26 results on '"Schoen, Robert E."'
Search Results
2. Comparative Effectiveness and Cost-Effectiveness of Colorectal Cancer Screening With Blood-Based Biomarkers (Liquid Biopsy) vs Fecal Tests or Colonoscopy.
- Author
-
Ladabaum U, Mannalithara A, Weng Y, Schoen RE, Dominitz JA, Desai M, and Lieberman D
- Subjects
- Humans, Liquid Biopsy economics, Biomarkers, Tumor blood, Biomarkers, Tumor analysis, Markov Chains, Quality-Adjusted Life Years, Middle Aged, Male, Female, Aged, Feces chemistry, United States, Incidence, Predictive Value of Tests, Comparative Effectiveness Research, Health Care Costs, Colorectal Neoplasms diagnosis, Colorectal Neoplasms economics, Cost-Benefit Analysis, Colonoscopy economics, Early Detection of Cancer economics, Early Detection of Cancer methods, Occult Blood
- Abstract
Background & Aims: Colorectal cancer (CRC) screening is highly effective but underused. Blood-based biomarkers (liquid biopsy) could improve screening participation., Methods: Using our established Markov model, screening every 3 years with a blood-based test that meets minimum Centers for Medicare & Medicaid Services' thresholds (CMS
min ) (CRC sensitivity 74%, specificity 90%) was compared with established alternatives. Test attributes were varied in sensitivity analyses., Results: CMSmin reduced CRC incidence by 40% and CRC mortality by 52% vs no screening. These reductions were less profound than the 68%-79% and 73%-81%, respectively, achieved with multi-target stool DNA (Cologuard; Exact Sciences) every 3 years, annual fecal immunochemical testing (FIT), or colonoscopy every 10 years. Assuming the same cost as multi-target stool DNA, CMSmin cost $28,500/quality-adjusted life-year gained vs no screening, but FIT, colonoscopy, and multi-target stool DNA were less costly and more effective. CMSmin would match FIT's clinical outcomes if it achieved 1.4- to 1.8-fold FIT's participation rate. Advanced precancerous lesion (APL) sensitivity was a key determinant of a test's effectiveness. A paradigm-changing blood-based test (sensitivity >90% for CRC and 80% for APL; 90% specificity; cost ≤$120-$140) would be cost-effective vs FIT at comparable participation., Conclusions: CMSmin could contribute to CRC control by achieving screening in those who will not use established methods. Substituting blood-based testing for established effective CRC screening methods will require higher CRC and APL sensitivities that deliver programmatic benefits matching those of FIT. High APL sensitivity, which can result in CRC prevention, should be a top priority for screening test developers. APL detection should not be penalized by a definition of test specificity that focuses on CRC only., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF
3. NordICC's 10-Year Interim Results Are Unexpected and Inconsistent With Modeling Predictions.
- Author
-
Ladabaum U, Schoen RE, and Meester R
- Published
- 2024
- Full Text
- View/download PDF
4. Reply.
- Author
-
Ladabaum U, Mannalithara A, Meester RGS, Gupta S, and Schoen RE
- Published
- 2023
- Full Text
- View/download PDF
5. Clinical and Genomic Characterization of Interval Colorectal Cancer in 3 Prospective Cohorts.
- Author
-
Yang K, Cao Y, Gurjao C, Liu Y, Guo CG, Lo CH, Zong X, Drew D, Geraghty C, Prezioso E, Moore M, Williams C, Riley T, Saul M, Ogino S, Giannakis M, Bass A, Schoen RE, and Chan AT
- Subjects
- Humans, Male, Follow-Up Studies, Prospective Studies, Colorectal Neoplasms diagnosis, Colorectal Neoplasms genetics, Genomics
- Abstract
Background & Aims: Interval colorectal cancers (CRCs), cancers diagnosed after a screening/surveillance examination in which no cancer is detected, and before the date of next recommended examination, reflect an unprecedented challenge in CRC detection and prevention. To better understand this poorly characterized CRC variant, we examined the clinical and mutational characteristics of interval CRCs in comparison with screen detected CRCs., Methods: We included 1175 CRCs documented in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial and 3661 CRCs in the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS). Multivariable Cox models were performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of death risk. Whole exome sequencing was conducted in 147 PLCO cases and 796 NHS/HPFS cases., Results: A total of 619 deaths (312 CRC-specific) and 2404 deaths (1904 CRC-specific) were confirmed during follow-up of PLCO and NHS/HPFS, respectively. Compared with screen detected CRCs, interval CRCs had a multivariate-adjusted HR (95% CI) of 1.47 (1.21-1.78) for CRC-specific mortality and 1.27 (1.09-1.47) for overall mortality (meta-analysis combining all 3 cohorts). However, we did not observe significant differences in mutational features between interval and screen detected CRCs (false discovery rate adjusted P > .05)., Conclusion: Interval CRCs had a significantly increased risk of death compared with screen detected CRCs that were not explained by established clinical prognostic factors, including stage at diagnosis. The survival disadvantage of interval CRCs did not appear to be explained by differences in the genomic landscape of tumors characterized by whole exome sequencing., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
6. Identifying Novel Susceptibility Genes for Colorectal Cancer Risk From a Transcriptome-Wide Association Study of 125,478 Subjects.
