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1.
J Natl Cancer Inst ; 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35026030

RESUMO

BACKGROUND: Incidence of colorectal cancer (CRC) among individuals aged less than 50 years has been increasing. As screening guidelines lower the recommended age of screening initiation, concerns including the burden on screening capacity and costs have been recognized, suggesting that an individualized approach may be warranted. We developed risk prediction models for early-onset CRC that incorporate an environmental risk score (ERS), including 16 lifestyle and environmental factors, and a polygenic risk score (PRS), of 141 variants. METHODS: Relying on risk score weights for ERS and PRS derived from studies of CRC at all ages, we evaluated risks for early-onset CRC in 3,486 cases and 3,890 controls aged less than 50 years. Relative and absolute risks for early-onset CRC were assessed according to values of the ERS and PRS. The discriminatory performance of these scores was estimated using the covariate-adjusted area under the receiver operating characteristic curve. RESULTS: Increasing values of ERS and PRS were associated with increasing relative risks for early-onset CRC (odds ratio per standard deviation of ERS = 1.14, 95% confidence interval [CI] = 1.08, 1.20; odds ratio per standard deviation of PRS = 1.59, 95% CI = 1.51, 1.68), both contributing to case-control discrimination (area under the curve = 0.631, 95% CI = 0.615, 0.647). Based on absolute risks, we can expect 26 excess cases per 10,000 men and 21 per 10,000 women, among those scoring at the 90th percentile for both risk scores. CONCLUSIONS: Personal risk scores have the potential to identify individuals at differential relative and absolute risk for early-onset CRC. Improved discrimination may aid in targeted CRC screening of younger, high-risk individuals, potentially improving outcomes.

2.
Sci Rep ; 12(1): 127, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996992

RESUMO

Identification of new genetic markers may improve the prediction of colorectal cancer prognosis. Our objective was to examine genome-wide associations of germline genetic variants with disease-specific survival in an analysis of 16,964 cases of colorectal cancer. We analyzed genotype and colorectal cancer-specific survival data from a consortium of 15 studies. Approximately 7.5 million SNPs were examined under the log-additive model using Cox proportional hazards models, adjusting for clinical factors and principal components. Additionally, we ran secondary analyses stratifying by tumor site and disease stage. We used a genome-wide p-value threshold of 5 × 10-8 to assess statistical significance. No variants were statistically significantly associated with disease-specific survival in the full case analysis or in the stage-stratified analyses. Three SNPs were statistically significantly associated with disease-specific survival for cases with tumors located in the distal colon (rs698022, HR = 1.48, CI 1.30-1.69, p = 8.47 × 10-9) and the proximal colon (rs189655236, HR = 2.14, 95% CI 1.65-2.77, p = 9.19 × 10-9 and rs144717887, HR = 2.01, 95% CI 1.57-2.58, p = 3.14 × 10-8), whereas no associations were detected for rectal tumors. Findings from this large genome-wide association study highlight the potential for anatomical-site-stratified genome-wide studies to identify germline genetic risk variants associated with colorectal cancer-specific survival. Larger sample sizes and further replication efforts are needed to more fully interpret these findings.

