Genome-wide association studies and Mendelian randomization analyses provide insights into the causes of early-onset colorectal cancer.

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC; diagnosed <50 years of age) is rising globally; however, the causes underlying this trend are largely unknown. CRC has strong genetic and environmental determinants, yet common genetic variants and causal modifiable risk factors underlying EOCRC are unknown. We conducted the first EOCRC-specific genome-wide association study (GWAS) and Mendelian randomization (MR) analyses to explore germline genetic and causal modifiable risk factors associated with EOCRC. PATIENTS AND METHODS: We conducted a GWAS meta-analysis of 6176 EOCRC cases and 65 829 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT), the Colon Cancer Family Registry (CCFR), and the UK Biobank. We then used the EOCRC GWAS to investigate 28 modifiable risk factors using two-sample MR. RESULTS: We found two novel risk loci for EOCRC at 1p34.1 and 4p15.33, which were not previously associated with CRC risk. We identified a deleterious coding variant (rs36053993, G396D) at polyposis-associated DNA repair gene MUTYH (odds ratio 1.80, 95% confidence interval 1.47-2.22) but show that most of the common genetic susceptibility was from noncoding signals enriched in epigenetic markers present in gastrointestinal tract cells. We identified new EOCRC-susceptibility genes, and in addition to pathways such as transforming growth factor (TGF) ß, suppressor of Mothers Against Decapentaplegic (SMAD), bone morphogenetic protein (BMP) and phosphatidylinositol kinase (PI3K) signaling, our study highlights a role for insulin signaling and immune/infection-related pathways in EOCRC. In our MR analyses, we found novel evidence of probable causal associations for higher levels of body size and metabolic factors-such as body fat percentage, waist circumference, waist-to-hip ratio, basal metabolic rate, and fasting insulin-higher alcohol drinking, and lower education attainment with increased EOCRC risk. CONCLUSIONS: Our novel findings indicate inherited susceptibility to EOCRC and suggest modifiable lifestyle and metabolic targets that could also be used to risk-stratify individuals for personalized screening strategies or other interventions.

A pleiotropy scan to discover new susceptibility loci for pancreatic ductal adenocarcinoma.

Pleiotropic variants (i.e., genetic polymorphisms influencing more than one phenotype) are often associated with cancer risk. A scan of pleiotropic variants was successfully conducted ten years ago in relation to pancreatic ductal adenocarcinoma susceptibility. However, in the last decade, genetic association studies performed on several human traits have greatly increased the number of known pleiotropic variants. Based on the hypothesis that variants already associated with a least one trait have a higher probability of association with other traits, 61,052 variants reported to be associated by at least one genome wide association study (GWAS) with at least one human trait were tested in the present study consisting of two phases (discovery and validation), comprising a total of 16,055 pancreatic ductal adenocarcinoma (PDAC) cases and 212,149 controls. The meta-analysis of the two phases showed two loci (10q21.1-rs4948550 (P=6.52×10-5) and 7q36.3-rs288762 (P=3.03×10-5) potentially associated with PDAC risk. 10q21.1-rs4948550 shows a high degree of pleiotropy and it is also associated with colorectal cancer risk while 7q36.3-rs288762 is situated 28,558 base pairs upstream of the Sonic Hedgehog (SHH) gene, which is involved in the cell differentiation process and PDAC etiopathogenesis. In conclusion, none of the single nucleotide polymorphisms (SNPs) showed a formally statistically significant association after correction for multiple testing. However, given their pleiotropic nature and association with various human traits including colorectal cancer, the two SNPs showing the best associations with PDAC risk merit further investigation through fine mapping and ad hoc functional studies.

Prediction of clinical diagnosis of Alzheimer's disease, vascular, mixed, and all-cause dementia by a polygenic risk score and APOE status in a community-based cohort prospectively followed over 17 years.

