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2.
Gastrointest Endosc ; 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31521778

RESUMO

BACKGROUND AND AIMS: Guidelines recommend colonoscopy after an episode of diverticulitis to exclude neoplasia but the effectiveness of testing is uncertain. Patients with complicated diverticulitis may be at higher risk for neoplasia, but most patients have uncomplicated disease. We examined the incidence of colorectal cancer (CRC) and advanced adenoma (AA) in patients with diverticulitis compared with subjects undergoing screening colonoscopy. METHODS: Computed tomography (CT) scans from January 1, 2008 to May 1, 2013 at the University of Pittsburgh Medical Center (UPMC) were reviewed to identify subjects with confirmed acute diverticulitis. Subsequent surgical, colonoscopy, and pathology reports were abstracted for AA and CRC diagnoses. Neoplasia incidence was compared with that reported for screening colonoscopy from a meta-analysis (N=68,324), and from colonoscopy exams at UPMC between 2013 and 2015 (N=28,573). RESULTS: A total of 5167 abdominal/pelvic CT scan reports identified 978 patients with acute diverticulitis, among which 474 (48.5%) subjects had at least one colonoscopy or gastrointestinal surgery through April 2015. The CRC rate in patients with diverticulitis (13/474, 2.7%) was significantly higher (P<0.0001) compared with both the meta-analysis (0.8%) and UPMC (0.3%). The AA rate (19/474, 4.0%) was similar to the rate in the meta-analysis (5.0%, P=0.39) but significantly lower than at UPMC (7.7%, P=0.003). The incidence of AA or CRC in complicated diverticulitis (10/141, 7.1%) did not differ significantly (P=0.85) from the incidence of AA or CRC in uncomplicated diverticulitis (22/332, 6.6%). CONCLUSIONS: CRC after diverticulitis was significantly higher than that observed at screening colonoscopy and was not limited to complicated disease. Colonoscopy is advisable after the diagnosis of diverticulitis.

4.
Gastroenterology ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31394083

RESUMO

The incidence of colorectal cancer (CRC) is increasing worldwide. CRC has high mortality when detected at advanced stages, yet it is also highly preventable. Given the difficulties in implementing major lifestyle changes or widespread primary prevention strategies to decrease CRC risk, screening is the most powerful public health tool to reduce mortality. Screening methods are effective but have limitations. Furthermore, many screen-eligible persons remain unscreened. We discuss established and emerging screening methods, and potential strategies to address current limitations in CRC screening. A quantum step in CRC prevention might come with the development of new screening strategies, but great gains can be made by deploying the available CRC screening modalities in ways that optimize outcomes while making judicious use of resources.

5.
Front Immunol ; 10: 1401, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275327

RESUMO

Myeloid derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that accumulate in circulation of cancer patients and at tumor sites where they suppress anti-tumor immunity. We previously reported that in a colon cancer prevention trial of a MUC1 vaccine tested in individuals at increased risk for colon cancer, those who did not mount immune response to the vaccine had higher pre-vaccination levels of circulating MDSC compared to those who did. We also reported that individuals with pancreatic premalignancy, Intraductal Papillary Mucinous Neoplasm (IPMN), had increased circulating levels of MDSC that inversely correlated with spontaneous antibody responses against the pancreatic tumor associated antigen MUC1, abnormally expressed on IPMN. Accumulation of MDSC in cancer and their immunosuppressive role had been well established but their presence in premalignancy was unexpected. In this study we compared MDSC in premalignancy with those in cancer with the hypothesis that there might be differences in the composition of various MDSC subpopulations and their immunosuppressive functions due to different lengths of exposure to disease and/or different tissue microenvironments. In cohorts of patients with premalignant polyps, colon cancer, premalignant IPMN, and pancreatic cancer, we confirmed higher levels of MDSC in premalignancy compared to healthy controls, higher levels of MDSC in cancer compared to premalignancy, but no difference in their subpopulation composition or immunosuppressive capacity. We show that levels of MDSC in premalignancy correlate negatively in vivo with spontaneous MUC1-specific antibody responses and in vitro with polyclonal T cell proliferation and IFN-γ secretion.