3.
Artigo em Inglês | MEDLINE | ID: mdl-35060941

RESUMO

INTRODUCTION: Prevalence of colorectal neoplasms varies by polygenic risk scores (PRS). We aimed to assess to what extent PRS might be relevant for defining personalized cutoff values for fecal immunochemical tests (FITs) in colorectal cancer (CRC) screening. METHODS: Among 5,306 participants of screening colonoscopy who provided a stool sample for a quantitative FIT (Ridascreen Hemoglobin or FOB Gold) prior to colonoscopy a PRS was determined, based on the number of risk alleles in 140 , single nucleotide polymorphism. Subjects were classified into low, medium and high genetic risk for colorectal neoplasms according to PRS tertiles. We calculated positive predictive values (PPVs) and numbers needed to scope (NNS) to detect one advanced neoplasm (AN) by risk group, and cutoff variation needed to achieve comparable PPVs across risk groups in the samples tested with Ridascreen (N=1,271) and FOB Gold (N=4,035) independently, using cutoffs yielding 85%, 90% or 95% specificity. RESULTS: Performance of both FITs was very similar within each PRS group. For a given cutoff, PPVs were consistently higher by 11%-15% units in the high-risk PRS group compared to the low-risk group (all P-values <0.05). Correspondingly, numbers needed to scope (NNS) to detect one advanced neoplasm varied from 2 (high PRS, high cutoff) to 5 (low PRS, low cutoff). Conversely, very different FIT cutoffs would be needed to ensure comparable PPVs across PRS groups. DISCUSSION: PPVs and NNS of FITs varied widely across people with high and low genetic risk score. Further research should evaluate the relevance of these differences for personalized CRC screening. FUNDING SOURCE: This study was partly funded by grants from the German Research Council (DFG, grant No. BR1704/16-1), the Federal Ministry of Education and Research (BMBF, grant no. 01GL1712), and the German Cancer Aid (No. 70113330).

4.
J Natl Compr Canc Netw ; : 1-11, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34875626

RESUMO

BACKGROUND: Colorectal cancer (CRC) survivors generally have a higher healthcare utilization (HCU) than the general population due to cancer burden. However, it is unclear which factors are associated with this increased uptake. Our study aimed to (1) compare CRC-related and non-CRC visits to general practitioners (GPs) and medical specialists (MSs) by comorbidities, and (2) assess whether HCU differs by demographic, clinical, and psychological factors. METHODS: We used data from a German population-based cohort of 1,718 survivors of stage I-III CRC diagnosed in 2003 through 2010 who provided information on HCU at 5-year follow-up. Multivariable linear regression was used to calculate least-square means of CRC-related and non-CRC HCU according to the Charlson comorbidity index and comorbidity cluster, adjusting for relevant demographic, clinical, and psychological characteristics. RESULTS: A higher comorbidity level was associated with more CRC-related MS visits and non-CRC GP visits. In addition to being strongly associated with non-CRC GP visits, comorbidity clusters were associated with CRC-related GP and MS visits, but their association varied by specific cardiometabolic comorbidities. HCU was less dependent on prognostic factors for CRC, such as age and tumor stage, but was strongly associated with disease recurrence, depression, and emotional functioning. CONCLUSIONS: Comorbidities, rather than age or tumor stage, were related to HCU, suggesting that CRC survivors use healthcare mainly for reasons other than cancer 5 years postdiagnosis. Improved communication between primary and tertiary healthcare providers could enhance the medical care of cancer survivors with complex health needs and thereby also reduce healthcare costs.

5.
Int J Cancer ; 2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34888857

RESUMO

Elevated blood levels of C-reactive protein (CRP) have been linked to colorectal cancer (CRC) survival. We evaluated genetic variants associated with CRP levels and their interactions with sex and lifestyle factors in association with CRC-specific mortality. This study included 16,142 CRC cases from the International Survival Analysis in Colorectal Cancer Consortium. We identified 618 common single nucleotide polymorphisms (SNPs) associated with CRP levels from the NHGRI-EBI GWAS Catalog. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between SNPs and CRC-specific mortality adjusting for age, sex, genotyping platform/study, and principal components. We investigated their interactions with sex and lifestyle factors using likelihood ratio tests. Of 5,472 (33.9%) deaths accrued over up to 10 years of follow-up, 3,547 (64.8%) were due to CRC. No variants were associated with CRC-specific mortality after multiple comparison correction. We observed strong evidence of interaction between variant rs1933736 at FRK gene and sex in relation to CRC-specific mortality (corrected Pinteraction = 0.0004); women had higher CRC-specific mortality associated with the minor allele (HR = 1.11, 95% CI = 1.04 to 1.19) whereas an inverse association was observed for men (HR = 0.88, 95% CI = 0.82 to 0.94). There was no evidence of interactions between CRP-associated SNPs and alcohol, obesity or smoking. Our study observed a significant interaction between sex and a CRP-associated variant in relation to CRC-specific mortality. Future replication of this association and functional annotation of the variant are needed.