The strongest genetic risk factor for Alzheimer's disease (AD) is the ε4 allele of Apolipoprotein E (APOE) and recent genome-wide association meta-analyses have confirmed additional associated genetic loci with smaller effects. The aim of this study was to investigate the ability of an AD polygenic risk score (PRS) and APOE status to predict clinical diagnosis of AD, vascular (VD), mixed (MD), and all-cause dementia in a community-based cohort prospectively followed over 17 years and secondarily across age, sex, and education strata. A PRS encompassing genetic variants reaching genome-wide significant associations to AD (excluding APOE) from the most recent genome-wide association meta-analysis data was calculated and APOE status was determined in 5203 participants. During follow-up, 103, 111, 58, and 359 participants were diagnosed with AD, VD, MD, and all-cause dementia, respectively. Prediction ability of AD, VD, MD, and all-cause dementia by the PRS and APOE was assessed by multiple logistic regression and receiver operating characteristic curve analyses. The PRS per standard deviation increase in score and APOE4 positivity (≥1 ε4 allele) were significantly associated with greater odds of AD (OR, 95% CI: PRS: 1.70, 1.45-1.99; APOE4: 3.34, 2.24-4.99) and AD prediction accuracy was significantly improved when adding the PRS to a base model of age, sex, and education (ASE) (c-statistics: ASE, 0.772; ASE + PRS, 0.810). The PRS enriched the ability of APOE to discern AD with stronger associations than to VD, MD, or all-cause dementia in a prospective community-based cohort.

Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma.

Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values <0.05 considered significant. K3326X and I157T were associated with increased risk of developing sporadic PDAC (odds ratio (ORdom ) = 1.78, 95% confidence interval (CI) = 1.26-2.52, p = 1.19 × 10-3 and ORdom = 1.74, 95% CI = 1.15-2.63, p = 8.57 × 10-3 , respectively). Neither mutation was significantly associated with risk of developing early-onset PDAC. This retrospective study demonstrates novel risk estimates of K3326X and I157T in sporadic PDAC which suggest that upon validation and in combination with other established genetic and non-genetic risk factors, these mutations may be used to improve pancreatic cancer risk assessment in European populations. Identification of carriers of these risk alleles as high-risk groups may also facilitate screening or prevention strategies for such individuals, regardless of family history.

Meeting report from the joint IARC-NCI international cancer seminar series: a focus on colorectal cancer.

Despite significant progress in our understanding of the etiology, biology and genetics of colorectal cancer, as well as important clinical advances, it remains the third most frequently diagnosed cancer worldwide and is the second leading cause of cancer death. Based on demographic projections, the global burden of colorectal cancer would be expected to rise by 72% from 1.8 million new cases in 2018 to over 3 million in 2040 with substantial increases anticipated in low- and middle-income countries. In this meeting report, we summarize the content of a joint workshop led by the National Cancer Institute and the International Agency for Research on Cancer, which was held to summarize the important achievements that have been made in our understanding of colorectal cancer etiology, genetics, early detection and treatment and to identify key research questions that remain to be addressed.

Screening for gastric cancer using exhaled breath samples.

BACKGROUND: The aim was to derive a breath-based classifier for gastric cancer using a nanomaterial-based sensor array, and to validate it in a large screening population. METHODS: A new training algorithm for the diagnosis of gastric cancer was derived from previous breath samples from patients with gastric cancer and healthy controls in a clinical setting, and validated in a blinded manner in a screening population. RESULTS: The training algorithm was derived using breath samples from 99 patients with gastric cancer and 342 healthy controls, and validated in a population of 726 people. The calculated training set algorithm had 82 per cent sensitivity, 78 per cent specificity and 79 per cent accuracy. The algorithm correctly classified all three patients with gastric cancer and 570 of the 723 cancer-free controls in the screening population, yielding 100 per cent sensitivity, 79 per cent specificity and 79 per cent accuracy. Further analyses of lifestyle and confounding factors were not associated with the classifier. CONCLUSION: This first validation of a nanomaterial sensor array-based algorithm for gastric cancer detection from breath samples in a large screening population supports the potential of this technology for the early detection of gastric cancer.

