with prevalence of advanced colorectal neoplasms among older adults in Germany. A cross-sectional study was conducted among participants of screening colonoscopy in Saarland, Germany, who were enrolled in the KolosSal study (Effektivität der Früherkennungs-Koloskopie: eine Saarland-weite Studie) from 2005 to 2013. Information on diet and lifestyle factors was obtained through questionnaires and colonoscopy results were extracted from physicians' reports. Associations of a priori defined dietary patterns (vegetarian or adapted versions of the Healthy Eating Index [HEI] and the Dietary Approaches to Stop Hypertension [DASH] index) with the risk of advanced colorectal neoplasms were assessed by multiple logistic regression analyses with comprehensive adjustment for potential confounders. A total of 14,309 participants were included (1561 with advanced colorectal neoplasms). Healthier eating behavior was associated with lower prevalence of advanced colorectal neoplasms in a dose-response manner. Adjusted odds ratios (95% confidence intervals) comparing the highest with the lowest categories of adapted HEI and DASH were 0.61 (0.50, 0.76) and 0.70 (0.55, 0.89), respectively. No significant associations were observed for a vegetarian eating pattern (adjusted OR 0.80 (0.55, 1.17)). Healthy dietary patterns, as described by a high HEI or DASH score, but not a vegetarian diet alone, are associated with reduced risk of advanced colorectal neoplasms.

Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2.

We recently identified a novel susceptibility variant, rs865686, for estrogen-receptor positive breast cancer at 9q31.2. Here, we report a fine-mapping analysis of the 9q31.2 susceptibility locus using 43 160 cases and 42 600 controls of European ancestry ascertained from 52 studies and a further 5795 cases and 6624 controls of Asian ancestry from nine studies. Single nucleotide polymorphism (SNP) rs676256 was most strongly associated with risk in Europeans (odds ratios [OR] = 0.90 [0.88-0.92]; P-value = 1.58 × 10(-25)). This SNP is one of a cluster of highly correlated variants, including rs865686, that spans ∼14.5 kb. We identified two additional independent association signals demarcated by SNPs rs10816625 (OR = 1.12 [1.08-1.17]; P-value = 7.89 × 10(-09)) and rs13294895 (OR = 1.09 [1.06-1.12]; P-value = 2.97 × 10(-11)). SNP rs10816625, but not rs13294895, was also associated with risk of breast cancer in Asian individuals (OR = 1.12 [1.06-1.18]; P-value = 2.77 × 10(-05)). Functional genomic annotation using data derived from breast cancer cell-line models indicates that these SNPs localise to putative enhancer elements that bind known drivers of hormone-dependent breast cancer, including ER-α, FOXA1 and GATA-3. In vitro analyses indicate that rs10816625 and rs13294895 have allele-specific effects on enhancer activity and suggest chromatin interactions with the KLF4 gene locus. These results demonstrate the power of dense genotyping in large studies to identify independent susceptibility variants. Analysis of associations using subjects with different ancestry, combined with bioinformatic and genomic characterisation, can provide strong evidence for the likely causative alleles and their functional basis.

Prognostic value of automated KI67 scoring in breast cancer: a centralised evaluation of 8088 patients from 10 study groups.