6.
Int J Cancer ; 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34888862

RESUMO

For individuals willing to minimize their lifetime risk of colorectal cancer (CRC), the most effective screening approach remains unclear. Here, we sought to compare the long-term performance of existing and alternative CRC screening offers in a case study for Germany. Applying the perspective of a perfectly adhering man or woman at average risk, we used COSIMO, a validated Markov-based multistate model, to simulate the effects of current CRC screening offers in Germany. These include age- and sex-dependent offers for fecal immunochemical testing (FIT) or screening colonoscopy, which may be used twice starting at age 50 in men and age 55 in women. For comparison, we modelled screening colonoscopies at ages 50, 60 and 70, screening colonoscopies at ages 50 and 60, followed by biennial FITs, and conventional FIT-based strategies at varying intervals. We found that the highest reductions in lifetime risks of developing (76-84%) and dying from CRC (82-90%) were achieved by three colonoscopies, followed by annual FIT screening and strategies combining both modalities. In men, additional screening from age 70 onwards reduced the risk of dying from CRC by another 9% units and resulted in 32-39 additional life-years-gained per 1,000 individuals. Among women, three colonoscopies outperformed current screening offers in all outcomes, at little risk of screening-related complications. In summary, several FIT- and colonoscopy-based offers yield comparably high CRC risk reductions, including approaches combining both modalities. German screening offers may be optimized by lowering the eligibility age for screening colonoscopy for women, along with additional offers for the elderly.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34862210

RESUMO

BACKGROUND: Associations between candidate genetic variants and treatment outcomes of oxaliplatin, a drug commonly used for colorectal cancer patients, have been reported but not robustly established. This study aimed to validate previously reported prognostic and predictive genetic markers for oxaliplatin treatment outcomes and evaluate additional putative functional variants. METHODS: Fifty-three SNPs were selected based on previous reports (40 SNPs) or putative function in candidate genes (13 SNPs). We used data from 1,502 stage II-IV colorectal cancer patients who received primary adjuvant chemotherapy, 37% of whom received oxaliplatin treatment. Multivariable Cox proportional hazards models for overall survival and progression-free survival were applied separately in stage II-III and stage IV patients. For predictive SNPs, differential outcomes according to the type of chemotherapy (oxaliplatin-based vs. others) were evaluated using an interaction term. For prognostic SNPs, the association was assessed solely in patients with oxaliplatin-based treatment. RESULTS: Twelve SNPs were predictive and/or prognostic at P<0.05 with differential survival based on the type of treatment, in stage II-III patients (GSTM5-rs11807, ERCC2-rs13181, ERCC2-rs1799793, ERCC5-rs2016073, XPC-rs2228000, P2RX7-rs208294, HMGB1-rs1360485) and in stage IV patients (GSTM5-rs11807, MNAT1-rs3783819, MNAT1-rs4151330, CXCR1-rs2234671, VEGFA-rs833061, P2RX7-rs2234671). Additionally, five novel putative functional SNPs were identified to be predictive (ATP8B3-rs7250872, P2RX7-rs2230911, RPA1-rs5030755, MGMT-rs12917, P2RX7-rs2227963). CONCLUSION: Some SNPs yielded prognostic and/or predictive associations significant at P<0.05, however, none of the associations remained significant after correction for multiple testing. IMPACT: We did not robustly confirm previously reported SNPs despite some suggestive findings but identified further potential predictive SNPs, which warrant further investigation in well-powered studies.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34874489