Incident depression and mortality among people with different types of dementia: results from a longitudinal cohort study.

PURPOSE: The aim of this study was to investigate the independent and combined association of incident depression and dementia with mortality and to explore whether the magnitude of the association varies according to different types of dementia, including Alzheimer's disease and vascular dementia. METHODS AND DESIGN: The study was based on a population-based longitudinal cohort consisting of 9940 participants at baseline and followed for over 14 years. The sample used for the analyses included 6114 participants with available information on diagnosis of incident dementia and depression. For survival analyses, Cox regression models with incident dementia (n = 293; 5%) and incident depression (n = 746; 12%) as time-dependent variables were used. RESULTS: Cox models adjusted for relevant confounders indicated that comorbidity of incident vascular dementia and incident depression was associated with a much higher mortality risk (HR 6.99; 95% CI 3.84-12.75) than vascular dementia in the absence of depression (HR 2.80; 95% CI 1.92-4.08). In contrast, estimates for comorbidity of Alzheimer's disease and depression were slightly lower than those for Alzheimer in absence of depression (HR 3.56; 95% CI 1.83-6.92 and HR 4.19; 95% CI 2.97-5.90, respectively). Incident depression in the absence of incident dementia was only weakly associated with mortality. CONCLUSIONS: These findings indicate that depression and vascular dementia might have synergistic effects on mortality. The results have relevant public health implications for prevention, routine screening for and early treatment of depression among older people, especially those at risk of vascular dementia.

Lifestyle factors and risk of sporadic colorectal cancer by microsatellite instability status: a systematic review and meta-analyses.

Introduction: The association of lifestyle factors with molecular pathological subtypes of colorectal cancer (CRC), such as microsatellite instability (MSI), could provide further knowledge about the colorectal carcinogenic process. The aim of this review was to evaluate possible associations between lifestyle factors and risk of sporadic CRC by MSI status. Methods: PubMed and Web of Science were searched for studies investigating the association between alcohol, body mass index, dietary fiber, hormone replacement therapy (HRT), non-steroidal anti-inflammatory drugs, physical activity, red meat, smoking, or statin use, with MSI-high (MSI-H) and microsatellite stable (MSS) CRC. Meta-analyses were carried out to calculate summary relative risks (sRR). Results: Overall, 31 studies reporting on the association between lifestyle factors and CRC according to MSI status were included in this review. Ever smoking was associated with MSI-H (sRR = 1.62; 95% CI: 1.40-1.88) and MSS/MSI-low CRC (sRR = 1.10; 95% CI: 1.01-1.20), but the association was significantly stronger for MSI-H CRC. The use of HRT was associated with a 20% decrease (sRR = 0.80; 95% CI: 0.73-0.89) in the risk of MSS CRC, but was not associated with MSI-H CRC. An increase in body mass index per 5 kg/m2 was equally associated with MSS and MSI-H CRC (sRR = 1.22, in both cases), but was statistically significant for MSS CRC only (95% CI: 1.11-1.34 and 0.94-1.58, respectively). Limited evidence for associations between other lifestyle factors and CRC by MSI status exists. Conclusions: Lifestyle factors, such as HRT and smoking are differentially associated with the risk of MSI-H and MSS CRC. Further research on associations of lifestyle factors and CRC subtypes is necessary to provide a better understanding of the CRC disease pathway.

Impact of prediagnostic smoking and smoking cessation on colorectal cancer prognosis: a meta-analysis of individual patient data from cohorts within the CHANCES consortium.

