Background & Aims Data from randomized controlled trials on the effects of screening colonoscopies on colorectal cancer (CRC) incidence and mortality are not available. Observational studies have ...suggested that colonoscopies strongly reduce the risk of CRC, but there is little specific evidence on the effects of screening colonoscopies. Methods We performed a population-based case-control study of 3148 patients with a first diagnosis of CRC (cases) and 3274 subjects without CRC (controls) from the Rhine-Neckar region of Germany from 2003 to 2010. Detailed information on previous colonoscopy and potential confounding factors was collected by standardized personal interviews. Self-reported information on colonoscopies and their indications was validated by medical records. We used multiple logistic regression to assess the association between colonoscopy conducted for specific indications within the past 10 years and risk of CRC. Results A history of colonoscopy was associated with a reduced subsequent risk of CRC, independently of the indication for the examination. However, somewhat stronger associations were found for examinations with screening indications (adjusted odds ratio OR 0.09, 95% confidence interval CI 0.07–0.13) than for examinations with diagnostic indications, such as positive fecal occult blood test result (OR, 0.33; 95% CI, 0.19–0.57), surveillance after a preceding colonoscopy (OR, 0.33; 95% CI, 0.24–0.45), rectal bleeding (OR, 0.28; 95% CI, 0.20–0.40), abdominal symptoms (OR, 0.15; 95% CI, 0.10–0.21), or other (OR, 0.21; 95% CI, 0.14–0.30). Colonoscopy was also associated with a reduced risk of cancer in the right colon, regardless of the indication, although to a smaller extent than for other areas of the colon (OR for screening colonoscopy, 0.22; 95% CI, 0.14–0.33). Conclusions In a population-based case-control study, the risk of CRC was strongly reduced up to 10 years after colonoscopy for any indication. Risk was particularly low after screening colonoscopy, even for cancer in the right colon.
Summary
Background
The regular use of non‐steroidal anti‐inflammatory drugs (NSAIDs) has been associated with reduced colorectal cancer (CRC) risk.
Aim
To explore whether this association varies ...according to background polygenic risk for CRC.
Methods
Data were collected from a large population‐based case‐control study on CRC in Germany. A polygenic risk score (PRS) based on 140 CRC‐related risk loci was used to quantify the genetic risk. The associations of regular use of NSAIDs (≥2times per week for at least 1 year) with CRC risk were estimated in the whole population and in subgroups according to PRS levels using multivariable logistic regression. The impact of NSAIDs on CRC risk was compared to PRS using the ‘genetic risk equivalent’ (GRE), a recently developed metric for effective risk communication.
Results
In total 5129 CRC cases and 4093 controls were included in this analysis. The regular use of NSAIDs (including aspirin) was associated with reduced CRC risk odds ratio (OR) 0.66, 95% confidence interval (CI) 0.59, 0.74, as was regular use of aspirin only (OR 0.73, 95% CI 0.65, 0.83), without indication of interaction with the PRS (P = 0.10 and 0.22 respectively). The effect of NSAID use was equivalent to the effect of having a 32 percentiles lower PRS (GRE −32, 95% CI −41, −22).
Conclusions
The regular use of NSAIDs is associated with greatly reduced CRC risk regardless of individual genetic profile. With an equivalent reduction of relative risk across all polygenic risk groups, absolute risk reduction would be expected to be strongest among those with the highest polygenic risk score.
The regular use of NSAIDs is associated with greatly reduced colorectal cancer (CRC) risk regardless of polygenic risk for CRC. The estimated large genetic risk equivalent indicates that a substantial proportion of genetic risk could be compensated for with regular use of NSAIDs.