- Author
-
Guo X, Lin W, Wen W, Huyghe J, Bien S, Cai Q, Harrison T, Chen Z, Qu C, Bao J, Long J, Yuan Y, Wang F, Bai M, Abecasis GR, Albanes D, Berndt SI, Bézieau S, Bishop DT, Brenner H, Buch S, Burnett-Hartman A, Campbell PT, Castellví-Bel S, Chan AT, Chang-Claude J, Chanock SJ, Cho SH, Conti DV, Chapelle A, Feskens EJM, Gallinger SJ, Giles GG, Goodman PJ, Gsur A, Guinter M, Gunter MJ, Hampe J, Hampel H, Hayes RB, Hoffmeister M, Kampman E, Kang HM, Keku TO, Kim HR, Le Marchand L, Lee SC, Li CI, Li L, Lindblom A, Lindor N, Milne RL, Moreno V, Murphy N, Newcomb PA, Nickerson DA, Offit K, Pearlman R, Pharoah PDP, Platz EA, Potter JD, Rennert G, Sakoda LC, Schafmayer C, Schmit SL, Schoen RE, Schumacher FR, Slattery ML, Su YR, Tangen CM, Ulrich CM, van Duijnhoven FJB, Van Guelpen B, Visvanathan K, Vodicka P, Vodickova L, Vymetalkova V, Wang X, White E, Wolk A, Woods MO, Casey G, Hsu L, Jenkins MA, Gruber SB, Peters U, and Zheng W
- Subjects
- Alleles, Carcinogenesis genetics, Case-Control Studies, Cohort Studies, Colorectal Neoplasms epidemiology, Gene Knockdown Techniques, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Promoter Regions, Genetic genetics, RNA-Seq, Risk Factors, Xenograft Model Antitumor Assays, Biomarkers, Tumor genetics, Colorectal Neoplasms genetics, Genetic Predisposition to Disease, Models, Genetic
- Abstract
Background and Aims: Susceptibility genes and the underlying mechanisms for the majority of risk loci identified by genome-wide association studies (GWAS) for colorectal cancer (CRC) risk remain largely unknown. We conducted a transcriptome-wide association study (TWAS) to identify putative susceptibility genes., Methods: Gene-expression prediction models were built using transcriptome and genetic data from the 284 normal transverse colon tissues of European descendants from the Genotype-Tissue Expression (GTEx), and model performance was evaluated using data from The Cancer Genome Atlas (n = 355). We applied the gene-expression prediction models and GWAS data to evaluate associations of genetically predicted gene-expression with CRC risk in 58,131 CRC cases and 67,347 controls of European ancestry. Dual-luciferase reporter assays and knockdown experiments in CRC cells and tumor xenografts were conducted., Results: We identified 25 genes associated with CRC risk at a Bonferroni-corrected threshold of P < 9.1 × 10
-6 , including genes in 4 novel loci, PYGL (14q22.1), RPL28 (19q13.42), CAPN12 (19q13.2), MYH7B (20q11.22), and MAP1L3CA (20q11.22). In 9 known GWAS-identified loci, we uncovered 9 genes that have not been reported previously, whereas 4 genes remained statistically significant after adjusting for the lead risk variant of the locus. Through colocalization analysis in GWAS loci, we additionally identified 12 putative susceptibility genes that were supported by TWAS analysis at P < .01. We showed that risk allele of the lead risk variant rs1741640 affected the promoter activity of CABLES2. Knockdown experiments confirmed that CABLES2 plays a vital role in colorectal carcinogenesis., Conclusions: Our study reveals new putative susceptibility genes and provides new insight into the biological mechanisms underlying CRC development., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)- Published
- 2021
- Full Text
- View/download PDF
7. Screening For Colorectal Cancer in the Age of Simulation Models: A Historical Lens.
- Author
-
Phillips CJ and Schoen RE
- Subjects
- Clinical Decision-Making, Colorectal Neoplasms epidemiology, Colorectal Neoplasms history, Colorectal Neoplasms therapy, Evidence-Based Medicine, History, 20th Century, History, 21st Century, Humans, Predictive Value of Tests, Prognosis, Risk Assessment, Risk Factors, Colorectal Neoplasms diagnosis, Computer Simulation, Decision Support Techniques, Early Detection of Cancer history, Models, Theoretical
- Published
- 2020
- Full Text
- View/download PDF
8. Circulating Levels of Insulin-like Growth Factor 1 and Insulin-like Growth Factor Binding Protein 3 Associate With Risk of Colorectal Cancer Based on Serologic and Mendelian Randomization Analyses.
- Author
-
Murphy N, Carreras-Torres R, Song M, Chan AT, Martin RM, Papadimitriou N, Dimou N, Tsilidis KK, Banbury B, Bradbury KE, Besevic J, Rinaldi S, Riboli E, Cross AJ, Travis RC, Agnoli C, Albanes D, Berndt SI, Bézieau S, Bishop DT, Brenner H, Buchanan DD, Onland-Moret NC, Burnett-Hartman A, Campbell PT, Casey G, Castellví-Bel S, Chang-Claude J, Chirlaque MD, de la Chapelle A, English D, Figueiredo JC, Gallinger SJ, Giles GG, Gruber SB, Gsur A, Hampe J, Hampel H, Harrison TA, Hoffmeister M, Hsu L, Huang WY, Huyghe JR, Jenkins MA, Keku TO, Kühn T, Kweon SS, Le Marchand L, Li CI, Li L, Lindblom A, Martín V, Milne RL, Moreno V, Newcomb PA, Offit K, Ogino S, Ose J, Perduca V, Phipps AI, Platz EA, Potter JD, Qu C, Rennert G, Sakoda LC, Schafmayer C, Schoen RE, Slattery ML, Tangen CM, Ulrich CM, van Duijnhoven FJB, Van Guelpen B, Visvanathan K, Vodicka P, Vodickova L, Vymetalkova V, Wang H, White E, Wolk A, Woods MO, Wu AH, Zheng W, Peters U, and Gunter MJ
- Subjects
- Aged, Biomarkers, Tumor genetics, Case-Control Studies, Colorectal Neoplasms blood, Colorectal Neoplasms genetics, Female, Follow-Up Studies, Humans, Incidence, Insulin-Like Growth Factor Binding Protein 3 genetics, Insulin-Like Growth Factor I genetics, Insulin-Like Growth Factor II analysis, Male, Mendelian Randomization Analysis, Middle Aged, Polymorphism, Single Nucleotide, Registries statistics & numerical data, Risk Assessment methods, Risk Factors, Sex Factors, United Kingdom epidemiology, Biomarkers, Tumor blood, Colorectal Neoplasms epidemiology, Insulin-Like Growth Factor Binding Protein 3 blood, Insulin-Like Growth Factor I analysis
- Abstract