Background: Smoking has been associated with colorectal cancer (CRC) incidence and mortality in previous studies and might also be associated with prognosis after CRC diagnosis. However, current evidence on smoking in association with CRC prognosis is limited. Patients and methods: For this individual patient data meta-analysis, sociodemographic and smoking behavior information of 12 414 incident CRC patients (median age at diagnosis: 64.3 years), recruited within 14 prospective cohort studies among previously cancer-free adults, was collected at baseline and harmonized across studies. Vital status and causes of death were collected for a mean follow-up time of 5.1 years following cancer diagnosis. Associations of smoking behavior with overall and CRC-specific survival were evaluated using Cox regression and standard meta-analysis methodology. Results: A total of 5229 participants died, 3194 from CRC. Cox regression revealed significant associations between former [hazard ratio (HR) = 1.12; 95 % confidence interval (CI) = 1.04-1.20] and current smoking (HR = 1.29; 95% CI = 1.04-1.60) and poorer overall survival compared with never smoking. Compared with current smoking, smoking cessation was associated with improved overall (HR<10 years = 0.78; 95% CI = 0.69-0.88; HR≥10 years = 0.78; 95% CI = 0.63-0.97) and CRC-specific survival (HR≥10 years = 0.76; 95% CI = 0.67-0.85). Conclusion: In this large meta-analysis including primary data of incident CRC patients from 14 prospective cohort studies on the association between smoking and CRC prognosis, former and current smoking were associated with poorer CRC prognosis compared with never smoking. Smoking cessation was associated with improved survival when compared with current smokers. Future studies should further quantify the benefits of nonsmoking, both for cancer prevention and for improving survival among CRC patients, in particular also in terms of treatment response.

[Morbidity Differences by Health Insurance Status in Old Age]. / Unterschiede in der Morbidität nach Krankenversichertenstatus im Alter.

BACKGROUND: Morbidity differences between older members of private and statutory health insurance Germany have rarely been examined. Thus, we aimed at determining these differences in old age. METHODS: This study used data from 2 follow-up waves with a 3-year interval from a population-based prospective cohort study (ESTHER study) in Saarland, Germany. Morbidity was assessed by participants' GPs using a generic instrument (Cumulative Illness Rating Scale for Geriatrics). The between estimator was used which exclusively quantifies inter-individual variation. Adjusting for sex and age, we investigated the association between health insurance and morbidity in the main model. In additional models, we adjusted incrementally for the effect of education, family status and income. RESULTS: Regression models not adjusting for income showed that members of private health insurance had a lower morbidity score than members of statutory health insurance. This effect is considerably lower in models adjusting for income, but remained statistically significant (except for men). CONCLUSION: Observed differences in morbidity between older members of private and statutory health insurance can partly be explained by income differences. Thus, our findings highlight the role of model specification in determining the relation between morbidity and health insurance.

Excess mortality after hip fracture in elderly persons from Europe and the USA: the CHANCES project.

BACKGROUND: Hip fractures are associated with diminished quality of life and survival especially amongst the elderly. OBJECTIVE: All-cause mortality after hip fracture was investigated to assess its magnitude. METHODS: A total of 122 808 participants from eight cohorts in Europe and the USA were followed up for a mean of 12.6 years, accumulating 4273 incident hip fractures and 27 999 deaths. Incident hip fractures were assessed through telephone interviews/questionnaires or national inpatient/fracture registries, and causes of death were verified with death certificates. Cox proportional hazards models and the time-dependent variable methodology were used to assess the association between hip fracture and mortality and its magnitude at different time intervals after the injury in each cohort. We obtained the effect estimates through a random-effects meta-analysis. RESULTS: Hip fracture was positively associated with increased all-cause mortality; the hazard ratio (HR) in the fully adjusted model was 2.12, 95% confidence interval (CI) 1.76-2.57, after adjusting for potential confounders. This association was stronger amongst men [HR: 2.39, 95% CI: 1.72-3.31] than amongst women [HR: 1.92, 95% CI: 1.54-2.39], although this difference was not significant. Mortality was higher during the first year after the hip fracture [HR: 2.78, 95% CI: 2.12-3.64], but it remained elevated without major fluctuations after longer time since hip fracture [HR (95% CI): 1.89 (1.50-2.37) after 1-4 years; 2.15 (1.81-2.55) after 4-8 years; 1.79 (1.57-2.05) after 8 or more years]. CONCLUSION: In this large population-based sample of older persons across eight cohorts, hip fracture was associated with excess short- and long-term all-cause mortality in both sexes.

