Browsing by Subject "Colorectal neoplasms"
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Item A Modified Tumor-Node-Metastasis Classification for Primary Operable Colorectal Cancer(Oxford University Press, 2020-10-16) Zhang, Chundong; Mei, Zubing; Pei, Junpeng; Abe, Masanobu; Zeng, Xiantao; Huang, Qiao; Nishiyama, Kazuhiro; Akimoto, Naohiko; Haruki, Koichiro; Nan, Hongmei; Meyerhardt, Jeffrey A.; Zhang, Rui; Li, Xinxiang; Ogino, Shuji; Ugai, Tomotaka; Community and Global Health, School of Public HealthBackground: The American Joint Committee on Cancer (AJCC) 8th tumor-node-metastasis (TNM) classification for colorectal cancer (CRC) has limited ability to predict prognosis. Methods: We included 45 379 eligible stage I-III CRC patients from the Surveillance, Epidemiology, and End Results Program. Patients were randomly assigned individually to a training (n = 31 772) or an internal validation cohort (n = 13 607). External validation was performed in 10 902 additional patients. Patients were divided according to T and N stage permutations. Survival analyses were conducted by a Cox proportional hazard model and Kaplan-Meier analysis, with T1N0 as the reference. Area under receiver operating characteristic curve and Akaike information criteria were applied for prognostic discrimination and model fitting, respectively. Clinical benefits were further assessed by decision curve analyses. Results: We created a modified TNM (mTNM) classification: stages I (T1-2N0-1a); IIA (T1N1b, T2N1b, T3N0); IIB (T1-2N2a-2b, T3N1a-1b, T4aN0); IIC (T3N2a, T4aN1a-2a, T4bN0); IIIA (T3N2b, T4bN1a); IIIB (T4aN2b, T4bN1b); and IIIC (T4bN2a-2b). In the internal validation cohort, compared with the AJCC 8th TNM classification, the mTNM classification showed superior prognostic discrimination (area under receiver operating characteristic curve = 0.675 vs 0.667, respectively; 2-sided P < .001) and better model fitting (Akaike information criteria = 70 937 vs 71 238, respectively). Similar findings were obtained in the external validation cohort. Decision curve analyses revealed that the mTNM had superior net benefits over the AJCC 8th TNM classification in the internal and external validation cohorts. Conclusions: The mTNM classification provides better prognostic discrimination than AJCC 8th TNM classification, with good applicability in various populations and settings, to help better stratify stage I-III CRC patients into prognostic groups.Item Association of Body Mass Index With Colorectal Cancer Risk by Genome-Wide Variants(Oxford University Press, 2021) Campbell, Peter T.; Lin, Yi; Bien, Stephanie A.; Figueiredo, Jane C.; Harrison, Tabitha A.; Guinter, Mark A.; Berndt, Sonja I.; Brenner, Hermann; Chan, Andrew T.; Chang-Claude, Jenny; Gallinger, Steven J.; Gapstur, Susan M.; Giles, Graham G.; Giovannucci, Edward; Gruber, Stephen B.; Gunter, Marc; Hoffmeister, Michael; Jacobs, Eric J.; Jenkins, Mark A.; Marchand, Loic Le; Li, Li; McLaughlin, John R.; Murphy, Neil; Milne, Roger L.; Newcomb, Polly A.; Newton, Christina; Ogino, Shuji; Potter, John D.; Rennert, Gad; Rennert, Hedy S.; Robinson, Jennifer; Sakoda, Lori C.; Slattery, Martha L.; Song, Yiqing; White, Emily; Woods, Michael O.; Casey, Graham; Hsu, Li; Peters, Ulrike; Epidemiology, School of Public HealthBackground: Body mass index (BMI) is a complex phenotype that may interact with genetic variants to influence colorectal cancer risk. Methods: We tested multiplicative statistical interactions between BMI (per 5 kg/m2) and approximately 2.7 million single nucleotide polymorphisms with colorectal cancer risk among 14 059 colorectal cancer case (53.2% women) and 