Background & Aims: Human studies examining associations between circulating levels of insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) and colorectal cancer risk have reported inconsistent results. We conducted complementary serologic and Mendelian randomization (MR) analyses to determine whether alterations in circulating levels of IGF1 or IGFBP3 are associated with colorectal cancer development., Methods: Serum levels of IGF1 were measured in blood samples collected from 397,380 participants from the UK Biobank, from 2006 through 2010. Incident cancer cases and cancer cases recorded first in death certificates were identified through linkage to national cancer and death registries. Complete follow-up was available through March 31, 2016. For the MR analyses, we identified genetic variants associated with circulating levels of IGF1 and IGFBP3. The association of these genetic variants with colorectal cancer was examined with 2-sample MR methods using genome-wide association study consortia data (52,865 cases with colorectal cancer and 46,287 individuals without [controls]) RESULTS: After a median follow-up period of 7.1 years, 2665 cases of colorectal cancer were recorded. In a multivariable-adjusted model, circulating level of IGF1 associated with colorectal cancer risk (hazard ratio per 1 standard deviation increment of IGF1, 1.11; 95% confidence interval [CI] 1.05-1.17). Similar associations were found by sex, follow-up time, and tumor subsite. In the MR analyses, a 1 standard deviation increment in IGF1 level, predicted based on genetic factors, was associated with a higher risk of colorectal cancer risk (odds ratio 1.08; 95% CI 1.03-1.12; P = 3.3 × 10
-4 ). Level of IGFBP3, predicted based on genetic factors, was associated with colorectal cancer risk (odds ratio per 1 standard deviation increment, 1.12; 95% CI 1.06-1.18; P = 4.2 × 10-5 ). Colorectal cancer risk was associated with only 1 variant in the IGFBP3 gene region (rs11977526), which also associated with anthropometric traits and circulating level of IGF2., Conclusions: In an analysis of blood samples from almost 400,000 participants in the UK Biobank, we found an association between circulating level of IGF1 and colorectal cancer. Using genetic data from 52,865 cases with colorectal cancer and 46,287 controls, a higher level of IGF1, determined by genetic factors, was associated with colorectal cancer. Further studies are needed to determine how this signaling pathway might contribute to colorectal carcinogenesis., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)- Published
- 2020
- Full Text
- View/download PDF
9. Cumulative Burden of Colorectal Cancer-Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer.
- Author
-
Archambault AN, Su YR, Jeon J, Thomas M, Lin Y, Conti DV, Win AK, Sakoda LC, Lansdorp-Vogelaar I, Peterse EFP, Zauber AG, Duggan D, Holowatyj AN, Huyghe JR, Brenner H, Cotterchio M, Bézieau S, Schmit SL, Edlund CK, Southey MC, MacInnis RJ, Campbell PT, Chang-Claude J, Slattery ML, Chan AT, Joshi AD, Song M, Cao Y, Woods MO, White E, Weinstein SJ, Ulrich CM, Hoffmeister M, Bien SA, Harrison TA, Hampe J, Li CI, Schafmayer C, Offit K, Pharoah PD, Moreno V, Lindblom A, Wolk A, Wu AH, Li L, Gunter MJ, Gsur A, Keku TO, Pearlman R, Bishop DT, Castellví-Bel S, Moreira L, Vodicka P, Kampman E, Giles GG, Albanes D, Baron JA, Berndt SI, Brezina S, Buch S, Buchanan DD, Trichopoulou A, Severi G, Chirlaque MD, Sánchez MJ, Palli D, Kühn T, Murphy N, Cross AJ, Burnett-Hartman AN, Chanock SJ, de la Chapelle A, Easton DF, Elliott F, English DR, Feskens EJM, FitzGerald LM, Goodman PJ, Hopper JL, Hudson TJ, Hunter DJ, Jacobs EJ, Joshu CE, Küry S, Markowitz SD, Milne RL, Platz EA, Rennert G, Rennert HS, Schumacher FR, Sandler RS, Seminara D, Tangen CM, Thibodeau SN, Toland AE, van Duijnhoven FJB, Visvanathan K, Vodickova L, Potter JD, Männistö S, Weigl K, Figueiredo J, Martín V, Larsson SC, Parfrey PS, Huang WY, Lenz HJ, Castelao JE, Gago-Dominguez M, Muñoz-Garzón V, Mancao C, Haiman CA, Wilkens LR, Siegel E, Barry E, Younghusband B, Van Guelpen B, Harlid S, Zeleniuch-Jacquotte A, Liang PS, Du M, Casey G, Lindor NM, Le Marchand L, Gallinger SJ, Jenkins MA, Newcomb PA, Gruber SB, Schoen RE, Hampel H, Corley DA, Hsu L, Peters U, and Hayes RB
- Subjects
- Age of Onset, Case-Control Studies, Cohort Studies, DNA Mutational Analysis, Datasets as Topic, Female, Genome-Wide Association Study, Genotyping Techniques, Humans, Life Style, Male, Medical History Taking, Middle Aged, Mutation Rate, Polymorphism, Single Nucleotide, Risk Factors, Whole Genome Sequencing, Colorectal Neoplasms genetics, Genetic Predisposition to Disease
- Abstract
Background & Aims: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC., Methods: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants., Results: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 × 10
-5 ). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings., Conclusions: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)- Published
- 2020
- Full Text
- View/download PDF
10. Strategies for Colorectal Cancer Screening.
- Author
-
Ladabaum U, Dominitz JA, Kahi C, and Schoen RE
- Subjects
- Colonoscopy standards, Colonoscopy statistics & numerical data, Colorectal Neoplasms epidemiology, Colorectal Neoplasms prevention & control, Early Detection of Cancer statistics & numerical data, Healthy Lifestyle, Humans, Incidence, Mass Screening organization & administration, Mass Screening statistics & numerical data, Occult Blood, Patient Acceptance of Health Care statistics & numerical data, Practice Guidelines as Topic, Risk Assessment standards, Sigmoidoscopy standards, Sigmoidoscopy statistics & numerical data, Colorectal Neoplasms diagnosis, Early Detection of Cancer standards, Global Burden of Disease, Health Plan Implementation standards, Mass Screening standards
- Abstract
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 people 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., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
11. Cost-Effectiveness and National Effects of Initiating Colorectal Cancer Screening for Average-Risk Persons at Age 45 Years Instead of 50 Years.