Circulating microRNAs (miRNAs) have been proposed as minimally invasive prognostic markers for various types of cancers, including colorectal cancer (CRC), the third most diagnosed cancer worldwide. ...We aimed to evaluate the levels of circulating miRNAs that might serve as markers for CRC prognosis and survival. We included plasma samples of 543 CRC patients with stage I‐IV disease from a population‐based study carried out in Germany. After comprehensive evaluation of current literature, 95 miRNAs were selected and measured with Custom TaqMan® Array MicroRNA Cards. Plasma samples of non‐metastatic and metastatic colon cancer patients, each group consisting of ten patients with ‘good’ and ten patients with ‘bad’ prognosis were screened. Identified candidate miRNAs were further validated by RT‐qPCR in the whole study cohort. The association of the miRNA levels with patients' survival and the prognostic subtypes was analyzed with uni‐ and multivariate logistic regression and Cox proportional hazards regression models. Increased miR‐122 levels were associated with a ‘bad’ prognostic subtype in metastatic CRC (Odds ratio: 1.563, 95% confidence interval (CI): 1.038‐2.347) and a shorter relapse‐free survival and overall survival for non‐metastatic (Hazard ratio (HR): 1.370, 95% CI: 1.028‐1.825; HR: 1.353, 95% CI: 1.002‐1.828) and metastatic (HR: 1.264, 95% CI: 1.050‐1.520; HR: 1.292, 95% CI: 1.078‐1.548) CRC patients. Additionally, several members of the miR‐200 family showed associations with patients' prognosis and correlations to clinicopathological characteristics. The here identified miRNA markers, miR‐122 and the miR‐200 family members, could be of use in the development of a multi‐marker blood test for CRC prognosis.
What's new?
Metastasis is the major cause of death for colorectal cancer (CRC) patients. Prognostic markers that are constantly measurable using liquid biopsies could facilitate the earlier prediction of relapse events and metastasis formation. In a prospective study cohort of 543 colorectal cancer patients, the authors evaluated the role of circulating miRNAs as potential prognostic markers for CRC with a specific focus on miRNAs known to be involved in tumor progression and metastasis formation. MiR‐122 and several members of the miR‐200 family were identified as prognostic markers, suggesting their potential use in the development of a multi‐marker blood test for CRC prognosis.
Cancer‐related fatigue is a frequent, burdensome and often insufficiently treated symptom. A more targeted treatment of fatigue is urgently needed. Therefore, we examined biomarkers and clinical ...factors to identify fatigue subtypes with potentially different pathophysiologies. The study population comprised disease‐free breast cancer survivors of a German population‐based case‐control study who were re‐assessed on average 6 (FU1, n = 1871) and 11 years (FU2, n = 1295) after diagnosis. At FU1 and FU2, we assessed fatigue with the 20‐item multidimensional Fatigue Assessment Questionnaire and further factors by structured telephone‐interviews. Serum samples collected at FU1 were analyzed for IL‐1ß, IL‐2, IL‐4, IL‐6, IL‐10, TNF‐a, GM‐CSF, IL‐5, VEGF‐A, SAA, CRP, VCAM‐1, ICAM‐1, leptin, adiponectin and resistin. Exploratory cluster analyses among survivors with fatigue at FU1 and no history of depression yielded three clusters (CL1, CL2 and CL3). CL1 (n = 195) on average had high levels of TNF‐α, IL1‐β, IL‐6, resistin, VEGF‐A and GM‐CSF, and showed high BMI and pain levels. Fatigue in CL1 manifested rather in physical dimensions. Contrarily, CL2 (n = 78) was characterized by high leptin level and had highest cognitive fatigue. CL3 (n = 318) did not show any prominent characteristics. Fatigued survivors with a history of depression (n = 214) had significantly higher physical, emotional and cognitive fatigue and showed significantly less amelioration of fatigue from FU1 to FU2 than survivors without depression. In conclusion, from the broad phenotype “cancer‐related fatigue” we were able to delineate subgroups characterized by biomarkers or history of depression. Future investigations may take these subtypes into account, ultimately enabling a better targeted therapy of fatigue.
What's new?
Fatigue associated with cancer frequently persists years after treatment, often with consequences for quality of life. Moreover, fatigue is commonly treated in an undifferentiated manner, owing to a lack of knowledge of possible fatigue subtypes and related markers. Here, the authors investigated the possibility of delineating fatigue subtypes according to biomarkers and psychological factors. Analyses reveal the existence of three fatigue subgroups: one distinguished by history of depression, another by high levels of inflammatory markers, and the third by high leptin levels. Consideration of potential fatigue subtypes could enable the development of targeted and more effective treatment options.