New approach shows no association between maternal milk fatty acid composition and childhood wheeze or asthma.

BACKGROUND: Previous observational studies have implied breastmilk fatty acid composition may play a role in the development of atopic eczema or atopic sensitization in breastfed infants and toddlers. However, studies investigating associations with wheeze and asthma in later childhood are scarce and did not account for inherent correlation of compositional data. Our aim was to explore the association of maternal milk fatty acid composition with childhood wheezing phenotypes and asthma up to age 13 years using a new statistical approach. METHODS: Breastmilk was collected 6 weeks and 6 months postdelivery in the Ulm Birth Cohort Study (n=720 and n=454, respectively). Concentrations of 28 fatty acids were measured by high-resolution capillary gas-liquid chromatography. To control for constant-sum constraint, concentration data were transformed using the centered log ratio method. Compositional biplots and correlation matrices were used to group centered log ratio transformed fatty acids. Adjusted risk ratios with parent-reported wheezing phenotypes and doctor-diagnosed asthma were computed using a modified Poisson regression. RESULTS: We observed no straightforward evidence of associations between overall breastmilk fatty acid composition and specific wheeze phenotypes or doctor-diagnosed asthma. CONCLUSION: Using appropriate statistical methodology, we report null associations. These findings may partly be attributable to several cohort-specific factors associated with breastfeeding and breastmilk collection. Further studies could improve on ours by analyzing samples of breastmilk and formula and by including all children for whom these are exclusively or together the major source of fatty acids in the first months of life.

[Which Factors Affect Out-of-pocket Payments for Health Care Services Among Elderly Germans? Results of a Longitudinal Study]. / Welche Faktoren beeinflussen die privaten Zuzahlungen zu Gesundheitsleistungen im Alter? Ergebnisse einer Längsschnittstudie.

Background: In Germany, out-of-pocket payments (OOPP) account for a large proportion of total health expenditure. However, there are only few investigations on how morbidity-related, sociodemographic and lifestyle factors affect OOPP particularly in the older population. The aim of this study was to identify factors affecting OOPP for health care services among elderly Germans in a longitudinal setting. Methods: This longitudinal study used data from 2 follow-up waves (3-year interval) from a population-based prospective cohort study (ESTHER study) collected in Saarland, Germany. At the first follow-up wave, subjects were between 57 and 84 years old. Participants provided comprehensive data including individual OOPP for the preceding 3 months. Fixed effects (FE) regressions were used to determine factors affecting OOPP. Results: Mean individual OOPP (3-month period) rose from € 119 (first wave) to € 136 (second wave). Longitudinal regressions showed that higher morbidity did not affect OOPP. Moreover, changes in sociodemographic as well as lifestyle factors were not related to changes in OOPP. Solely, exemption of OOPP reduced the dependent variable significantly. Conclusion: In contrast to cross-sectional findings for Germany, OOPP are not related to morbidity and income in this study. This underlines the complex nature of OOPP in old age and the need for longitudinal studies to gain some insight into the underlying causal factors.

HbA1c levels in non-diabetic older adults - No J-shaped associations with primary cardiovascular events, cardiovascular and all-cause mortality after adjustment for confounders in a meta-analysis of individual participant data from six cohort studies.