6.
Int J Cancer ; 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31209889

RESUMO

Interindividual differences in DNA repair systems may play a role in modulating the individual risk of developing colorectal cancer. To better ascertain the role of DNA repair gene polymorphisms on colon and rectal cancer risk individually, we evaluated 15,419 single nucleotide polymorphisms (SNPs) within 185 DNA repair genes using GWAS data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), which included 8,178 colon cancer, 2,936 rectum cancer cases and 14,659 controls. Rs1800734 (in MLH1 gene) was associated with colon cancer risk (p-value = 3.5 × 10-6 ) and rs2189517 (in RAD51B) with rectal cancer risk (p-value = 5.7 × 10-6 ). The results had statistical significance close to the Bonferroni corrected p-value of 5.8 × 10-6 . Ninety-four SNPs were significantly associated with colorectal cancer risk after Binomial Sequential Goodness of Fit (BSGoF) procedure and confirmed the relevance of DNA mismatch repair (MMR) and homologous recombination pathways for colon and rectum cancer, respectively. Defects in MMR genes are known to be crucial for familial form of colorectal cancer but our findings suggest that specific genetic variations in MLH1 are important also in the individual predisposition to sporadic colon cancer. Other SNPs associated with the risk of colon cancer (e.g., rs16906252 in MGMT) were found to affect mRNA expression levels in colon transverse and therefore working as possible cis-eQTL suggesting possible mechanisms of carcinogenesis.

7.
Int J Cancer ; 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31037736

RESUMO

Alcohol consumption is an established risk factor for colorectal cancer (CRC). However, while studies have consistently reported elevated risk of CRC among heavy drinkers, associations at moderate levels of alcohol consumption are less clear. We conducted a combined analysis of 16 studies of CRC to examine the shape of the alcohol-CRC association, investigate potential effect modifiers of the association, and examine differential effects of alcohol consumption by cancer anatomic site and stage. We collected information on alcohol consumption for 14,276 CRC cases and 15,802 controls from 5 case-control and 11 nested case-control studies of CRC. We compared adjusted logistic regression models with linear and restricted cubic splines to select a model that best fit the association between alcohol consumption and CRC. Study-specific results were pooled using fixed-effects meta-analysis. Compared to non-/occasional drinking (≤1 g/day), light/moderate drinking (up to 2 drinks/day) was associated with a decreased risk of CRC (odds ratio [OR]: 0.92, 95% confidence interval [CI]: 0.88-0.98, p = 0.005), heavy drinking (2-3 drinks/day) was not significantly associated with CRC risk (OR: 1.11, 95% CI: 0.99-1.24, p = 0.08) and very heavy drinking (more than 3 drinks/day) was associated with a significant increased risk (OR: 1.25, 95% CI: 1.11-1.40, p < 0.001). We observed no evidence of interactions with lifestyle risk factors or of differences by cancer site or stage. These results provide further evidence that there is a J-shaped association between alcohol consumption and CRC risk. This overall pattern was not significantly modified by other CRC risk factors and there was no effect heterogeneity by tumor site or stage.

8.
Cancer Causes Control ; 30(8): 799-811, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31069578

RESUMO

An important premise of epidemiology is that individuals with the same disease share similar underlying etiologies and clinical outcomes. In the past few decades, our knowledge of disease pathogenesis has improved, and disease classification systems have evolved to the point where no complex disease processes are considered homogenous. As a result, pathology and epidemiology have been integrated into the single, unified field of molecular pathological epidemiology (MPE). Advancing integrative molecular and population-level health sciences and addressing the unique research challenges specific to the field of MPE necessitates assembling experts in diverse fields, including epidemiology, pathology, biostatistics, computational biology, bioinformatics, genomics, immunology, and nutritional and environmental sciences. Integrating these seemingly divergent fields can lead to a greater understanding of pathogenic processes. The International MPE Meeting Series fosters discussion that addresses the specific research questions and challenges in this emerging field. The purpose of the meeting series is to: discuss novel methods to integrate pathology and epidemiology; discuss studies that provide pathogenic insights into population impact; and educate next-generation scientists. Herein, we share the proceedings of the Fourth International MPE Meeting, held in Boston, MA, USA, on 30 May-1 June, 2018. Major themes of this meeting included 'integrated genetic and molecular pathologic epidemiology', 'immunology-MPE', and 'novel disease phenotyping'. The key priority areas for future research identified by meeting attendees included integration of tumor immunology and cancer disparities into epidemiologic studies, further collaboration between computational and population-level scientists to gain new insight on exposure-disease associations, and future pooling projects of studies with comparable data.