14 416 control (53.8% women) participants. All analyses were stratified by sex a priori. Statistical methods included 2-step (ie, Cocktail method) and single-step (ie, case-control logistic regression and a joint 2-degree of freedom test) procedures. All statistical tests were two-sided. Results: Each 5 kg/m2 increase in BMI was associated with higher risks of colorectal cancer, less so for women (odds ratio [OR] = 1.14, 95% confidence intervals [CI] = 1.11 to 1.18; P = 9.75 × 10-17) than for men (OR = 1.26, 95% CI = 1.20 to 1.32; P = 2.13 × 10-24). The 2-step Cocktail method identified an interaction for women, but not men, between BMI and a SMAD7 intronic variant at 18q21.1 (rs4939827; Pobserved = .0009; Pthreshold = .005). A joint 2-degree of freedom test was consistent with this finding for women (joint P = 2.43 × 10-10). Each 5 kg/m2 increase in BMI was more strongly associated with colorectal cancer risk for women with the rs4939827-CC genotype (OR = 1.24, 95% CI = 1.16 to 1.32; P = 2.60 × 10-10) than for women with the CT (OR = 1.14, 95% CI = 1.09 to 1.19; P = 1.04 × 10-8) or TT (OR = 1.07, 95% CI = 1.01 to 1.14; P = .02) genotypes. Conclusion: These results provide novel insights on a potential mechanism through which a SMAD7 variant, previously identified as a susceptibility locus for colorectal cancer, and BMI may influence colorectal cancer risk for women.Item Association of Coffee Intake With Survival in Patients With Advanced or Metastatic Colorectal Cancer(American Medical Association, 2020-11-01) Mackintosh, Christopher; Yuan, Chen; Ou, Fang-Shu; Zhang, Sui; Niedzwiecki, Donna; Chang, I-Wen; O’Neil, Bert H.; Mullen, Brian C.; Lenz, Heinz-Josef; Blanke, Charles D.; Venook, Alan P.; Mayer, Robert J.; Fuchs, Charles S.; Innocenti, Federico; Nixon, Andrew B.; Goldberg, Richard M.; O’Reilly, Eileen M.; Meyerhardt, Jeffrey A.; Ng, Kimmie; Medicine, School of MedicineImportance: Several compounds found in coffee possess antioxidant, anti-inflammatory, and insulin-sensitizing effects, which may contribute to anticancer activity. Epidemiological studies have identified associations between increased coffee consumption and decreased recurrence and mortality of colorectal cancer. The association between coffee consumption and survival in patients with advanced or metastatic colorectal cancer is unknown. Objective: To evaluate the association of coffee consumption with disease progression and death in patients with advanced or metastatic colorectal cancer. Design, setting, and participants: This prospective observational cohort study included 1171 patients with previously untreated locally advanced or metastatic colorectal cancer who were enrolled in Cancer and Leukemia Group B (Alliance)/SWOG 80405, a completed phase 3 clinical trial comparing the addition of cetuximab and/or bevacizumab to standard chemotherapy. Patients reported dietary intake using a semiquantitative food frequency questionnaire at the time of enrollment. Data were collected from October 27, 2005, to January 18, 2018, and analyzed from May 1 to August 31, 2018. Exposures: Consumption of total, decaffeinated, and caffeinated coffee measured in cups per day. Main outcomes and measures: Overall survival (OS) and progression-free survival (PFS). Results: Among the 1171 patients included in the analysis (694 men [59%]; median age, 59 [interquartile range, 51-67] years). The median follow-up time among living patients was 5.4 years (10th percentile, 1.3 years; IQR, 3.2-6.3 years). A total of 1092 patients (93%) had died or had disease progression. Increased consumption of coffee was associated with decreased risk of cancer