BACKGROUND: The value of KI67 in breast cancer prognostication has been questioned due to concerns on the analytical validity of visual KI67 assessment and methodological limitations of published studies. Here, we investigate the prognostic value of automated KI67 scoring in a large, multicentre study, and compare this with pathologists' visual scores available in a subset of patients. METHODS: We utilised 143 tissue microarrays containing 15,313 tumour tissue cores from 8088 breast cancer patients in 10 collaborating studies. A total of 1401 deaths occurred during a median follow-up of 7.5 years. Centralised KI67 assessment was performed using an automated scoring protocol. The relationship of KI67 levels with 10-year breast cancer specific survival (BCSS) was investigated using Kaplan-Meier survival curves and Cox proportional hazard regression models adjusted for known prognostic factors. RESULTS: Patients in the highest quartile of KI67 (>12 % positive KI67 cells) had a worse 10-year BCSS than patients in the lower three quartiles. This association was statistically significant for ER-positive patients (hazard ratio (HR) (95 % CI) at baseline = 1.96 (1.31-2.93); P = 0.001) but not for ER-negative patients (1.23 (0.86-1.77); P = 0.248) (P-heterogeneity = 0.064). In spite of differences in characteristics of the study populations, the estimates of HR were consistent across all studies (P-heterogeneity = 0.941 for ER-positive and P-heterogeneity = 0.866 for ER-negative). Among ER-positive cancers, KI67 was associated with worse prognosis in both node-negative (2.47 (1.16-5.27)) and node-positive (1.74 (1.05-2.86)) tumours (P-heterogeneity = 0.671). Further classification according to ER, PR and HER2 showed statistically significant associations with prognosis among hormone receptor-positive patients regardless of HER2 status (P-heterogeneity = 0.270) and among triple-negative patients (1.70 (1.02-2.84)). Model fit parameters were similar for visual and automated measures of KI67 in a subset of 2440 patients with information from both sources. CONCLUSIONS: Findings from this large-scale multicentre analysis with centrally generated automated KI67 scores show strong evidence in support of a prognostic value for automated KI67 scoring in breast cancer. Given the advantages of automated scoring in terms of its potential for standardisation, reproducibility and throughput, automated methods appear to be promising alternatives to visual scoring for KI67 assessment.

Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium.

Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) = 1.04-1.10, P = 2.9 × 10(-6)], AKAP9-M463I at 7q21 (rs6964587, OR = 1.05, 95% CI = 1.03-1.07, P = 1.7 × 10(-6)) and NEK10-L513S at 3p24 (rs10510592, OR = 1.10, 95% CI = 1.07-1.12, P = 5.1 × 10(-17)). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR = 1.07 (95% CI = 1.05-1.10, P = 1.0 × 10(-8)); for AKAP9-M463I, OR = 1.05 (95% CI = 1.04-1.07, P = 2.0 × 10(-10)). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act.

Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors.

Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity) in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene-environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction = 2.4 × 10(-6)) and between CASP8-rs17468277 and alcohol consumption (Pinteraction = 3.1 × 10(-4)). Overall, the per-allele odds ratio (95% confidence interval) for LSP1-rs3817198 was 1.08 (1.01-1.16) in nulliparous women and ranged from 1.03 (0.96-1.10) in parous women with one birth to 1.26 (1.16-1.37) in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85-0.98) in those with an alcohol intake of <20 g/day and 1.45 (1.14-1.85) in those who drank ≥ 20 g/day. Additionally, interaction was found between 1p11.2-rs11249433 and ever being parous (Pinteraction = 5.3 × 10(-5)), with a per-allele OR of 1.14 (1.11-1.17) in parous women and 0.98 (0.92-1.05) in nulliparous women. These data provide first strong evidence that the risk of breast cancer associated with some common genetic variants may vary with environmental risk factors.

Identification of new genetic susceptibility loci for breast cancer through consideration of gene-environment interactions.

Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G × E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714 in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 × 10(-07)), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8,891 postmenopausal women, were identified by all methods applied. SNP rs10483028 was associated with breast cancer in women with a BMI below 25 kg/m(2) (OR = 1.26, 95% CI 1.15-1.38) but not in women with a BMI of 30 kg/m(2) or higher (OR = 0.89, 95% CI 0.72-1.11, P for interaction = 3.2 × 10(-05)). Our findings confirm comparable power of the recent methods for detecting G × E interaction and the utility of using G × E interaction analyses to identify new susceptibility loci.

Prediction of individual genetic risk to prostate cancer using a polygenic score.

BACKGROUND: Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate cancer risk at a genome-wide significant level will improve disease prediction. METHODS: We built polygenic risk scores in a large training set comprising over 25,000 individuals. Initially 65 established prostate cancer susceptibility variants were selected. After LD pruning additional variants were prioritized based on their association with prostate cancer. Six-fold cross validation was performed to assess genetic risk scores and optimize the number of additional variants to be included. The final model was evaluated in an independent study population including 1,370 cases and 1,239 controls. RESULTS: The polygenic risk score with 65 established susceptibility variants provided an area under the curve (AUC) of 0.67. Adding an additional 68 novel variants significantly increased the AUC to 0.68 (P = 0.0012) and the net reclassification index with 0.21 (P = 8.5E-08). All novel variants were located in genomic regions established as associated with prostate cancer risk. CONCLUSIONS: Inclusion of additional genetic variants from established prostate cancer susceptibility regions improves disease prediction.