9.
Gastroenterology ; 157(1): 137-148, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30930021

RESUMO

BACKGROUND & AIMS: The American Cancer Society has recommended initiating colorectal cancer (CRC) screening at age 45 years instead of 50 years. We estimated the cost effectiveness and national effects of adopting this recommendation. METHODS: We compared screening strategies and alternative resource allocations in a validated Markov model. We based national projections on screening participation rates by age and census data. RESULTS: Screening colonoscopy initiation at age 45 years instead of 50 years in 1000 persons averted 4 CRCs and 2 CRC deaths, gained 14 quality-adjusted life-years (QALYs), cost $33,900/QALY gained, and required 758 additional colonoscopies. These 758 colonoscopies could instead be used to screen 231 currently unscreened 55-year-old persons or 342 currently unscreened 65-year-old persons, through age 75 years. These alternatives averted 13-14 CRC cases and 6-7 CRC deaths and gained 27-28 discounted QALYs while saving $163,700-$445,800. Improving colonoscopy completion rates after abnormal results from a fecal immunochemical test yielded greater benefits and savings. Initiation of fecal immunochemical testing at age 45 years instead of 50 years cost $7700/QALY gained. Shifting current age-specific screening rates to 5 years earlier could avert 29,400 CRC cases and 11,100 CRC deaths over the next 5 years but would require 10.7 million additional colonoscopies and cost an incremental $10.4 billion. Improving screening rates to 80% in persons who are 50-75 years old would avert nearly 3-fold more CRC deaths at one third the incremental cost. CONCLUSIONS: In a Markov model analysis, we found that starting CRC screening at age 45 years is likely to be cost effective. However, greater benefit, at lower cost, could be achieved by increasing participation rates for unscreened older and higher-risk persons.


Assuntos
Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Sangue Oculto , Fatores Etários , Idoso , American Cancer Society , Colonoscopia/economia , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Detecção Precoce de Câncer/economia , Feminino , Humanos , Imunoquímica/economia , Imunoquímica/métodos , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Anos de Vida Ajustados por Qualidade de Vida , Estados Unidos
10.
Gastrointest Endosc ; 89(4): 896-897, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30902210
11.
Cancer Res ; 79(6): 1191-1203, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30674532

RESUMO

Bromodomain and extraterminal domain (BET) family proteins such as BRD4 are epigenetic readers that control expression of a number of oncogenic proteins. Targeting this family of proteins has recently emerged as a promising anticancer approach. BET inhibitors (BETi), either alone or in combination with other anticancer agents, have exhibited efficacy in a variety of tumors. However, the molecular mechanisms underlying differential response to BETi are not well understood. In this study, we report that death receptor 5 (DR5), a key component of the extrinsic apoptotic pathway, is markedly induced in response to BRD4 depletion and BETi treatment in colorectal cancer cells. Induction of DR5, following BET inhibition, was mediated by endoplasmic reticulum stress and CHOP-dependent transcriptional activation. Enhanced DR5 induction was necessary for the chemosensitization and apoptotic effects of BETi and was responsible for increased BETi sensitivity in colorectal cancer cells containing a mutation in speckle-type POZ protein (SPOP), a subunit of BRD4 E3 ubiquitin ligase. In a colorectal cancer xenograft model, BETi combined with chemotherapy suppressed the tumor growth in a DR5-dependent manner and potently inhibited patient-derived xenograft tumor growth with enhanced DR5 induction and apoptosis. These findings suggest that BETi alone or in combination with chemotherapy is effective against colorectal cancer due to enhanced DR5 induction and apoptosis. DR5 induction may also serve as a useful marker for designing personalized treatment and improved colorectal cancer combination therapies.Significance: These findings reveal how BET inhibition sensitizes chemotherapy and kills a subset of colon cancer cells with specific genetic alterations and may provide a new molecular marker for improving colon cancer therapies.