RESUMO

PURPOSE: In Germany, almost every other colorectal cancer (CRC) patient undergoes inpatient cancer rehabilitation (ICR), but research on long-term outcomes is sparse. We aimed to assess health-related quality of life (HRQOL), distress, and posttraumatic growth among former rehabilitants and non-rehabilitants as well as respective differences and to estimate disease-related quality of life deficits in both groups. METHODS: HRQOL (EORTC-QLQ-C30/CR29), distress (QSC-R10), and posttraumatic growth (PTGI) were assessed according to past ICR in patients 5-year post-CRC-diagnosis in the German DACHS study. Least square mean differences in HRQOL scores and elevated distress levels (QSC-R10 > 14 points) by ICR were estimated by confounder-adjusted linear and logistic regression, respectively. Differences in PTGI scales were tested for statistical significance. EORTC-QLQ-C30 reference scores from population controls were accessed from the LinDE study to estimate disease-related deficits in both treatment groups. RESULTS: 49% of the included 1906 CRC survivors had undergone ICR. Rehabilitants reported lower HRQOL scores than non-rehabilitants in several dimensions of the EORTC-QLQ-C30/CR29. Differences were pronounced among younger survivors (< 70 years). In younger survivors, past ICR also predicted elevated distress. However, rehabilitants showed higher posttraumatic growth. When compared to 934 population controls, non-rehabilitants and older rehabilitants reported HRQOL scores (EORTC-QLQ-C30) similar to controls except higher levels of bowel dysfunctions, whereas younger rehabilitants experienced deficits regarding most scales (13/15). CONCLUSION: Our findings suggest a high disease burden 5 years after diagnosis in particular among younger CRC survivors who had undergone ICR. Observed HRQOL deficits are possibly linked to the initial indication for ICR and rehabilitants may benefit from effective follow-up concepts after ICR.

9.
Gastroenterology ; 2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34914944

RESUMO

BACKGROUND AND AIMS: Incidence of colorectal cancer (CRC) in younger adults is increasing in many countries. Given the established association of body mass index (BMI) with CRC risk and the increasing obesity prevalence among younger generations, we aimed to evaluate the association of BMI at different ages during early adulthood with early-onset CRC. METHODS: Among 6602 CRC patients and 7950 matched controls who were recruited in 2003-2020 in the DACHS study, a population-based case-control study from Germany, 747 patients and 621 controls were below age 55 and included in this analysis. Self-reported height and weight at ages 20 and 30 years, and at approximately 10 years before diagnosis or interview were recorded in personal interviews. Associations of BMI with early-onset CRC were estimated using multiple logistic regression. RESULTS: Compared to participants with BMI <25 kg/m2, those with BMI ≥30 kg/m2 (obesity) at age 20 and 30 years and approximately 10 years before diagnosis/interview had 2.56 (95% CI 1.20-5.44), 2.06 (1.25-3.40), and 1.88 (1.30-2.73) fold risk of early-onset CRC. The association of BMI with early-onset CRC risk was particularly pronounced among and essentially restricted to the majority of participants with no previous colonoscopy. CONCLUSION: Obesity at early adulthood is strongly associated with increased risk of early- onset CRC.

10.
Dtsch Arztebl Int ; 118(39): 664, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34919050
12.
JNCI Cancer Spectr ; 5(5): pkab077, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34738070

RESUMO

Background: Smoking has been associated with colorectal cancer (CRC) incidence and mortality in previous studies, but current evidence on smoking in association with survival after CRC diagnosis is limited. Methods: We pooled data from 12 345 patients with stage I-IV CRC from 11 epidemiologic studies in the International Survival Analysis in Colorectal Cancer Consortium. Cox proportional hazards regression models were used to evaluate the associations of prediagnostic smoking behavior with overall, CRC-specific, and non-CRC-specific survival. Results: Among 12 345 patients with CRC, 4379 (35.5%) died (2515 from CRC) over a median follow-up time of 7.5 years. Smoking was strongly associated with worse survival in stage I-III patients, whereas no association was observed among stage IV patients. Among stage I-III patients, clear dose-response relationships with all survival outcomes were seen for current smokers. For example, current smokers with 40 or more pack-years had statistically significantly worse overall, CRC-specific, and non-CRC-specific survival compared with never smokers (hazard ratio [HR] =1.94, 95% confidence interval [CI] =1.68 to 2.25; HR = 1.41, 95% CI = 1.12 to 1.78; and HR = 2.67, 95% CI = 2.19 to 3.26, respectively). Similar associations with all survival outcomes were observed for former smokers who had quit for less than 10 years, but only a weak association with non-CRC-specific survival was seen among former smokers who had quit for more than 10 years. Conclusions: This large consortium of CRC patient studies provides compelling evidence that smoking is strongly associated with worse survival of stage I-III CRC patients in a clear dose-response manner. The detrimental effect of smoking was primarily related to noncolorectal cancer events, but current heavy smoking also showed an association with CRC-specific survival.