Risk of contralateral second primary breast cancer according to hormone receptor status in Germany.

INTRODUCTION: Hormone receptor (HR) status has become an established target in treatment strategies of breast cancer. Population-based estimates of contralateral breast cancer (CBC) incidence by HR subtype in particular are limited. The aim of this study was to provide detailed data on CBC incidence for Germany. METHODS: Invasive breast cancer data were extracted on 49,804 women yielding 594 second primaries from the cancer registries of the Federal States of Brandenburg and Saarland and the area of Munich for the period from 1998 to 2007. Multiple imputation was used on missing values for HR status. We estimated standardized incidence ratios (SIRs) with 95% confidence intervals (95%CIs). RESULTS: SIR estimates of CBC among women diagnosed with an invasive first primary breast cancer (FBC) of any HR subtype ranged from 1.0 to 1.5 in the three registries. Pooling three registries' data, the SIR of HR-positive CBC was 0.7 (95%CI: 0.6 to 0.8) among women with HR-positive FBC. For those women with HR-negative FBC, the SIR of HR-negative CBC was 8.9 (95%CI: 7.1 to 11.1). Among women with FBC diagnosed before the age of 50 years, incidence of CBC was increased, especially for HR-negative FBC (SIR: 9.2; 95%CI: 7.1 to 11.9). CONCLUSIONS: HR status of the first primary and age at first diagnosis is relevant for predicting risk of CBC. Particularly, patients with HR-negative FBC had elevated risks.

Quality of life in long-term breast cancer survivors - a 10-year longitudinal population-based study.

BACKGROUND: Breast cancer survivors may experience adverse effects of cancer and/or treatment years after completion of therapy, which can considerably decrease quality of life (QoL). Little is known about the time course of QoL in breast cancer survivors beyond the fifth year post-diagnosis, when routine follow-up care has usually terminated. We therefore explored in detail whether and to what extent restrictions in breast cancer survivors persist and whether changes or aggravations in QoL occurred over time. MATERIAL AND METHODS: QoL was assessed 1, 3, 5, and 10 years post-diagnosis in a population-based cohort of initially 387 female breast cancer patients from Saarland (Germany), using the EORTC QLQ-C30 and QLQ-BR23. Time course of QoL over 10 years post-diagnosis was assessed for survivors and survivors' QoL was compared cross-sectionally to the German general population after adjustment for age. RESULTS: A total of 182 out of 238 patients alive (76.5%) responded in the 10-year, 160 patients (67.2%) participated in all follow-ups. Although breast cancer survivors and controls reported comparable general health and overall QoL, survivors reported significantly more restrictions on most functioning and symptom scales at each follow-up. Detriments in various QoL dimensions (e.g. physical and social functioning; pain, financial difficulties) aggravated from year 5 to 10. Generally, restrictions were largest for the youngest survivors. CONCLUSION: Relevant restrictions in QoL persist over years in breast cancer survivors and affect predominantly younger women. The aggravation of restrictions in QoL beyond the fifth year may indicate deficits in health care and psychosocial support of breast cancer patients after completion of routine follow-up care.

Using rate advancement periods for communicating the benefits of quitting smoking to older smokers.

BACKGROUND AND AIMS: Standard epidemiological measures of the risk of premature death from smoking might be unsuitable for risk communication in actual counselling situations. The rate advancement period (RAP) is an epidemiologic metric that could be useful for conveying information on the benefits of quitting. More effective risk communication could motivate older smokers to make an attempt at quitting. We provide empirical evidence on the impact of smoking, and the benefits of quitting on all-cause mortality and RAPs for people aged 60 years and older in a large cohort of older adults. METHODS: Smoking information was obtained from 6545 participants aged 60-74 years of ESTHER, a population-based German cohort. Cox proportional hazards regression was applied to estimate associations of smoking status, amount of smoking and time since smoking cessation with all-cause mortality. Premature mortality was quantified by RAPs. RESULTS: Current smokers had a 2.5-fold increased risk for all-cause mortality (adjusted HR: 2.53, 95% CI 2.10 to 3.03) and an RAP of 10.7 years when compared with never smokers. Strong dose-response relationships were seen with both current and life-time amount of smoking. Compared with current smokers, significant mortality reductions by 30%, 39% and 59%, and rate advancement reductions of 4.0, 5.6 and 10.0 years within <10 years, 10-19 years and ≥20 years after cessation were found for former smokers, respectively. CONCLUSIONS: Smoking remains a strong risk factor for premature mortality, and smoking cessation remains highly beneficial also at older ages.

