Display omitted
Demographic aging is expected to increase the number of colorectal cancer (CRC) cases in many countries. Screening for CRC can substantially reduce the disease burden but its use has ...remained rather limited in Germany. We aimed to quantify the expected impact of demographic aging on the future CRC burden and the potential to reduce that burden by increased use of screening colonoscopy offers in Germany.
We obtained sex- and age-specific data on colonoscopy use from AOK, the biggest health insurance provider in Germany, and combined these with the projected demographic development and current CRC incidence rates. We estimated the number of new CRC cases until 2060, assuming screening colonoscopy use to be constant or to increase to between 1·5 and 3 times the current levels.
Ten-year screening colonoscopy utilization rates were low (<20% in both sexes in all age groups). Assuming no change in screening colonoscopy use, the overall annual caseload was predicted to increase from approximately 62,000 cases in 2020 to more than 70,000 cases by the year 2040 and more than 75,000 cases by 2050. To avoid increasing case numbers, an increase of screening colonoscopy use to more than 3 times current levels would be needed.
At current levels of screening use, the strong effects of the demographic aging imply that the CRC caseload will significantly increase in the decades to come. CRC screening efforts will need to be substantially increased to even maintain the current level of incident cases.
German Federal Ministry of Education and Research (grant 01GL1712).
A sizable fraction of colorectal cancer (CRC) is expected to be explained by heritable factors, with heritability estimates ranging from 12 to 35% twin and family studies. Genome-wide association ...studies (GWAS) have successfully identified a number of common single-nucleotide polymorphisms (SNPs) associated with CRC risk. Although it has been shown that these CRC susceptibility SNPs only explain a small proportion of the genetic risk, it is not clear how much of the heritability these SNPs explain and how much is left to be detected by other, yet to be identified, common SNPs. Therefore, we estimated the heritability of CRC under different scenarios using Genome-Wide Complex Trait Analysis in the Genetics and Epidemiology of Colorectal Cancer Consortium including 8025 cases and 10 814 controls. We estimated that the heritability explained by known common CRC SNPs identified in GWAS was 0.65% (95% CI:0.3-1%; P = 1.11 × 10-16), whereas the heritability explained by all common SNPs was at least 7.42% (95% CI: 4.71-10.12%; P = 8.13 × 10(-8)), suggesting that many common variants associated with CRC risk remain to be detected. Comparing the heritability explained by the common variants with that from twin and family studies, a fraction of the heritability may be explained by other genetic variants, such as rare variants. In addition, our analysis showed that the gene × smoking interaction explained a significant proportion of the CRC variance (P = 1.26 × 10(-2)). In summary, our results suggest that known CRC SNPs only explain a small proportion of the heritability and more common SNPs have yet to be identified.
Despite consistent evidence that comorbidities and functional status (FS) are strong prognostic factors for colorectal cancer (CRC) patients, these important characteristics are not considered in ...prognostic nomograms. We assessed to what extent incorporating these characteristics into prognostic models enhances prediction of CRC prognosis. CRC patients diagnosed in 2003–2014 who were recruited into a population-based study in Germany and followed over a median time of 4.7 years were randomized into training (n = 1608) and validation sets (n = 1071). In the training set, Cox models with predefined variables (age, sex, stage, tumor location, comorbidity scores, and FS) were used to construct nomograms for relevant survival outcomes. The performance of the nomograms, compared to models without comorbidity and FS, was evaluated in the validation set using concordance index (C-index). The C-indexes of the nomograms for overall and disease-free survival in the validation set were 0.768 and 0.737, which were substantially higher than those of models including tumor stage only (0.707 and 0.701) or models including stage, age, sex, and tumor location (0.749 and 0.718). The nomograms enabled significant risk stratification within all stages including stage IV. Our study suggests that incorporating comorbidities and FS into prognostic nomograms could substantially enhance prediction of CRC prognosis.
Introduction
Whether and to what extent the relationship between physical activity (PA) and colorectal cancer (CRC) differs according to CRC‐related genetic risk remains to be determined, and no ...studies to date have quantified how much genetically determined risk could be compensated for with active exercise.
Methods
Genetic risk was quantified by a polygenic risk score (PRS) summarizing the estimated effect of 140 CRC‐associated genetic variants. Associations of PA with CRC risk were estimated by multivariable logistic regression across PRS levels. We also compared the impact of PA and specific PA types to the PRS using “genetic risk equivalent (GRE)”, a novel approach to enhance effective risk communication.
Results
Among 5058 CRC patients and 4134 controls, we observed no significant association between overall PA level in quartiles and CRC risk. However, the highest versus lowest lifetime leisure time physical activity (LTPA) was associated with a 13% lower CRC risk odds ratio 0.87, 95% confidence interval (CI) 0.77–1.00 independent of PRS levels (adjusted p value for interaction = 0.18). This effect was equivalent to the effect of having 11 percentiles lower PRS (GRE −10.6, 95% CI −20.7 to −0.6). The GRE (95% CI) for the highest lifetime sports tertile was −23.0 (−33.9 to −12.0).
Conclusions
LTPA was inversely associated with CRC risk irrespective of polygenic risk for CRC, which reinforces the importance of LTPA in CRC prevention among the general population. Adequate sports activity can compensate for a large share of polygenic risk for CRC.
This study, based on a large ongoing case‐control study (the DACHS study) on CRC in Germany, adds to the limited evidence of the individual and joint association of PA and polygenic risk score (PRS) with CRC risk and compares these associations using a novel metric of GRE for effective risk communication. We found that leisure time PA, in particular sports, was associated with reduced CRC risk regardless of PRS levels. The high GREs suggest that adequate sports activity can compensate for a large share of predetermined polygenic risk for CRC.
Background The incidence of adverse events (AEs) is a crucial factor when colonoscopy is considered for mass screening, but few studies have addressed delayed and non-GI AEs. Objectives To ...investigate the risk of AEs requiring hospitalization after screening and nonscreening colonoscopies compared with control subjects who did not undergo colonoscopy. Design Retrospective matched cohort. Setting Statutory health insurance fund in Germany. Patients A total of 33,086 individuals who underwent colonoscopy as an outpatient (8658 screening, 24,428 nonscreening) and 33,086 matched controls who did not undergo colonoscopy. Interventions Outpatient screening and nonscreening colonoscopies. Main Outcomes Measurements Risk of AEs (perforation, bleeding, myocardial infarction, stroke, splenic injury, and others) requiring hospitalization within 30 days after colonoscopy/index date and risk differences between the group that underwent colonoscopy and the group that did not. Results The incidence of perforation was 0.8 (95% confidence interval CI, 0.3-1.7) and 0.7 (95% CI, 0.4-1.1) per 1000 screening and nonscreening colonoscopies, respectively. Hospitalizations because of bleeding occurred in 0.5 (95% CI, 0.1-1.2) and 1.1 (95% CI, 0.8-1.7) per 1000 screening and nonscreening colonoscopies, respectively. The incidence of myocardial infarction, stroke, and other non-GI AEs was similar in colonoscopy and control groups. No splenic injury was observed. Those with AEs generally had a higher mean age and comorbidity rate than the overall study population. Limitations The analysis relies on health insurance claims data. Conclusions This study provides further evidence of the safety of colonoscopy in routine practice with regard to delayed and non-GI AEs. Hospitalizations because of the investigated AEs were uncommon or rare for both screening and nonscreening colonoscopies.
PDF