12.
Artigo em Inglês | MEDLINE | ID: mdl-30502933

RESUMO

BACKGROUND: Screening flexible sigmoidoscopy reduces incidence and mortality of colorectal cancer. Previously reported results from the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) screening trial had a median follow-up of 12 years. Whether the benefit is sustained over the long term and remains so in both sexes and all age groups is uncertain. We report long-term results after an additional 5 years of follow-up. METHODS: Participants in the PLCO trial were recruited from the general population in the catchment areas of ten screening centres across the USA, without previous diagnosis of a prostate, lung, colorectal, or ovarian cancer or current cancer treatment. From 1993 to 2001, participants aged 55-74 years were randomly assigned to usual care or flexible sigmoidoscopy at baseline and again at 3 years or 5 years. Randomisation was done within blocks and stratified by centre, age, and sex. The primary endpoint was cause-specific mortality and secondary endpoints included incidence and tumour staging; cause of death was determined without knowledge of study arm. In this analysis, we assessed incidence and mortality rates overall, by time-period, and by combinations of sex, age at baseline (55-64 years/65-74 years), location (distal/proximal), and stage, on an intent-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT00002540. FINDINGS: After a median follow-up of 15·8 years (IQR 13·2-18·0) for incidence and 16·8 years (14·4-18·9) for mortality, the incidence of colorectal cancer was significantly lower in the intervention arm (1461 cases; 12·55 per 10 000 person-years) than with usual care (1761 cases; 15·33 per 10 000 person-years; relative risk [RR] 0·82, 95% CI 0·76-0·88). Similarly, mortality was lower in the intervention arm (417 deaths; 3·37 per 10 000 person-years) than the usual care arm (549; 4·48 per 10 000 person-years; RR 0·75, 95% CI 0·66-0·85). The reduction in mortality was limited to the distal colon, with no significant effect in the proximal colon. Reductions in incidence were significantly larger in men than women (pinteraction=0·04) and reductions in mortality were significantly larger in the older age group (65-74 years vs 55-64 years at baseline; pinteraction=0·01). INTERPRETATION: Reductions in colorectal cancer incidence and mortality from flexible sigmoidoscopy screening are sustained over the long term. Differences by sex and age should be examined in other ongoing trials of colorectal cancer screening to help clarify if different screening strategies would achieve greater risk reduction. FUNDING: Extended follow-up was funded under NIH contract HHSN261201600007I.

13.
PLoS One ; 13(10): e0206519, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30379922

RESUMO

BACKGROUND: High levels of serum leptin and low levels of serum adiponectin are strongly correlated with obesity, a well-established risk factor for colorectal cancer (CRC). Growing evidence suggests that dysregulation of leptin and adiponectin levels may play an etiological role in colorectal carcinogenesis. We evaluated 20 candidate variants in 4 genes previously shown to alter serum leptin and adiponectin levels for associations with obesity (BMI>30 kg/m2) and CRC risk. METHODS: We analyzed 6,246 CRC cases and 7,714 population-based controls from 11 studies within the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Associations of each variant with obesity or CRC were evaluated using multivariate logistic regression models stratified by sex and adjusted for age, a study variable, and the first three principal components of genetic ancestry. Gene-specific False Discovery Rate (FDR)-adjusted p-values <0.05 denoted statistical significance. RESULTS: Two variants in the leptin gene showed statistically significant associations with CRC among women: LEP rs2167270 (OR = 1.13, 95% CI: 1.06-1.21) and LEP rs4731426 (OR = 1.09, 95% CI: 1.02-1.17). These associations remained significant after adjustment for obesity, suggesting that leptin SNPs may influence CRC risk independent of obesity. We observed statistically significant interactions of the leptin variants with hormone replacement therapy (HRT) for CRC risk; these variant associations were strengthened when analyses were restricted to post-menopausal women with low estrogen exposure, as estimated by 'never use' of HRT and/or non-obese BMI. No variants were associated with CRC among men. CONCLUSIONS: Leptin gene variants may exhibit sex-specific associations with CRC risk. Endogenous and exogenous estrogen exposure may modify the association between these variants, leptin levels, and CRC risk.