- Author
-
Ladabaum U, Mannalithara A, Meester RGS, Gupta S, and Schoen RE
- Subjects
- Age Factors, Aged, American Cancer Society, Colonoscopy economics, Cost-Benefit Analysis, Decision Support Techniques, Early Detection of Cancer economics, Female, Humans, Immunochemistry economics, Immunochemistry methods, Male, Markov Chains, Middle Aged, Practice Guidelines as Topic, Quality-Adjusted Life Years, United States, Colonoscopy methods, Colorectal Neoplasms diagnosis, Early Detection of Cancer methods, Occult Blood
- Abstract
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., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
12. Number of Adenomas Removed and Colorectal Cancers Prevented in Randomized Trials of Flexible Sigmoidoscopy Screening.
- Author
-
Pinsky PF, Loberg M, Senore C, Wooldrage K, Atkin W, Bretthauer M, Cross AJ, Hoff G, Holme O, Kalager M, Segnan N, and Schoen RE
- Subjects
- Adenoma epidemiology, Aged, Colorectal Neoplasms epidemiology, Europe epidemiology, Female, Humans, Incidence, Male, Middle Aged, Numbers Needed To Treat, Predictive Value of Tests, Prognosis, Randomized Controlled Trials as Topic, Risk Factors, Time Factors, United States epidemiology, Adenoma pathology, Adenoma surgery, Cell Transformation, Neoplastic pathology, Colorectal Neoplasms pathology, Colorectal Neoplasms surgery, Decision Support Techniques, Early Detection of Cancer methods, Sigmoidoscopy
- Abstract
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., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
13. Potential Intended and Unintended Consequences of Recommending Initiation of Colorectal Cancer Screening at Age 45 Years.
- Author
-
Liang PS, Allison J, Ladabaum U, Martinez ME, Murphy CC, Schoen RE, Shaukat A, Tinmouth J, and Gupta S
- Subjects
- Age Factors, Aged, Clinical Decision-Making, Colorectal Neoplasms ethnology, Colorectal Neoplasms mortality, Colorectal Neoplasms therapy, Early Detection of Cancer economics, Evidence-Based Medicine standards, Gastroenterology economics, Health Care Costs, Humans, Incidence, Middle Aged, Predictive Value of Tests, Prognosis, Risk Assessment, Risk Factors, United States epidemiology, Colorectal Neoplasms diagnosis, Early Detection of Cancer standards, Gastroenterology standards, Practice Guidelines as Topic standards
- Published
- 2018
- Full Text
- View/download PDF
14. World Endoscopy Organization Consensus Statements on Post-Colonoscopy and Post-Imaging Colorectal Cancer.
- Author
-
Rutter MD, Beintaris I, Valori R, Chiu HM, Corley DA, Cuatrecasas M, Dekker E, Forsberg A, Gore-Booth J, Haug U, Kaminski MF, Matsuda T, Meijer GA, Morris E, Plumb AA, Rabeneck L, Robertson DJ, Schoen RE, Singh H, Tinmouth J, Young GP, and Sanduleanu S
- Subjects
- Colon diagnostic imaging, Colonoscopy methods, Consensus, Early Detection of Cancer methods, Humans, Risk Factors, Time Factors, Colonoscopy standards, Colorectal Neoplasms diagnosis, Early Detection of Cancer standards, Practice Guidelines as Topic standards
- Abstract
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., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
15. Determining Risk of Colorectal Cancer and Starting Age of Screening Based on Lifestyle, Environmental, and Genetic Factors.
- Author
-
Jeon J, Du M, Schoen RE, Hoffmeister M, Newcomb PA, Berndt SI, Caan B, Campbell PT, Chan AT, Chang-Claude J, Giles GG, Gong J, Harrison TA, Huyghe JR, Jacobs EJ, Li L, Lin Y, Le Marchand L, Potter JD, Qu C, Bien SA, Zubair N, Macinnis RJ, Buchanan DD, Hopper JL, Cao Y, Nishihara R, Rennert G, Slattery ML, Thomas DC, Woods MO, Prentice RL, Gruber SB, Zheng Y, Brenner H, Hayes RB, White E, Peters U, and Hsu L
- Subjects
- Age Factors, Aged, Colorectal Neoplasms genetics, Early Detection of Cancer methods, Environment, Female, Humans, Life Style, Male, Middle Aged, Polymorphism, Single Nucleotide, Practice Guidelines as Topic, ROC Curve, Risk Assessment methods, Sex Factors, Colonoscopy standards, Colorectal Neoplasms diagnosis, Early Detection of Cancer standards, Models, Biological
- Abstract
Background & Aims: Guidelines for initiating colorectal cancer (CRC) screening are based on family history but do not consider lifestyle, environmental, or genetic risk factors. We developed models to determine risk of CRC, based on lifestyle and environmental factors and genetic variants, and to identify an optimal age to begin screening., Methods: We collected data from 9748 CRC cases and 10,590 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colorectal Transdisciplinary study, from 1992 through 2005. Half of the participants were used to develop the risk determination model and the other half were used to evaluate the discriminatory accuracy (validation set). Models of CRC risk were created based on family history, 19 lifestyle and environmental factors (E-score), and 63 CRC-associated single-nucleotide polymorphisms identified in genome-wide association studies (G-score). We evaluated the discriminatory accuracy of the models by calculating area under the receiver operating characteristic curve values, adjusting for study, age, and endoscopy history for the validation set. We used the models to project the 10-year absolute risk of CRC for a given risk profile and recommend ages to begin screening in comparison to CRC risk for an average individual at 50 years of age, using external population incidence rates for non-Hispanic whites from the Surveillance, Epidemiology, and End Results program registry., Results: In our models, E-score and G-score each determined risk of CRC with greater accuracy than family history. A model that combined both scores and family history estimated CRC risk with an area under the receiver operating characteristic curve value of 0.63 (95% confidence interval, 0.62-0.64) for men and 0.62 (95% confidence interval, 0.61-0.63) for women; area under the receiver operating characteristic curve values based on only family history ranged from 0.53 to 0.54 and those based only E-score or G-score ranged from 0.59 to 0.60. Although screening is recommended to begin at age 50 years for individuals with no family history of CRC, starting ages calculated based on combined E-score and G-score differed by 12 years for men and 14 for women, for individuals with the highest vs the lowest 10% of risk., Conclusions: We used data from 2 large international consortia to develop CRC risk calculation models that included genetic and environmental factors along with family history. These determine risk of CRC and starting ages for screening with greater accuracy than the family history only model, which is based on the current screening guideline. These scoring systems might serve as a first step toward developing individualized CRC prevention strategies., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