Type 2 diabetes mellitus and gender-specific risk for colorectal neoplasia.

Although a positive association between type 2 diabetes mellitus (T2DM) and colorectal cancer is well established, uncertainty exists about risk differences in diabetic men and women when considering colorectal neoplasia (CN). The main objective was to examine gender-specific associations of T2DM with CN in a population-based cohort study of adults in Germany. This analysis is based on participants of the ESTHER-study, a population-based cohort study. Participants were 50-74 years old at baseline and underwent colonoscopy during 5 year follow-up. CN detected at colonoscopy were validated by medical records review. Total and gender-specific associations of T2DM at baseline and CN were estimated using log-binomial regression. Overall, 55 cases of CN were detected in 166 participants with T2DM and 328 cases in 1,360 participants without T2DM. In women, CN was found in 32 % of participants with T2DM and in 18 % without T2DM (adjusted prevalence ratio (PR): 1.66 95 % CI 1.04-2.64). In men, prevalence for CN was 35 % for those with T2DM and 33 % for those without T2DM (adjusted PR = 1.01; 95 % CI 0.71-1.43). T2DM might have a stronger impact on CN among women than among men. Further research should examine possible reasons for these differences.

Association between the prevalence of depression and age in a large representative German sample of people aged 53 to 80 years.

OBJECTIVE: The aim of the study was to determine the association between the prevalence of clinically significant depression and age in a large representative sample of elderly German people. METHODS: In the second follow-up (2005-2007) of the ESTHER cohort study, the 15-item geriatric depression scale (GDS-15) as well as a sociodemographic and clinical questionnaire were administered to a representative sample of 8270 people of ages 53 to 80 years. The prevalence of clinically significant depression was estimated using a GDS cut-off score of 5/6. Prevalence rates were estimated for the different age categories. Association between depression and age was analyzed using logistic regression, adjusted for gender, co-morbid medical disorders, education, marital status, physical activity, smoking, self-perceived cognitive impairment, and anti-depressive medication. RESULTS: Of the participants, 7878 (95.3%) completed more than twelve GDS items and were included in the study. The prevalence of clinically significant depression was 16.0% (95%CI = [15.2; 16.6]). The function of depression prevalence dependent on age group showed a U-shaped pattern (53-59: 21.0%, CI = [18.9; 23.3]; 60-64: 17.7%, CI = [15.7; 19.7]; 65-69: 12.6%, CI = [11.2; 14.0]; 70-74: 14.4%, CI = [12.6; 16.0]; 75-80: 17.1%, CI = [14.9; 19.4]). Adjusted odds ratios showed that the chances of being depressive decrease with the age category but remain relatively stable for people aged 65 and over. CONCLUSIONS: The prevalence of depression in the elderly seems to be associated with the age category. Adjusted odds ratios showed that people aged 60 and older had lower chances of being depressive than people aged 53 to 59 years.

Low risk of colorectal cancer and advanced adenomas more than 10 years after negative colonoscopy.