14.
Int J Epidemiol ; 2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30476131

RESUMO

Background: Chronic inflammation is a risk factor for colorectal cancer (CRC). Circulating C-reactive protein (CRP) is also moderately associated with CRC risk. However, observational studies are susceptible to unmeasured confounding or reverse causality. Using genetic risk variants as instrumental variables, we investigated the causal relationship between genetically elevated CRP concentration and CRC risk, using a Mendelian randomization approach. Methods: Individual-level data from 30 480 CRC cases and 22 844 controls from 33 participating studies in three international consortia were used: the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT) and the Colon Cancer Family Registry (CCFR). As instrumental variables, we included 19 single nucleotide polymorphisms (SNPs) previously associated with CRP concentration. The SNP-CRC associations were estimated using a logistic regression model adjusted for age, sex, principal components and genotyping phases. An inverse-variance weighted method was applied to estimate the causal effect of CRP on CRC risk. Results: Among the 19 CRP-associated SNPs, rs1260326 and rs6734238 were significantly associated with CRC risk (P = 7.5 × 10-4, and P = 0.003, respectively). A genetically predicted one-unit increase in the log-transformed CRP concentrations (mg/l) was not associated with increased risk of CRC [odds ratio (OR) = 1.04; 95% confidence interval (CI): 0.97, 1.12; P = 0.256). No evidence of association was observed in subgroup analyses stratified by other risk factors. Conclusions: In spite of adequate statistical power to detect moderate association, we found genetically elevated CRP concentration was not associated with increased risk of CRC among individuals of European ancestry. Our findings suggested that circulating CRP is unlikely to be a causal factor in CRC development.

15.
Artigo em Inglês | MEDLINE | ID: mdl-30326300

RESUMO

BACKGROUND & AIMS: There is significant variation among endoscopists in their adenoma detection rates (ADRs). We explored associations between ADR and characteristics of endoscopists, including personality traits and financial incentives. METHODS: We collected electronic health record data from October 2013 through September 2015 and calculated ADRs for physicians from 4 health systems. ADRs were risk-adjusted for differences in patient populations. Physicians were surveyed to assess financial motivations, knowledge and perceptions about colonoscopy quality, and personality traits. Of 140 physicians sent the survey, 117 responded. RESULTS: The median risk-adjusted ADR for all surveyed physicians was 29.3% (interquartile range, 24.1%-35.5%). We found no significant association between ADR and financial incentives, malpractice concerns, or physicians' perceptions of ADR as a quality metric. ADR was associated with the degree of self-reported compulsiveness relative to peers: among endoscopists who described themselves as much more compulsive, the ADR was 33.1%; among those who described themselves as somewhat more compulsive, the ADR was 32.9%; among those who described themselves as about the same as others, the ADR was 26.4%; and among those who described themselves as somewhat less compulsive, the ADR was 27.3%) (P = .0019). ADR also associated with perceived thoroughness (much more thorough than peers, ADR = 31.5%; somewhat more, 31.9%; same/somewhat less, 27.1%; P = .0173). Physicians who reported feeling rushed, having difficulty pacing themselves, or having difficulty in accomplishing goals had higher ADRs. A secondary analysis found the same associations between personality and adenomas per colonoscopy. CONCLUSIONS: In a survey of endoscopists and comparison of results with ADRs, we found no significant association between ADR and financial incentives, malpractice concerns, or perceptions of ADR as a quality metric. However, ADRs were higher among physicians who described themselves as more compulsive or thorough, and among those who reported feeling rushed or having difficulty accomplishing goals.