16. Identification of Susceptibility Loci and Genes for Colorectal Cancer Risk.
- Author
-
Zeng C, Matsuda K, Jia WH, Chang J, Kweon SS, Xiang YB, Shin A, Jee SH, Kim DH, Zhang B, Cai Q, Guo X, Long J, Wang N, Courtney R, Pan ZZ, Wu C, Takahashi A, Shin MH, Matsuo K, Matsuda F, Gao YT, Oh JH, Kim S, Jung KJ, Ahn YO, Ren Z, Li HL, Wu J, Shi J, Wen W, Yang G, Li B, Ji BT, Brenner H, Schoen RE, Küry S, Gruber SB, Schumacher FR, Stenzel SL, Casey G, Hopper JL, Jenkins MA, Kim HR, Jeong JY, Park JW, Tajima K, Cho SH, Kubo M, Shu XO, Lin D, Zeng YX, and Zheng W
- Subjects
- Adult, Aged, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors genetics, Case-Control Studies, Eukaryotic Initiation Factor-3 genetics, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Qb-SNARE Proteins genetics, Ribosomal Proteins genetics, Risk Factors, Steroid 17-alpha-Hydroxylase genetics, Suppressor of Cytokine Signaling Proteins genetics, Young Adult, Asian People genetics, Colorectal Neoplasms genetics, Genetic Loci, Genetic Predisposition to Disease
- Abstract
Background & Aims: Known genetic factors explain only a small fraction of genetic variation in colorectal cancer (CRC). We conducted a genome-wide association study to identify risk loci for CRC., Methods: This discovery stage included 8027 cases and 22,577 controls of East-Asian ancestry. Promising variants were evaluated in studies including as many as 11,044 cases and 12,047 controls. Tumor-adjacent normal tissues from 188 patients were analyzed to evaluate correlations of risk variants with expression levels of nearby genes. Potential functionality of risk variants were evaluated using public genomic and epigenomic databases., Results: We identified 4 loci associated with CRC risk; P values for the most significant variant in each locus ranged from 3.92 × 10(-8) to 1.24 × 10(-12): 6p21.1 (rs4711689), 8q23.3 (rs2450115, rs6469656), 10q24.3 (rs4919687), and 12p13.3 (rs11064437). We also identified 2 risk variants at loci previously associated with CRC: 10q25.2 (rs10506868) and 20q13.3 (rs6061231). These risk variants, conferring an approximate 10%-18% increase in risk per allele, are located either inside or near protein-coding genes that include transcription factor EB (lysosome biogenesis and autophagy), eukaryotic translation initiation factor 3, subunit H (initiation of translation), cytochrome P450, family 17, subfamily A, polypeptide 1 (steroidogenesis), splA/ryanodine receptor domain and SOCS box containing 2 (proteasome degradation), and ribosomal protein S2 (ribosome biogenesis). Gene expression analyses showed a significant association (P < .05) for rs4711689 with transcription factor EB, rs6469656 with eukaryotic translation initiation factor 3, subunit H, rs11064437 with splA/ryanodine receptor domain and SOCS box containing 2, and rs6061231 with ribosomal protein S2., Conclusions: We identified susceptibility loci and genes associated with CRC risk, linking CRC predisposition to steroid hormone, protein synthesis and degradation, and autophagy pathways and providing added insight into the mechanism of CRC pathogenesis., (Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
17. Post-Polypectomy Surveillance That Would Please Goldilocks--Not Too Much, Not Too Little, but Just Right.
- Author
-
Ladabaum U and Schoen RE
- Subjects
- Adenomatous Polyps pathology, Clinical Protocols, Colonic Polyps pathology, Colorectal Neoplasms pathology, Humans, Practice Guidelines as Topic, Predictive Value of Tests, Randomized Controlled Trials as Topic, Research Design, Time Factors, Treatment Outcome, Adenomatous Polyps surgery, Colectomy adverse effects, Colonic Polyps surgery, Colonoscopy standards, Colorectal Neoplasms surgery
- Published
- 2016
- Full Text
- View/download PDF
18. Incidence and mortality of colorectal cancer in individuals with a family history of colorectal cancer.
- Author
-
Schoen RE, Razzak A, Yu KJ, Berndt SI, Firl K, Riley TL, and Pinsky PF
- Subjects
- Age Factors, Aged, Colorectal Neoplasms epidemiology, Early Detection of Cancer statistics & numerical data, Female, Follow-Up Studies, Humans, Incidence, Male, Mass Screening methods, Middle Aged, Risk Factors, Colonoscopy, Colorectal Neoplasms diagnosis, Colorectal Neoplasms mortality, Early Detection of Cancer methods, Family, Sigmoidoscopy
- Abstract
Background & Aims: Little is known about the change in risk conferred by family history of colorectal cancer (CRC) as a person ages. We evaluated the effect of family history on CRC incidence and mortality after 55 years of age, when the risk of early onset cancer had passed., Methods: We collected data from participants in the randomized, controlled Prostate, Lung, Colorectal and Ovarian cancer screening trial of flexible sigmoidoscopy versus usual care (55-74 years old, no history of CRC), performed at 10 US centers from 1993 to 2001. A detailed family history of colorectal cancer was obtained at enrollment, and subjects were followed for CRC incidence and mortality for up to 13 years., Results: Among 144,768 participants, 14,961 subjects (10.3%) reported a family of CRC. Of 2090 incident cases, 273 cases (13.1%) had a family history of CRC; among 538 deaths from CRC, 71 (13.2%) had a family history of CRC. Overall, family history of CRC was associated with an increased risk of CRC incidence (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.10-1.50; P<.0001) and increased mortality (HR, 1.31; 95% CI, 1.02-1.69; P = .03). Subjects with 1 first degree relative (FDR) with CRC (n = 238; HR, 1.23; 95% CI, 1.07-1.42) or ≥2 FDRs with CRC (n = 35; HR, 2.04; 95% CI, 1.44-2.86) were at increased risk for incident CRC. However, among individuals with 1 FDR with CRC, there were no differences in risk based on age at diagnosis in the FDR (for FDR <60 years of age: HR, 1.27; 95% CI, 0.97-1.63; for FDR 60-70 years of age: HR, 1.33; 95% CI, 1.06-1.62; for FDR >70 years of age: HR, 1.14; 95% CI, 0.93-1.45; P trend = .59)., Conclusions: After 55 years of age, subjects with 1 FDR with CRC had only a modest increase in risk for CRC incidence and death; age of onset in the FDR was not significantly associated with risk. Individuals with ≥2 FDRs with CRC had continued increased risk in older age. Guidelines and clinical practice for subjects with a family history of CRC should be modified to align CRC testing to risk. ClinicalTrials.gov number, NCT00002540., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