14.
Eur J Cancer ; 157: 464-473, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34649117

RESUMO

BACKGROUND: Lymph node status is a prognostic marker and strongly influences therapeutic decisions in colorectal cancer (CRC). OBJECTIVES: The objective of the study is to investigate whether image features extracted by a deep learning model from routine histological slides and/or clinical data can be used to predict CRC lymph node metastasis (LNM). METHODS: Using histological whole slide images (WSIs) of primary tumours of 2431 patients in the DACHS cohort, we trained a convolutional neural network to predict LNM. In parallel, we used clinical data derived from the same cases in logistic regression analyses. Subsequently, the slide-based artificial intelligence predictor (SBAIP) score was included in the regression. WSIs and data from 582 patients of the TCGA cohort were used as the external test set. RESULTS: On the internal test set, the SBAIP achieved an area under receiver operating characteristic (AUROC) of 71.0%, the clinical classifier achieved an AUROC of 67.0% and a combination of the two classifiers yielded an improvement to 74.1%. Whereas the clinical classifier's performance remained stable on the TCGA set, performance of the SBAIP dropped to an AUROC of 61.2%. Performance of the clinical classifier depended strongly on the T stage. CONCLUSION: Deep learning-based image analysis may help predict LNM of patients with CRC using routine histological slides. Combination with clinical data such as T stage might be useful. Strategies to increase performance of the SBAIP on external images should be investigated.

15.
Clin Transl Gastroenterol ; 12(9): e00399, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34506306

RESUMO

INTRODUCTION: The performance of colorectal cancer (CRC) screening programs depends on the adherence to screening offers. However, identical adherence levels may result from varying patterns of the population's screening behavior. We quantified the effects of different adherence patterns on the long-term performance of CRC screening for annual fecal immunochemical testing and screening colonoscopy at 10-year intervals. METHODS: Using a multistate Markov model, we simulated scenarios where, while at the same overall adherence level, a certain proportion of the population adheres to all screening offers (selective adherence) or the entire population uses the screening offers at some point(s) of time, albeit not in the recommended frequency (sporadic adherence). Key outcomes for comparison were the numbers of prevented CRC cases and prevented CRC deaths after 50 simulated years. RESULTS: For screening with annual fecal immunochemical testing at adherence levels of 10%-50%, ratios of prevented CRC cases (CRC deaths) resulting from a sporadic vs a selective pattern ranged from 1.8 to 4.4 (1.9-5.3) for men and from 1.7 to 3.6 (1.8-4.4) for women, i.e., up to 4-5 times more CRC cases and deaths were prevented when the population followed a sporadic instead of a selective adherence pattern. Comparisons of simulated scenarios for screening colonoscopy revealed similar patterns. DISCUSSION: Over a lifelong time frame, large numbers of irregular screening attendees go along with much larger preventive effects than small numbers of perfectly adhering individuals. In clinical practice, efforts to reach as many people as possible at least sporadically should be prioritized over efforts to maximize adherence to repeat screening offers.