17.
Dig Endosc ; 30(6): 750-759, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29971834

RESUMO

BACKGROUND AND AIMS: Different post-polypectomy guidelines underscore the need for high-quality baseline colonoscopy before appropriate surveillance recommendations can be made. Standards for colonoscopy practice have been advocated by gastrointestinal societies. Our aims were to define standards for the procedural practice of colonoscopy in this particular setting of surveillance and to generate a colonoscopy procedural quality checklist that could be implemented in clinical practice. METHODS: This study was based on the Delphi process methodology. The baseline questionnaire included 12 domains and 56 individual statements. A total of three rounds were carried out between September 2015 and March 2016 until consensus or lack of consensus was reached. RESULTS: In total, consensus was reached on 27 statements in nine domains. High levels of agreement and consensus were reached that: (i) colonoscopy should be considered complete only if the whole cecum has been inspected, including the ileocecal valve and the appendiceal orifice (agreement score 4.63; degree of consensus 82%); (ii) quality of the bowel preparation should always be reported (agreement score 4.9, degree of consensus 94%); and (iii) it is preferable to use a segmental validated scale (agreement score 4.36, degree of consensus 86%). Consensus was also reached regarding multiple statements related to documentation of polyps and their resection. Finally, a colonoscopy quality checklist was drafted. CONCLUSION: Consensus on different statements regarding quality of colonoscopy has been reached. Based on this consensus, we propose a colonoscopy quality checklist that would be helpful for post-polypectomy surveillance recommendations.

18.
Gastroenterology ; 155(3): 909-925.e3, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29958856

RESUMO

BACKGROUND & AIMS: Colonoscopy examination does not always detect colorectal cancer (CRC)- some patients develop CRC after negative findings from an examination. When this occurs before the next recommended examination, it is called interval cancer. From a colonoscopy quality assurance perspective, that term is too restrictive, so the term post-colonoscopy colorectal cancer (PCCRC) was created in 2010. However, PCCRC definitions and methods for calculating rates vary among studies, making it impossible to compare results. We aimed to standardize the terminology, identification, analysis, and reporting of PCCRCs and CRCs detected after other whole-colon imaging evaluations (post-imaging colorectal cancers [PICRCs]). METHODS: A 20-member international team of gastroenterologists, pathologists, and epidemiologists; a radiologist; and a non-medical professional met to formulate a series of recommendations, standardize definitions and categories (to align with interval cancer terminology), develop an algorithm to determine most-plausible etiologies, and develop standardized methodology to calculate rates of PCCRC and PICRC. The team followed the Appraisal of Guidelines for Research and Evaluation II tool. A literature review provided 401 articles to support proposed statements; evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. The statements were voted on anonymously by team members, using a modified Delphi approach. RESULTS: The team produced 21 statements that provide comprehensive guidance on PCCRCs and PICRCs. The statements present standardized definitions and terms, as well as methods for qualitative review, determination of etiology, calculation of PCCRC rates, and non-colonoscopic imaging of the colon. CONCLUSIONS: A 20-member international team has provided standardized methods for analysis of etiologies of PCCRCs and PICRCs and defines its use as a quality indicator. The team provides recommendations for clinicians, organizations, researchers, policy makers, and patients.