BACKGROUND & AIMS: Screening colonoscopy is an effective method to reduce the incidence of and mortality from colorectal cancer (CRC). There is little empirical evidence available about the optimal interval for screening, making this a subject of debate. We associated the prevalence of advanced colorectal neoplasms with time since negative colonoscopies. METHODS: In a study of participants in the German colonoscopy screening program, we determined the prevalence of colorectal neoplasias detected at screening colonoscopy among subjects who had undergone a previous colonoscopy without detection of polyps (negative colonoscopy). Data were compared with that from subjects who had not received colonoscopies. RESULTS: No CRCs were detected in participants who had a previous negative colonoscopy an average of 11.9 years previously (n = 553), compared with the 8.4 CRC cases expected based on age- and gender-specific prevalences among participants who had not received a colonoscopy (n = 2701; standardized prevalence ratio [SPR] = 0.00; 95% confidence interval [CI]: 0.00-0.55). Prevalence of advanced adenoma was also much lower among subjects who had previous colonoscopies (SPR = 0.42; 95% CI: 0.25-0.68). Adjusted prevalence ratios (95% CIs) for detecting an advanced adenoma were 0.38 (95% CI: 0.16-0.90), 0.34 (95% CI: 0.15-0.74), 0.38 (95% CI: 0.16-0.90), and 0.53 (95% CI: 0.27-1.04) among participants with a negative colonoscopy conducted 1-5, 6-10, 11-15, and >16 years ago, respectively, compared to participants with no previous colonoscopy. CONCLUSIONS: The low risk of CRC and advanced adenomas after a negative colonoscopy supports suggestions that screening intervals be extended to > or =10 years.

Male sex and smoking have a larger impact on the prevalence of colorectal neoplasia than family history of colorectal cancer.

BACKGROUND & AIMS: Screening recommendations for colorectal cancer (CRC) commonly take family history but no other risk factors into account. We compared and assessed risk factors of colorectal polyps in a large population undergoing screening colonoscopy. METHODS: We conducted a population-based cross-sectional study that included 3349 subjects, 55 years or older (mean ages of men and women, 63.6 and 63.4 years, respectively), who underwent colonoscopy for the first time within the nationwide colonoscopy screening program in Germany. We calculated prevalences of colorectal polyps and estimated multivariate prevalence ratios (PRs) and population attributable fractions (PAFs). RESULTS: Overall, 654 subjects had hyperplastic polyps (20%), 675 had non-advanced adenomas (20%), 343 had advanced adenomas (10%), and 40 had CRC (1%). Risk factor prevalences and adjusted PRs were higher for male gender and smoking than for family history of CRC. PAFs for prevalence of non-advanced and advanced neoplasia were highest for male gender (23% and 23%, respectively), followed by smoking (7% and 9%, respectively), and family history of CRC (2% and 4%, respectively). CONCLUSIONS: Male gender and smoking have a larger impact on the prevalence of colorectal neoplasia than family history, suggesting an extensive evaluation of additional risk stratification in population-based screening, particularly by sex.

Alcohol consumption and chronic atrophic gastritis: population-based study among 9,444 older adults from Germany.

Moderate alcohol consumption has been suggested to facilitate elimination of Helicobacter pylori infection which is a key risk factor for chronic atrophic gastritis (CAG) and gastric cancer. The aim of our study was to assess the association of alcohol consumption with CAG among older adults from Germany. In the baseline examination of ESTHER, a population-based study conducted in Saarland, serological measurements of pepsinogen I and II (for CAG definition) and H. pylori antibodies were taken in 9,444 subjects aged 50-74 years. Moderate current (<60 g/week) and lifetime (

Association of diabetes and body mass index with levels of prostate-specific antigen: implications for correction of prostate-specific antigen cutoff values?

BACKGROUND: In a recent study, an inverse association between diabetes and prostate-specific antigen (PSA) levels was observed, and several studies reported lower PSA levels in groups with higher body mass index. However, all of the studies were conducted in populations with intensive PSA screening and the role of diabetes severity, duration, and therapy are yet to be explored. METHODS: Associations of diabetes duration and treatment, hemoglobin A1c, and BMI with PSA levels were assessed among 778 men ages 50 to 74 years, randomly chosen from the 2000 to 2002 baseline recruitment of a large population-based cohort study in Germany (prevalence of diabetes, 17%), using linear regression analyses. RESULTS: PSA values were significantly reduced in men with insulin treatment (-39%; P = 0.006) and oral diabetic medication (-24%; P = 0.030), and in men with elevated (6.1-6.9%) and highly (> or =7%) elevated hemoglobin A1c values (-15%, P = 0.004 and -29%, P = 0.003, respectively). PSA reduction was not associated with duration of diabetes. Obesity was possibly associated with a reduction of PSA levels (-14%; P = 0.096). CONCLUSIONS: Our study suggests that more severe forms of diabetes are associated with lower PSA levels and confirms the magnitude of reduction in PSA levels in diabetic men overall. The observed PSA reduction parallels reported risk reduction of prostate cancer among diabetic men.