Background
The number of elderly cancer survivors is growing because of increasing survival rates. A high comorbidity burden in the elderly can affect their quality of life and survival. The aim of ...this study was to examine whether breast cancer survivors and population‐based controls have a different comorbidity burden after long‐term follow‐up.
Methods
This study used data from a German breast cancer case‐control study, which initially comprised 3813 breast cancer cases aged 50 to 74 years who were diagnosed between 2002 and 2005 and 7341 population‐based controls. Participants were followed up in 2014/2016. A modified Charlson Comorbidity Index (mCCI) was calculated to quantify severe comorbidities. Negative binomial regression was performed to estimate rate ratios (RRs) with 95% confidence intervals (CIs) for the association between case‐control status and mCCI (dependent variable) for the baseline population and for those who participated at follow‐up, with adjustments made for relevant lifestyle factors.
Results
In total, 1925 cases and 3674 controls participated in the follow‐up 12 years after recruitment. In the baseline population 35% had at least 1 comorbid condition.In long‐term survivors this proportion was 52%. No difference was found in the mCCI between breast cancer cases and controls at baseline (RR, 1.05; 95% CI, 0.98‐1.11) or between long‐term survivors of the 2 groups at baseline (RR, 1.07; 95% CI, 0.97‐1.18) or at follow‐up (RR, 1.00; 95% CI, 0.91‐1.10).
Conclusions
The comorbidity burden of long‐term breast cancer survivors and controls increased over time; however, it remained similar in both groups after 12 years of follow‐up.
The comorbidity burden does not differ between breast cancer cases and controls at recruitment (rate ratio RR, 1.05; 95% confidence interval CI, 0.98‐1.11). Even after 12 years of follow‐up, there is no difference in the comorbidity burden of long‐term breast cancer survivors and the control group (RR, 1.00; 95% CI, 0.91‐1.10).
More women are surviving after breast cancer due to early detection and modern treatment strategies. Body weight also influences survival. We aimed to characterize associations between postdiagnosis ...weight change and prognosis in postmenopausal long‐term breast cancer survivors. We used data from a prospective population‐based patient cohort study (MARIE) conducted in two geographical regions of Germany. Breast cancer patients diagnosed 50 to 74 years of age with an incident invasive breast cancer or in situ tumor were recruited from 2002 to 2005 and followed up until June 2015. Baseline weight was ascertained at an in‐person interview at recruitment and follow‐up weight was ascertained by telephone interview in 2009. Delayed entry Cox proportional hazards regression was used to assess associations between relative weight change and all‐cause mortality, breast cancer mortality, and recurrence‐free survival. In total, 2216 patients were included. Compared to weight maintenance (within 5%), weight loss >10% increased risk of all‐cause mortality (HR 2.50, 95% CI 1.61, 3.88), breast cancer mortality (HR 3.07, 95% CI 1.69, 5.60) and less so of recurrence‐free survival (HR 1.43, 95% CI 0.87, 2.36). Large weight gain of >10% also increased all‐cause mortality (HR 1.64, 95% CI 1.02, 2.62) and breast cancer mortality (HR 2.25, 95% CI 1.25, 4.04). Weight maintenance for up to 5 years in long‐term breast cancer survivors may help improve survival and prognosis. Postdiagnosis fluctuations in body weight of greater than 10% may lead to increased mortality. Survivors should be recommended to avoid large deviations in body weight from diagnosis onwards to maintain health and prolong life.
What's new?
Weight change, while common among breast cancer survivors, may not be optimal for survival. Here, the authors offer the first evaluation of the associations between post‐diagnosis weight change and subsequent prognosis in postmenopausal long‐term breast cancer survivors within a European setting. The results show that weight maintenance for up to 5 years after diagnosis is associated with better survival and prognosis, while fluctuations of more than 10% of body weight are associated with increased mortality. Encouraging breast cancer survivors to maintain weight after diagnosis may possibly help them to maintain a healthy and prolonged life.