progression (hazard ratio [HR] for 1-cup/d increment, 0.95; 95% CI, 0.91-1.00; P = .04 for trend) and death (HR for 1-cup/d increment, 0.93; 95% CI, 0.89-0.98; P = .004 for trend). Participants who consumed 2 to 3 cups of coffee per day had a multivariable HR for OS of 0.82 (95% CI, 0.67-1.00) and for PFS of 0.82 (95% CI, 0.68-0.99), compared with those who did not drink coffee. Participants who consumed at least 4 cups of coffee per day had a multivariable HR for OS of 0.64 (95% CI, 0.46-0.87) and for PFS of 0.78 (95% CI, 0.59-1.05). Significant associations were noted for both caffeinated and decaffeinated coffee. Conclusions and relevance: Coffee consumption may be associated with reduced risk of disease progression and death in patients with advanced or metastatic colorectal cancer. Further research is warranted to elucidate underlying biological mechanisms.Item Bacterial-Driven Inflammation and Mutant BRAF Expression Combine to Promote Murine Colon Tumorigenesis That Is Sensitive to Immune Checkpoint Therapy(American Association for Cancer Research, 2021) DeStefano Shields, Christina E.; White, James R.; Chung, Liam; Wenzel, Alyssa; Hicks, Jessica L.; Tam, Ada J.; Chan, June L.; Dejea, Christine M.; Fan, Hongni; Michel, John; Maiuri, Ashley R.; Sriramkumar, Shruthi; Podicheti, Ram; Rusch, Douglas B.; Wang, Hao; De Marzo, Angelo M.; Besharati, Sepideh; Anders, Robert A.; Baylin, Stephen B.; O’Hagan, Heather M.; Housseau, Franck; Sears, Cynthia L.; Medical and Molecular Genetics, School of MedicineColorectal cancer is multifaceted, with subtypes defined by genetic, histologic, and immunologic features that are potentially influenced by inflammation, mutagens, and/or microbiota. Colorectal cancers with activating mutations in BRAF are associated with distinct clinical characteristics, although the pathogenesis is not well understood. The Wnt-driven multiple intestinal neoplasia (MinApcΔ716/+) enterotoxigenic Bacteroides fragilis (ETBF) murine model is characterized by IL17-dependent, distal colon adenomas. Herein, we report that the addition of the BRAF V600E mutation to this model results in the emergence of a distinct locus of midcolon tumors. In ETBF-colonized BRAF V600E Lgr5 CreMin (BLM) mice, tumors have similarities to human BRAF V600E tumors, including histology, CpG island DNA hypermethylation, and immune signatures. In comparison to Min ETBF tumors, BLM ETBF tumors are infiltrated by CD8+ T cells, express IFNγ signatures, and are sensitive to anti-PD-L1 treatment. These results provide direct evidence for critical roles of host genetic and microbiota interactions in colorectal cancer pathogenesis and sensitivity to immunotherapy. SIGNIFICANCE: Colorectal cancers with BRAF mutations have distinct characteristics. We present evidence of specific colorectal cancer gene-microbial interactions in which colonization with toxigenic bacteria drives tumorigenesis in BRAF V600E Lgr5 CreMin mice, wherein tumors phenocopy aspects of human BRAF-mutated tumors and have a distinct IFNγ-dominant immune microenvironment uniquely responsive to immune checkpoint blockade.Item Beyond GWAS of Colorectal Cancer: Evidence of Interaction with Alcohol Consumption and Putative Causal Variant for the 10q24.2 Region(American Association for Cancer Research, 2022) Jordahl, Kristina M.; Shcherbina, Anna; Kim, Andre E.; Su, Yu-Ru; Lin, Yi; Wang, Jun; Qu, Conghui; Albanes, Demetrius; Arndt, Volker; Baurley, James W.; Berndt, Sonja I.; Bien, Stephanie A.; Bishop, D. Timothy; Bouras, Emmanouil; Brenner, Hermann; Buchanan, Daniel D.; Budiarto, Arif; Campbell, Peter T.; Carreras-Torres, Robert; Casey, Graham; Cenggoro, Tjeng