16.
Oncologist ; 26(12): e2170-e2180, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34476870

RESUMO

BACKGROUND: In geriatric oncology, polypharmacy is often assessed during a comprehensive geriatric assessment. Previous studies about its association with survival among patients with colorectal cancer (CRC) were inconclusive and had high risk for indication bias. PATIENTS AND METHODS: A cohort study was conducted with 3,239 patients with CRC, aged ≥65 years, who were recruited in Germany between 2003 and 2016, while being hospitalized for CRC surgery. We defined polypharmacy as the concurrent use of five or more drugs, and excessive polypharmacy (EPP) as concurrent use of eight or more drugs. Cox proportional hazards regression models were performed to assess the associations of polypharmacy with 5-year overall (OS), CRC-specific (CSS), and non-cancer-specific survival (NCS) with rigorous adjustment for morbidity to minimize indication bias (e.g., for cancer stage, functional status, and 13 common diseases/conditions). RESULTS: The prevalence of polypharmacy was 54.7% and that of EPP was 24.2%. During up to 5 years of follow-up, 1,070 participants died, among whom 615 died of CRC and 296 died of other causes than cancer. EPP was statistically significantly associated with poorer up-to-5-year OS (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.02-1.47) and CSS (HR, 1.31; 95% CI, 1.03-1.68). HR point estimate for NCS was higher than 1 (1.22) but not statistically significant. CONCLUSION: Polypharmacy was very common and EPP was a weak risk factor for mortality in this large cohort of older patients with CRC. Clinical trials are needed to address the causality of this relationship because older patients with CRC might benefit from deprescribing drugs without an indication. IMPLICATIONS FOR PRACTICE: The results of this study support the hypothesis that excessive polypharmacy, defined as use of eight or more concurrently used active substances, has a negative impact on the prognosis of older patients with colorectal cancer (CRC). This study suggests to oncologists that performing a medication review for older patients with CRC with eight drugs or more is indicated (especially when a broader comprehensive geriatric assessment is being performed). Such a medication review should not only focus on reducing the number of medications (by deprescribing drugs without an indication) but also check the appropriateness of indicated drugs for older patients with cancer.

17.
J Pathol ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34561876

RESUMO

Deep learning is a powerful tool in computational pathology: it can be used for tumor detection and for predicting genetic alterations based on histopathology images alone. Conventionally, tumor detection and prediction of genetic alterations are two separate workflows. Newer methods have combined them, but require complex, manually engineered computational pipelines, restricting reproducibility and robustness. To address these issues, we present a new method for simultaneous tumor detection and prediction of genetic alterations: The Slide-Level Assessment Model (SLAM) uses a single off-the-shelf neural network to predict molecular alterations directly from routine pathology slides without any manual annotations, improving upon previous methods by automatically excluding normal and non-informative tissue regions. SLAM requires only standard programming libraries and is conceptually simpler than previous approaches. We have extensively validated SLAM for clinically relevant tasks using two large multicentric cohorts of colorectal cancer patients, Darmkrebs: Chancen der Verhütung durch Screening (DACHS) from Germany and Yorkshire Cancer Research Bowel Cancer Improvement Programme (YCR-BCIP) from the UK. We show that SLAM yields reliable slide-level classification of tumor presence with an area under the receiver operating curve (AUROC) of 0.980 (confidence interval 0.975, 0.984; n = 2,297 tumor and n = 1,281 normal slides). In addition, SLAM can detect microsatellite instability (MSI)/mismatch repair deficiency (dMMR) or microsatellite stability/mismatch repair proficiency with an AUROC of 0.909 (0.888, 0.929; n = 2,039 patients) and BRAF mutational status with an AUROC of 0.821 (0.786, 0.852; n = 2,075 patients). The improvement with respect to previous methods was validated in a large external testing cohort in which MSI/dMMR status was detected with an AUROC of 0.900 (0.864, 0.931; n = 805 patients). In addition, SLAM provides human-interpretable visualization maps, enabling the analysis of multiplexed network predictions by human experts. In summary, SLAM is a new simple and powerful method for computational pathology that could be applied to multiple disease contexts. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