BACKGROUND: To determine the shape of the associations of HbA1c with mortality and cardiovascular outcomes in non-diabetic individuals and explore potential explanations. METHODS: The associations of HbA1c with all-cause mortality, cardiovascular mortality and primary cardiovascular events (myocardial infarction or stroke) were assessed in non-diabetic subjects ≥50 years from six population-based cohort studies from Europe and the USA and meta-analyzed. Very low, low, intermediate and increased HbA1c were defined as <5.0, 5.0 to <5.5, 5.5 to <6.0 and 6.0 to <6.5% (equals <31, 31 to <37, 37 to <42 and 42 to <48 mmol/mol), respectively, and low HbA1c was used as reference in Cox proportional hazards models. RESULTS: Overall, 6,769 of 28,681 study participants died during a mean follow-up of 10.7 years, of whom 2,648 died of cardiovascular disease. Furthermore, 2,493 experienced a primary cardiovascular event. A linear association with primary cardiovascular events was observed. Adjustment for cardiovascular risk factors explained about 50% of the excess risk and attenuated hazard ratios (95 confidence interval) for increased HbA1c to 1.14 (1.03-1.27), 1.17 (1.00-1.37) and 1.19 (1.04-1.37) for all-cause mortality, cardiovascular mortality and cardiovascular events, respectively. The six cohorts yielded inconsistent results for the association of very low HbA1c levels with the mortality outcomes and the pooled effect estimates were not statistically significant. In one cohort with a pronounced J-shaped association of HbA1c levels with all-cause and cardiovascular mortality (NHANES), the following confounders of the association of very low HbA1c levels with mortality outcomes were identified: race/ethnicity; alcohol consumption; BMI; as well as biomarkers of iron deficiency anemia and liver function. Associations for very low HbA1c levels lost statistical significance in this cohort after adjusting for these confounders. CONCLUSIONS: A linear association of HbA1c levels with primary cardiovascular events was observed. For cardiovascular and all-cause mortality, the observed small effect sizes at both the lower and upper end of HbA1c distribution do not support the notion of a J-shaped association of HbA1c levels because a certain degree of residual confounding needs to be considered in the interpretation of the results.

Survival with nonmelanoma skin cancer in Germany.

BACKGROUND: Nonmelanoma skin cancer (NMSC) is the most common cancer in Germany, but detailed information on survival is lacking. OBJECTIVES: To provide survival estimates for female and male patients with basal cell carcinoma (BCC), squamous cell carcinoma (SCC), sarcoma, adenocarcinoma and Merkel cell carcinoma. Further subgroup analyses were carried out by age, tumour stage and body site. METHODS: In total 459 640 patients diagnosed with NMSC in 1997-2011 were included from population-based cancer registers, covering a population of 33 million inhabitants. Age-standardized absolute and relative 5-year and 10-year survival were calculated using period analysis. RESULTS: The absolute and relative 5-year survival were 87·1% and 102·9% for BCC, 77·6% and 93·6% for SCC, 82·1% and 96·0% for sarcoma, 71·4% and 85·7% for adenocarcinoma and 60·0% and 70·7% for Merkel cell carcinoma, respectively. Higher age, female sex and advanced stage were associated with lower survival. CONCLUSIONS: A comprehensive overview of NMSC survival in Germany is provided. The differences between the NMSC subtypes require a more differentiated consideration of patient survival. The survival advantage of patients with BCC may be related to health-promoting factors related to the BCC diagnosis, such as changes to a healthier lifestyle.

[Diverging detection limits of immunochemical tests for occult blood underline the necessity of standardization and quality assurance]. / Unterschiedliche Nachweisgrenzen immunologischer Tests auf Blut im Stuhl unterstreichen die Notwendigkeit der Standardisierung und Qualitätssicherung.