19. A model to determine colorectal cancer risk using common genetic susceptibility loci.
- Author
-
Hsu L, Jeon J, Brenner H, Gruber SB, Schoen RE, Berndt SI, Chan AT, Chang-Claude J, Du M, Gong J, Harrison TA, Hayes RB, Hoffmeister M, Hutter CM, Lin Y, Nishihara R, Ogino S, Prentice RL, Schumacher FR, Seminara D, Slattery ML, Thomas DC, Thornquist M, Newcomb PA, Potter JD, Zheng Y, White E, and Peters U
- Subjects
- Age Factors, Case-Control Studies, Colonoscopy, Colorectal Neoplasms pathology, Decision Support Techniques, Female, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Germany, Humans, Logistic Models, Male, Middle Aged, Odds Ratio, Pedigree, Phenotype, Prognosis, Reproducibility of Results, Risk Assessment, Risk Factors, Sex Factors, United States, Biomarkers, Tumor genetics, Colorectal Neoplasms genetics, Genetic Loci, Models, Genetic, Models, Statistical, Polymorphism, Single Nucleotide
- Abstract
Background & Aims: Risk for colorectal cancer (CRC) can be greatly reduced through screening. To aid in the development of screening strategies, we refined models designed to determine risk of CRC by incorporating information from common genetic susceptibility loci., Methods: By using data collected from more than 12,000 participants in 6 studies performed from 1990 through 2011 in the United States and Germany, we developed risk determination models based on sex, age, family history, genetic risk score (number of risk alleles carried at 27 validated common CRC susceptibility loci), and history of endoscopic examinations. The model was validated using data collected from approximately 1800 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, conducted from 1993 through 2001 in the United States., Results: We identified a CRC genetic risk score that independently predicted which patients in the training set would develop CRC. Compared with determination of risk based only on family history, adding the genetic risk score increased the discriminatory accuracy from 0.51 to 0.59 (P = .0028) for men and from 0.52 to 0.56 (P = .14) for women. We calculated age- and sex-specific 10-year CRC absolute risk estimates based on the number of risk alleles, family history, and history of endoscopic examinations. A model that included a genetic risk score better determined the recommended starting age for screening in subjects with and without family histories of CRC. The starting age for high-risk men (family history of CRC and genetic risk score, 90%) was 42 years, and for low-risk men (no family history of CRC and genetic risk score, 10%) was 52 years. For men with no family history and a high genetic risk score (90%), the starting age would be 47 years; this is an intermediate value that is 5 years earlier than it would be for men with a genetic risk score of 10%. Similar trends were observed in women., Conclusions: By incorporating information on CRC risk alleles, we created a model to determine the risk for CRC more accurately. This model might be used to develop screening and prevention strategies., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
20. Mesalamine did not prevent recurrent diverticulitis in phase 3 controlled trials.
- Author
-
Raskin JB, Kamm MA, Jamal MM, Márquez J, Melzer E, Schoen RE, Szalóki T, Barrett K, and Streck P
- Subjects
- Adult, Aged, Anti-Inflammatory Agents adverse effects, Colectomy, Colonic Diseases diagnosis, Colonic Diseases surgery, Diverticulitis diagnosis, Diverticulitis surgery, Female, Gastrointestinal Agents adverse effects, Humans, Male, Middle Aged, Secondary Prevention, Time Factors, Treatment Outcome, United States, Anti-Inflammatory Agents therapeutic use, Colonic Diseases drug therapy, Diverticulitis drug therapy, Gastrointestinal Agents therapeutic use, Mesalamine therapeutic use
- Abstract
Background & Aims: No therapy has been proven to prevent the recurrence of diverticulitis. Mesalamine has shown efficacy in preventing relapse in inflammatory bowel disease, and there is preliminary evidence that it might be effective for diverticular disease. We investigated the efficacy of mesalamine in preventing recurrence of diverticulitis in 2 identical but separate phase 3, randomized, double-blind, placebo-controlled, multicenter trials (identical confirmatory trials were conducted for regulatory reasons)., Methods: We evaluated the efficacy and safety of multimatrix mesalamine vs placebo in the prevention of recurrent diverticulitis in 590 (PREVENT1) and 592 (PREVENT2) adult patients with ≥1 episodes of acute diverticulitis in the previous 24 months that resolved without surgery. Patients received mesalamine (1.2 g, 2.4 g, or 4.8 g) or placebo once daily for 104 weeks. The primary end point was the proportion of recurrence-free patients at week 104. Diverticulitis recurrence was defined as surgical intervention at any time for diverticular disease or presence of computed tomography scan results demonstrating bowel wall thickening (>5 mm) and/or fat stranding consistent with diverticulitis. For a portion of the study, recurrence also required the presence of abdominal pain and an increase in white blood cells., Results: Mesalamine did not reduce the rate of diverticulitis recurrence at week 104. Among patients in PREVENT1, 53%-63% did not have disease recurrence, compared with 65% of those given placebo. Among patients in PREVENT2, 59%-69% of patients did not have disease recurrence, compared with 68% of those given placebo. Mesalamine did not reduce time to recurrence, and the proportions of patients requiring surgery were comparable among treatment groups. No new adverse events were identified with mesalamine administration., Conclusions: Mesalamine was not superior to placebo in preventing recurrent diverticulitis. Mesalamine is not recommended for this indication. ClinicalTrials.gov ID: NCT00545740 and NCT00545103., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
21. Can symptomatic cancer be distinguished from screen detected cancer?
- Author
-
Schoen RE and Pinsky PF
- Subjects
- Female, Humans, Male, Adenoma pathology, Colonic Polyps pathology, Colonoscopy, Colorectal Neoplasms pathology
- Published
- 2014
- Full Text
- View/download PDF
22. Peripancreatic enhancing lesion in a cirrhotic patient.
- Author
-
Luo J, Malik SM, and Schoen RE
- Subjects
- Aged, Aneurysm etiology, Humans, Hypertension, Portal complications, Liver Cirrhosis, Alcoholic complications, Male, Tomography, X-Ray Computed, Venous Thrombosis etiology, Aneurysm diagnostic imaging, Hypertension, Portal diagnostic imaging, Liver Cirrhosis, Alcoholic diagnostic imaging, Portal Vein diagnostic imaging, Venous Thrombosis diagnostic imaging
- Published
- 2014
- Full Text
- View/download PDF
23. Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-analysis.