18.
JNCI Cancer Spectr ; 5(4): pkab056, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34377935

RESUMO

Background: Smoking is associated with colorectal cancer (CRC) risk. Previous studies suggested this association may be restricted to certain molecular subtypes of CRC, but large-scale comprehensive analysis is lacking. Methods: A total of 9789 CRC cases and 11 231 controls of European ancestry from 11 observational studies were included. We harmonized smoking variables across studies and derived sex study-specific quartiles of pack-years of smoking for analysis. Four somatic colorectal tumor markers were assessed individually and in combination, including BRAF mutation, KRAS mutation, CpG island methylator phenotype (CIMP), and microsatellite instability (MSI) status. A multinomial logistic regression analysis was used to assess the association between smoking and risk of CRC subtypes by molecular characteristics, adjusting for age, sex, and study. All statistical tests were 2-sided and adjusted for Bonferroni correction. Results: Heavier smoking was associated with higher risk of CRC overall and stratified by individual markers (P trend < .001). The associations differed statistically significantly between all molecular subtypes, which was the most statistically significant for CIMP and BRAF. Compared with never-smokers, smokers in the fourth quartile of pack-years had a 90% higher risk of CIMP-positive CRC (odds ratio = 1.90, 95% confidence interval = 1.60 to 2.26) but only 35% higher risk for CIMP-negative CRC (odds ratio = 1.35, 95% confidence interval = 1.22 to 1.49; P difference = 2.1 x 10-6). The association was also stronger in tumors that were CIMP positive, MSI high, or KRAS wild type when combined (P difference < .001). Conclusion: Smoking was associated with differential risk of CRC subtypes defined by molecular characteristics. Heavier smokers had particularly higher risk of CRC subtypes that were CIMP positive and MSI high in combination, suggesting that smoking may be involved in the development of colorectal tumors via the serrated pathway.

19.
Eur J Cancer ; 155: 200-215, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34391053

RESUMO

BACKGROUND: Gastrointestinal cancers account for approximately 20% of all cancer diagnoses and are responsible for 22.5% of cancer deaths worldwide. Artificial intelligence-based diagnostic support systems, in particular convolutional neural network (CNN)-based image analysis tools, have shown great potential in medical computer vision. In this systematic review, we summarise recent studies reporting CNN-based approaches for digital biomarkers for characterization and prognostication of gastrointestinal cancer pathology. METHODS: Pubmed and Medline were screened for peer-reviewed papers dealing with CNN-based gastrointestinal cancer analyses from histological slides, published between 2015 and 2020.Seven hundred and ninety titles and abstracts were screened, and 58 full-text articles were assessed for eligibility. RESULTS: Sixteen publications fulfilled our inclusion criteria dealing with tumor or precursor lesion characterization or prognostic and predictive biomarkers: 14 studies on colorectal or rectal cancer, three studies on gastric cancer and none on esophageal cancer. These studies were categorised according to their end-points: polyp characterization, tumor characterization and patient outcome. Regarding the translation into clinical practice, we identified several studies demonstrating generalization of the classifier with external tests and comparisons with pathologists, but none presenting clinical implementation. CONCLUSIONS: Results of recent studies on CNN-based image analysis in gastrointestinal cancer pathology are promising, but studies were conducted in observational and retrospective settings. Large-scale trials are needed to assess performance and predict clinical usefulness. Furthermore, large-scale trials are required for approval of CNN-based prediction models as medical devices.

20.
Am J Gastroenterol ; 116(11): 2173-2183, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34309586

RESUMO

INTRODUCTION: Incidence of colorectal cancer (CRC) in young adults has been increasing in recent decades in many countries for still widely unclear reasons. Suspected candidates include increasing prevalence of overweight and obesity, but specific evidence on their role for early-onset CRC (EOCRC) is sparse. We conducted a systematic review and meta-analysis to summarize available evidence on the association of body mass index (BMI) with EOCRC. METHODS: We systematically searched PubMed, EMBASE, and Web of Science up to February 2021 for studies that evaluated the association of BMI (before diagnosis but not near diagnosis) with CRC risk and reported specific results for EOCRC. Results from studies with similar BMI groupings were summarized in meta-analyses using random-effects models. RESULTS: Twelve studies were eligible and included. Results of 6 studies were pooled in meta-analyses, which yielded a higher risk of EOCRC for overweight and obesity (BMI ≥25 kg/m2) compared with normal weight (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.19-1.68). An increasing risk with increasing BMI was observed, with much higher risk for obesity (OR 1.88, 95% CI 1.40-2.54) than for overweight (OR 1.32, 95% CI 1.19-1.47). DISCUSSION: Obesity is a strong risk factor for EOCRC, and its increasing prevalence in younger generations is likely to substantially contribute to the increase in EOCRC. Efforts to limit the obesity epidemic in adolescents and younger adults may be crucial for reducing CRC incidence in future generations of adults.


Assuntos
Índice de Massa Corporal , Neoplasias Colorretais/epidemiologia , Idade de Início , Humanos , Medição de Risco
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