Wawan; Chan, Andrew T.; Conti, David V.; Dampier, Christopher H.; Devall, Matthew A.; Díez-Obrero, Virginia; Dimou, Niki; Drew, David A.; Figueiredo, Jane C.; Gallinger, Steven; Giles, Graham G.; Gruber, Stephen B.; Gsur, Andrea; Gunter, Marc J.; Hampel, Heather; Harlid, Sophia; Harrison, Tabitha A.; Hidaka, Akihisa; Hoffmeister, Michael; Huyghe, Jeroen R.; Jenkins, Mark A.; Joshi, Amit D.; Keku, Temitope O.; Larsson, Susanna C.; Le Marchand, Loic; Lewinger, Juan Pablo; Li, Li; Mahesworo, Bharuno; Moreno, Victor; Morrison, John L.; Murphy, Neil; Nan, Hongmei; Nassir, Rami; Newcomb, Polly A.; Obón-Santacana, Mireia; Ogino, Shuji; Ose, Jennifer; Pai, Rish K.; Palmer, Julie R.; Papadimitriou, Nikos; Pardamean, Bens; Peoples, Anita R.; Pharoah, Paul D. P.; Platz, Elizabeth A.; Potter, John D.; Prentice, Ross L.; Rennert, Gad; Ruiz-Narvaez, Edward; Sakoda, Lori C.; Scacheri, Peter C.; Schmit, Stephanie L.; Schoen, Robert E.; Slattery, Martha L.; Stern, Mariana C.; Tangen, Catherine M.; Thibodeau, Stephen N.; Thomas, Duncan C.; Tian, Yu; Tsilidis, Konstantinos K.; Ulrich, Cornelia M.; van Duijnhoven, Franzel J. B.; Van Guelpen, Bethany; Visvanathan, Kala; Vodicka, Pavel; White, Emily; Wolk, Alicja; Woods, Michael O.; Wu, Anna H.; Zemlianskaia, Natalia; Chang-Claude, Jenny; Gauderman, W. James; Hsu, Li; Kundaje, Anshul; Peters, Ulrike; Epidemiology, Richard M. Fairbanks School of Public HealthBackground: Currently known associations between common genetic variants and colorectal cancer explain less than half of its heritability of 25%. As alcohol consumption has a J-shape association with colorectal cancer risk, nondrinking and heavy drinking are both risk factors for colorectal cancer. Methods: Individual-level data was pooled from the Colon Cancer Family Registry, Colorectal Transdisciplinary Study, and Genetics and Epidemiology of Colorectal Cancer Consortium to compare nondrinkers (≤1 g/day) and heavy drinkers (>28 g/day) with light-to-moderate drinkers (1-28 g/day) in GxE analyses. To improve power, we implemented joint 2df and 3df tests and a novel two-step method that modifies the weighted hypothesis testing framework. We prioritized putative causal variants by predicting allelic effects using support vector machine models. Results: For nondrinking as compared with light-to-moderate drinking, the hybrid two-step approach identified 13 significant SNPs with pairwise r2 > 0.9 in the 10q24.2/COX15 region. When stratified by alcohol intake, the A allele of lead SNP rs2300985 has a dose-response increase in risk of colorectal cancer as compared with the G allele in light-to-moderate drinkers [OR for GA genotype = 1.11; 95% confidence interval (CI), 1.06-1.17; OR for AA genotype = 1.22; 95% CI, 1.14-1.31], but not in nondrinkers or heavy drinkers. Among the correlated candidate SNPs in the 10q24.2/COX15 region, rs1318920 was predicted to disrupt an HNF4 transcription factor binding motif. Conclusions: Our study suggests that the association with colorectal cancer in 10q24.2/COX15 observed in genome-wide association study is strongest in nondrinkers. We also identified rs1318920 as the putative causal regulatory variant for the region. Impact: The study identifies multifaceted evidence of a possible functional effect for rs1318920.Item Coffee Intake of Colorectal Cancer Patients and Prognosis According to Histopathologic Lymphocytic Reaction and T-Cell Infiltrates(Elsevier, 2022) Ugai, Tomotaka; Haruki, Koichiro; Väyrynen, Juha P.; Borowsky, Jennifer; Fujiyoshi, Kenji; Lau, Mai Chan; Akimoto, Naohiko; Zhong, Rong; Kishikawa, Junko; Arima, Kota; Shi, Shan-shan; Zhao, Melissa; Fuchs, Charles