BACKGROUND: Immunological fecal occult blood tests (FIT) are superior in detecting colorectal cancer and its precursors compared to conventional Guajac-based tests. Besides quantitative, laboratory-based FITs qualitative, office-based FITs are increasingly employed. Studies have shown major variation of these tests with respect to sensitivity and specificity, which is most probably caused by different detection limits. In the present study we therefore determined and compared the detection limits and other criteria of commercial FITs. METHODS: We determined the detection limits for 21 qualitative and one quantitative FIT using commercial control solutions with defined hemoglobin (Hb) concentrations. These detection limits were compared with the manufacturers' data. RESULTS: The detection limits of the tests showed a wide range of 2 to over 60 µg Hb per gram stool. In many cases the detection limits we determined were not in accordance with the manufacturers' data. Two tests didn't show a positive reaction even with the highest hemoglobin concentration of 440 ng/mL. On the other hand one test showed a positive reaction even at the lowest hemoglobin concentration of 25 ng/mL. CONCLUSION: The large differences in the detection limits found in this study are consistent with observations of large variation of sensitivity and specificity of qualitative FITs in screening practice. Proper clinical validation of each FIT is to be required before admission for colorectal cancer screening. An additional regular quality control, i. e. by means of external quality control measures and documentation of results of colonoscopies following positive tests results, should be mandatory.

[Treatment preferences of elderly patients with mental disorders]. / Behandlungswünsche von älteren Menschen mit psychischen Erkrankungen.

BACKGROUND: Successful treatment in psychosomatic medicine requires intrinsic motivation of the patient and the belief that the chosen therapeutic option can help. Depression, somatization disorder and generalized anxiety disorder (GAD) are frequent mental disorders in the elderly population. Finding a suitable and successful treatment for elderly people with mental disorders is often difficult. Undertreatment and the utilization of inappropriate healthcare services are frequent. OBJECTIVE: Treatment preferences of elderly patients with mental disorders were ascertained in order to evaluate the motivation for psychotherapy or other therapeutic measures. MATERIAL AND METHODS: The data were derived from the 8-year follow-up of the epidemiological study on chances of prevention, early recognition and optimized therapy of chronic diseases in the elderly population (ESTHER), a population-based cohort study in Saarland, Germany. A total of 3124 patients aged 55-84 years were included in this analysis. The treatment preferences were documented using a questionnaire with 12 different answer categories. The occurrence of depression, somatization disorder and GAD was collated using the patient health questionnaire (PHQ-D). RESULTS: Physiotherapy and inpatient rehabilitation were the most frequently named treatment preferences in all three subgroups of patients with mental disorders. Psychotherapy was the preferred treatment for 18.3 % of depressive patients, for 15.0 % of somatization patients and for 15.7 % of GAD patients. CONCLUSION: Mentally ill elderly patients in Germany preferred physical treatment techniques, such as physiotherapy and inpatient rehabilitation over psychotherapy. Discussion is needed over the reasons for these findings and the clinical implications.

Genetic variants in DNA repair genes as potential predictive markers for oxaliplatin chemotherapy in colorectal cancer.

Oxaliplatin-based chemotherapy exerts its effects through generating DNA damage. Hence, genetic variants in DNA repair pathways could modulate treatment response. We used a prospective cohort of 623 colorectal cancer patients with stage II-IV disease treated with adjuvant/palliative chemotherapy to comprehensively investigate 1727 genetic variants in the DNA repair pathways as potential predictive markers for oxaliplatin treatment. Single nucleotide polymorphisms (SNP) associations with overall survival and recurrence-free survival were assessed using a Cox regression model. Pathway analysis was performed using the gamma method. Patients carrying variant alleles of rs3783819 (MNAT1) and rs1043953 (XPC) experienced a longer overall survival after treatment with oxaliplatin than patients who did not carry the variant allele, while the opposite association was found in patients who were not treated with oxaliplatin (false discovery rate-adjusted P-values for heterogeneity 0.0047 and 0.0237, respectively). The nucleotide excision repair (NER) pathway was found to be most likely associated with overall survival in patients who received oxaliplatin (P-value=0.002). Our data show that genetic variants in the NER pathway are potentially predictive of treatment response to oxaliplatin.