Assuntos
Colonoscopia/normas , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/normas , Guias de Prática Clínica como Assunto/normas , Colo/diagnóstico por imagem , Colonoscopia/métodos , Consenso , Detecção Precoce de Câncer/métodos , Humanos , Fatores de Risco , Fatores de Tempo
19.
Cancer Res ; 78(16): 4790-4799, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-29921691

RESUMO

Nonsteroidal anti-inflammatory drugs' (NSAID) use has consistently been associated with lower risk of colorectal cancer; however, studies showed inconsistent results on which cohort of individuals may benefit most. We performed multivariable logistic regression analysis to systematically test for the interaction between regular use of NSAIDs and other lifestyle and dietary factors on colorectal cancer risk among 11,894 cases and 15,999 controls. Fixed-effects meta-analyses were used for stratified analyses across studies for each risk factor and to summarize the estimates from interactions. Regular use of any NSAID, aspirin, or nonaspirin NSAIDs was significantly associated with a lower risk of colorectal cancer within almost all subgroups. However, smoking status and BMI were found to modify the NSAID-colorectal cancer association. Aspirin use was associated with a 29% lower colorectal cancer risk among never-smokers [odds ratios (OR) = 0.71; 95% confidence intervals (CI): 0.64-0.79], compared with 19% and 17% lower colorectal cancer risk among smokers of pack-years below median (OR, 0.81; 95% CI, 0.71-0.92) and above median (OR, 0.83; 95% CI, 0.74-0.94), respectively (P interaction = 0.048). The association between any NSAID use and colorectal cancer risk was also attenuated with increasing BMI (P interaction = 0.075). Collectively, these results suggest that obese individuals and heavy smokers are unlikely to benefit as much as other groups from the prophylactic effect of aspirin against colorectal cancer.Significance: Obesity and heavy smoking attenuate the benefit of aspirin use for colorectal cancer prevention. Cancer Res; 78(16); 4790-9. ©2018 AACR.

20.
Gastroenterology ; 155(4): 1059-1068.e2, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29935150

RESUMO

BACKGROUND & AIMS: Screening for colorectal cancer (CRC) with sigmoidoscopy reduces CRC incidence by detecting and removing adenomas. The number needed to screen is a measure of screening efficiency, but is not directly associated with adenoma removal. We propose the following 2 new metrics for quantifying the relationship between adenoma removal and CRC prevented: number of adenomas needed to remove (NNR) and adenoma dwell time avoided (DTA). METHODS: We collected data from 4 randomized trials of sigmoidoscopy screening (1 in the United States and 3 in Europe) to assess NNR and DTA. For each trial, NNR was computed as the number of adenomas removed from subjects in the intervention group, divided by the number of CRCs prevented. DTA was computed similarly but taking into account the timing of adenoma removal. Combined results across trials were assessed using standard meta-analytic techniques. RESULTS: The estimated NNR for the PLCO (Prostate, Lung, Colorectal and Ovarian) trial was 74 (95% confidence interval [CI], 56-110), for the NORCCAP (Norwegian Colorectal Cancer Prevention) trial was 71 (95% CI, 44-174), for the SCORE (Screening for Colon Rectum) trial was 27 (95% CI, 14-135), and for the UKFSST (UK Flexible Sigmoidoscopy Screening Trial) was 36 (95% CI, 28-52). The combined estimate (meta-analysis) of NNR was 52 (95% CI, 36-93) assuming heterogeneity (P for heterogeneity = .014). DTA estimates among trials ranged from 278 to 730 years, with a combined estimate of 500 (95% CI, 344-833) years assuming heterogeneity (P for heterogeneity = .035), or 2 CRC cases prevented per 1000 adenoma dwell years avoided. The combined estimates of NNR and DTA restricted to advanced adenomas were 13 (95% CI, 9-22) and 122 (95% CI, 90-190) years, respectively. CONCLUSIONS: We collected data from 4 randomized trials of sigmoidoscopy screening for CRC to develop metrics of endoscopic efficiency, NNR and DTA, which are directly linked to adenoma detection and removal. They can be used to compare screening among endoscopic modalities and to more precisely measure adenoma to carcinoma transition rates.


Assuntos
Adenoma/patologia , Adenoma/cirurgia , Transformação Celular Neoplásica/patologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Técnicas de Apoio para a Decisão , Detecção Precoce de Câncer/métodos , Sigmoidoscopia , Adenoma/epidemiologia , Idoso , Neoplasias Colorretais/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Números Necessários para Tratar , Valor Preditivo dos Testes , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia
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