- Author
-
Peters U, Jiao S, Schumacher FR, Hutter CM, Aragaki AK, Baron JA, Berndt SI, Bézieau S, Brenner H, Butterbach K, Caan BJ, Campbell PT, Carlson CS, Casey G, Chan AT, Chang-Claude J, Chanock SJ, Chen LS, Coetzee GA, Coetzee SG, Conti DV, Curtis KR, Duggan D, Edwards T, Fuchs CS, Gallinger S, Giovannucci EL, Gogarten SM, Gruber SB, Haile RW, Harrison TA, Hayes RB, Henderson BE, Hoffmeister M, Hopper JL, Hudson TJ, Hunter DJ, Jackson RD, Jee SH, Jenkins MA, Jia WH, Kolonel LN, Kooperberg C, Küry S, Lacroix AZ, Laurie CC, Laurie CA, Le Marchand L, Lemire M, Levine D, Lindor NM, Liu Y, Ma J, Makar KW, Matsuo K, Newcomb PA, Potter JD, Prentice RL, Qu C, Rohan T, Rosse SA, Schoen RE, Seminara D, Shrubsole M, Shu XO, Slattery ML, Taverna D, Thibodeau SN, Ulrich CM, White E, Xiang Y, Zanke BW, Zeng YX, Zhang B, Zheng W, and Hsu L
- Subjects
- Age Distribution, Aged, Aged, 80 and over, Colorectal Neoplasms epidemiology, DNA-Binding Proteins genetics, Female, Genome-Wide Association Study, Humans, Incidence, Laminin genetics, Male, Middle Aged, Polymorphism, Single Nucleotide, Prognosis, Risk Assessment, Sex Distribution, T-Box Domain Proteins genetics, Colorectal Neoplasms genetics, Cyclin D2 genetics, Genetic Loci genetics, Genetic Predisposition to Disease epidemiology
- Abstract
Background & Aims: Heritable factors contribute to the development of colorectal cancer. Identifying the genetic loci associated with colorectal tumor formation could elucidate the mechanisms of pathogenesis., Methods: We conducted a genome-wide association study that included 14 studies, 12,696 cases of colorectal tumors (11,870 cancer, 826 adenoma), and 15,113 controls of European descent. The 10 most statistically significant, previously unreported findings were followed up in 6 studies; these included 3056 colorectal tumor cases (2098 cancer, 958 adenoma) and 6658 controls of European and Asian descent., Results: Based on the combined analysis, we identified a locus that reached the conventional genome-wide significance level at less than 5.0 × 10(-8): an intergenic region on chromosome 2q32.3, close to nucleic acid binding protein 1 (most significant single nucleotide polymorphism: rs11903757; odds ratio [OR], 1.15 per risk allele; P = 3.7 × 10(-8)). We also found evidence for 3 additional loci with P values less than 5.0 × 10(-7): a locus within the laminin gamma 1 gene on chromosome 1q25.3 (rs10911251; OR, 1.10 per risk allele; P = 9.5 × 10(-8)), a locus within the cyclin D2 gene on chromosome 12p13.32 (rs3217810 per risk allele; OR, 0.84; P = 5.9 × 10(-8)), and a locus in the T-box 3 gene on chromosome 12q24.21 (rs59336; OR, 0.91 per risk allele; P = 3.7 × 10(-7))., Conclusions: In a large genome-wide association study, we associated polymorphisms close to nucleic acid binding protein 1 (which encodes a DNA-binding protein involved in DNA repair) with colorectal tumor risk. We also provided evidence for an association between colorectal tumor risk and polymorphisms in laminin gamma 1 (this is the second gene in the laminin family to be associated with colorectal cancers), cyclin D2 (which encodes for cyclin D2), and T-box 3 (which encodes a T-box transcription factor and is a target of Wnt signaling to β-catenin). The roles of these genes and their products in cancer pathogenesis warrant further investigation., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
24. Utilization of surveillance colonoscopy in community practice.
- Author
-
Schoen RE, Pinsky PF, Weissfeld JL, Yokochi LA, Reding DJ, Hayes RB, Church T, Yurgalevich S, Doria-Rose VP, Hickey T, Riley T, and Berg CD
- Subjects
- Adenoma diagnosis, Adenomatous Polyps diagnosis, Aged, Colonic Neoplasms diagnosis, Female, Follow-Up Studies, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Population Surveillance, Retrospective Studies, Risk Factors, United States epidemiology, Adenoma epidemiology, Adenomatous Polyps epidemiology, Colonic Neoplasms epidemiology, Colonoscopy statistics & numerical data, Community Health Services statistics & numerical data, Gastroenterology statistics & numerical data
- Abstract
Background & Aims: The recommended timing of surveillance colonoscopy for individuals with adenomatous polyps is based on adenoma histology, size, and number. The burden and cost of surveillance colonoscopy are significant. The aim of this study was to examine the use of surveillance colonoscopy on a community-wide basis., Methods: We retrospectively queried participants in the Prostate, Lung, Colorectal, and Ovarian Cancer screening trial in 9 US communities about use of surveillance colonoscopy. Subjects whose initial colonoscopy showed advanced adenoma (AA), nonadvanced adenoma (NAA), or no adenoma (NA) findings were included. Colonoscopy examinations were confirmed by reviewing colonoscopy reports., Results: Of 3876 subjects selected for inquiry, 3627 (93.6%) responded. The cumulative probability of a surveillance colonoscopy within 5 years was 58.4% (n = 1342) in the AA group, 57.5% in those with >or=3 NAAs (n = 117), 46.7% in those with 1-2 NAAs (n = 905), and 26.5% (n = 1263) in subjects with NAs. Within 7 years, 33.2% of subjects with AAs received >or=2 surveillance examinations versus 26.9% for those with >or=3 NAAs, 18.2% for those with 1 or 2 NAAs, and 10.4% for those with NAs. Incomplete colonoscopy, family history of colorectal cancer, or interval adenomatous findings could explain only a minority of surveillance colonoscopy in low-risk subjects., Conclusions: In community practice, there is substantial overuse of surveillance colonoscopy among low-risk subjects and underuse among subjects with AAs. Interventions to better align use of surveillance colonoscopy with risk for advanced lesions are needed., (Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