Increasing evidence shows physical activity to be associated with improved colorectal cancer (CRC) prognosis. However, large‐scale prospective patient cohorts, comprehensively ascertaining physical ...activity, comprehensively considering potential variation by CRC stage and considering specific outcome measures, are sparse. Therefore, we aimed to evaluate the association of lifetime and latest prediagnostic leisure time physical activity with relevant prognostic outcomes in a large population‐based cohort of CRC patients. 3,121 patients, diagnosed with CRC in 2003–2010 (median age: 69 years), were interviewed on sociodemographic and lifestyle factors, medication and comorbidities. Cancer recurrence, vital status and cause of death were documented over a median follow‐up time of 4.8 years. Associations between lifetime and latest prediagnostic leisure time physical activity and overall, CRC‐specific, recurrence‐free and disease‐free survival were evaluated with Cox regression. Latest but not lifetime leisure time physical activity in metabolic task hours per week (MET‐h/wk) was associated with decreased overall and CRC‐specific mortality (>56.2 vs. ≤13.2 MET‐h/wk: adjusted hazard ratio (aHR)Overall/latest = 0.75; 95% confidence interval (CI) = 0.61–0.91; aHRCRC‐specific/latest = 0.81; 95% CI = 0.64–1.02). In particular lifetime and latest walking were associated with decreased mortality (>20 vs. 0–10 MET‐h/wk of walking: aHROverall/latest = 0.66; 95% CI = 0.56–0.77; aHRCRC‐specific/latest = 0.72; 95% CI = 0.60–0.87; aHROverall/lifetime = 0.78; 95% CI = 0.66–0.93; aHRCRC‐specific/lifetime = 0.71; 95% CI = 0.58–0.86). Associations were particularly pronounced for lifetime walking in metastatic (stage IV) and for latest walking in nonmetastatic disease patients. Prediagnostic physical activity was associated with improved CRC prognosis. Associations might be restricted to certain activities or depend on (non)metastatic disease state. Further optimization of activity recommendations and increase of recommendation adherence may help to improve patients' prognosis.
What's new?
Physical activity before and after colorectal cancer (CRC) diagnosis has previously been associated with improved prognosis. It remains unclear, however, whether those benefits can be attributed to specific types or intensities of activity. Here, in a cohort of 3,121 CRC patients, increased leisure time physical activity prior to CRC diagnosis was associated with reduced mortality postdiagnosis. The relationship was especially strong for lifetime walking in stage IV patients and latest walking in patients with nonmetastatic disease. Associations between CRC prognosis and physical activity may be influenced by activity type and disease state, potentially allowing for the optimization of activity recommendations and the improvement of recommendation adherence, in order to enhance patients' prognosis.
Background
Modifiable lifestyle factors are known to impact survival. It is less clear whether this differs between postmenopausal women ever diagnosed with breast cancer and unaffected women.
...Methods
Women diagnosed with breast cancer and unaffected women of comparable age were recruited from 2002 to 2005 and followed up until 2020. Using baseline information, a lifestyle adherence score (range 0–8; categorized as low 0–3.74, moderate 3.75–4.74, and high ≥4.75) was created based on the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations. Cox regression and competing risks analysis were used to analyze the association of adherence to WCRF/AICR lifestyle recommendations with overall mortality and with death due to cardiovascular diseases and cancer, respectively.
Results
A total of 8584 women were included (2785 with breast cancer and 5799 without). With a median follow‐up of 16.1 years there were 2006 total deaths. Among the deaths of known causes (98.6%), 445 were cardiovascular‐related and 1004 were cancer‐related. The average lifestyle score was 4.2. There was no differential effect of lifestyle score by case‐control status on mortality. After adjusting for covariates, moderate (hazard ratio HR, 0.66; 95% confidence interval CI, 0.57–0.76) and high (HR, 0.54; 95% CI, 0.47–0.63) adherence to WCRF/AICR lifestyle recommendations were significantly associated with a decrease in overall mortality. Similarly, in competing risks analysis, moderate and high adherence were associated with decreased mortality from cardiovascular diseases and from cancer.
Conclusions
A healthy lifestyle can substantially reduce mortality risk in women. With low adherence to all WCRF/AICR guidelines in about a third of study participants, health interventions are warranted.
There was no differential effect of a breast cancer diagnosis on the association between healthy lifestyle score and lower mortality in postmenopausal women.
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