25. Yield of advanced adenoma and cancer based on polyp size detected at screening flexible sigmoidoscopy.
- Author
-
Schoen RE, Weissfeld JL, Pinsky PF, and Riley T
- Subjects
- Aged, Disease Progression, Female, Humans, Male, Mass Screening methods, Middle Aged, Randomized Controlled Trials as Topic, Adenoma diagnosis, Adenoma pathology, Colonic Neoplasms diagnosis, Colonic Neoplasms pathology, Colonic Polyps pathology, Sigmoidoscopy methods
- Abstract
Background & Aims: Observational screening of the colon with subsequent referral for colonoscopy raises questions about the threshold of polyp size that necessitates referral. To examine the yield at colonoscopy when a given size lesion is observed, we assessed the yield of advanced adenoma and cancer at colonoscopy based on the size of the abnormality detected at flexible sigmoidoscopy (FSG)., Methods: We used data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a randomized, controlled, community-based study of FSG., Results: Subsequent colonoscopy was performed on 10,850 subjects (60.4% male; mean age, 62.9 years) with a polyp visualized on screening FSG. For women with a polyp 0.5-0.9 cm on FSG (n = 1426), the yield in the distal colon on colonoscopy was 0.6% for cancer (number needed to screen [NNS] = 166) and 14.5% for advanced adenoma (NNS = 7). In men (n = 2183), the yield was 0.7% (NNS = 142) for cancer and 15.9% (NNS = 6) for advanced adenoma. Among persons with polyps 0.5-0.9 cm identified on FSG, 5.5% (198/3609) had distal advanced adenomas that measured <1.0 cm but had villous histology or high-grade dysplasia, and 9.9% (357/3609) had adenomas > or =1 cm., Conclusions: The yield for a distal advanced adenomatous lesion when a polyp 0.5-0.9 cm is observed at FSG is substantial and is due to the presence of advanced histology in polyps <1 cm and to detection of polyps that measure > or =1.0 cm on colonoscopy. Establishing thresholds for observation versus evaluation will require careful assessment of the overall yield.
- Published
- 2006
- Full Text
- View/download PDF
26. Insulin-like growth factor-I and insulin are associated with the presence and advancement of adenomatous polyps.
- Author
-
Schoen RE, Weissfeld JL, Kuller LH, Thaete FL, Evans RW, Hayes RB, and Rosen CJ
- Subjects
- Adenomatous Polyps blood, Adenomatous Polyps epidemiology, Adipose Tissue metabolism, Age Distribution, Aged, Biomarkers, Tumor blood, Biopsy, Needle, Cohort Studies, Colonoscopy, Colorectal Neoplasms blood, Colorectal Neoplasms epidemiology, Female, Humans, Immunohistochemistry, Insulin analysis, Insulin-Like Growth Factor Binding Protein 1 analysis, Insulin-Like Growth Factor Binding Protein 3 analysis, Logistic Models, Male, Mass Screening, Middle Aged, Neoplasm Staging, Prevalence, Probability, Prognosis, Risk Assessment, Sensitivity and Specificity, Sex Distribution, Survival Analysis, Adenomatous Polyps pathology, Colorectal Neoplasms pathology, Insulin blood, Insulin-Like Growth Factor Binding Protein 1 blood, Insulin-Like Growth Factor Binding Protein 3 blood, Neoplasm Invasiveness pathology
- Abstract
Background & Aims: Insulin and insulin-like growth factor-I (IGF-I) affect proliferation, differentiation, and apoptosis and are potential risk factors for colorectal cancer (CRC). Visceral obesity, possibly via hyperinsulinemia, has also been linked to CRC risk. We evaluated the relationship of insulin, IGF-I, insulin-like growth factor binding protein (IGFBP) 3, and visceral adipose tissue (VAT) in subjects with adenomatous polyps, the precursor lesion of colorectal cancer., Methods: Participants were asymptomatic subjects who underwent screening flexible sigmoidoscopy (FSG) within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Subjects underwent single-slice, computerized tomography scanning to measure VAT and serum fasting insulin, IGF-I, and IGFBP-3 measurements., Results: Four hundred fifty-eight subjects were enrolled, of which 202 subjects had an adenoma, 70 of which were an advanced adenoma. IGF-I (P = .02), IGF-I/IGFBP-3 ratio (P = .003), and insulin (P = .02) were significantly increased in subjects with adenomas compared with controls. In an unadjusted logistic regression analysis using sex-specific quartile cut points, subjects in quartile 4 in comparison with quartile 1 of IGF-I (odds ratio [OR] = 1.7; [95% CI: 1.0-2.9], Ptrend = .03), IGF-I/IGFBP-3 ratio (OR = 1.9 [95% CI: 1.1-3.3], Ptrend = .01), and insulin (OR = 2.1 [95% CI: 1.2-3.6], Ptrend = .04) were at increased risk of adenoma. When limiting the case group to advanced adenomas, the effect was more pronounced: IGF-I (OR = 2.8 [95% CI: 1.3-6.2], Ptrend = .006), IGF-I/IGFBP-3 ratio (OR = 2.3, [95% CI: 1.0-5.2], Ptrend = .04), and insulin (OR = 2.3 [95% CI: 1.1-4.9], Ptrend = .14). Visceral adipose tissue was not associated with adenoma risk., Conclusions: Levels of IGF-I, ratio of IGF-I/IGFBP-3, and insulin are associated with adenomas and even more so with advanced adenomas. These data support the hypothesis that insulin and IGF-I may contribute to the development and advancement of adenomatous polyps.
- Published
- 2005
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.