S.; Zhang, Xuehong; Giannakis, Marios; Song, Mingyang; Nan, Hongmei; Meyerhardt, Jeffrey A.; Wang, Molin; Nowak, Jonathan A.; Ogino, Shuji; Community and Global Health, Richard M. Fairbanks School of Public HealthGiven previous biological evidence of immunomodulatory effects of coffee, we hypothesized that the association between coffee intake of colorectal cancer patients and survival differs by immune responses. Using a molecular pathological epidemiology database of 4,465 incident colorectal cancer cases, including 1,262 cases with molecular data, in the Nurses’ Health Study and the Health Professionals Follow-up Study, we examined the association between coffee intake of colorectal cancer patients and survival in strata of levels of histopathologic lymphocytic reaction and T-cell infiltrates in tumor tissue. We did not observe a significant association of coffee intake with colorectal cancer-specific mortality [multivariable-adjusted hazard ratio (HR) for one cup increase of coffee intake per day, 0.93; 95% confidence interval (CI), 0.84-1.03]. Although statistical significance was not reached at the stringent level (α=0.005), the association of coffee intake with colorectal cancer-specific mortality differed by Crohn's-like lymphoid reaction (Pinteraction=.007). Coffee intake was associated with lower colorectal cancer-specific mortality in patients with high Crohn's-like reaction (multivariable HR for one cup increase of coffee intake per day, 0.55; 95% CI, 0.37–0.81; Ptrend=.002), but not in patients with intermediate Crohn's-like reaction (the corresponding HR, 1.02; 95% CI, 0.72–1.44) or negative/low Crohn's-like reaction (the corresponding HR, 0.95; 95% CI, 0.83–1.07). The associations of coffee intake with colorectal cancer-specific mortality did not significantly differ by levels of other lymphocytic reaction or any T-cell subset (Pinteraction>.18). There is suggestive evidence for differential prognostic effects of coffee intake by Crohn’s-like lymphoid reaction in colorectal cancer.Item Colorectal Cancer Screening Programs in Latin America: A Systematic Review and Meta-Analysis(American Medical Association, 2024-02-05) Montalvan-Sanchez, Eleazar E.; Norwood, Dalton A.; Dougherty, Michael; Beas, Renato; Guranizo-Ortiz, Maria; Ramirez-Rojas, Miriam; Morgan, Douglas R.; Imperiale, Thomas F.; Medicine, School of MedicineImportance: Colorectal cancer (CRC) is a leading cause of cancer-related mortality globally, with increasing incidence and mortality in Latin America. CRC screening programs can reduce disease burden, but information on screening programs in Latin America is limited. Objective: To describe characteristics (eg, type of program, uptake, neoplastic yield) of CRC screening programs in Latin America. Data sources: PubMed, Ovid MEDLINE, EMBASE, Cochrane, PsycINFO, Web of Science Core Collection, LILACS, and SciELO were searched from inception to February 2023. Relevant references from bibliographies, conference proceedings, and gray literature were considered. The search strategy included English, Spanish, and Portuguese terms. Study selection: Included were studies of CRC screening programs in Latin America using fecal immunochemical test (FIT) or colonoscopy as the primary screening method. Four reviewers independently assessed study eligibility based on titles, with review of abstracts and full texts as needed. Data extraction and synthesis: Guidelines from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were followed for data abstraction and quality assessment. Descriptive information was extracted, and data were pooled using a random-effects model. Main outcomes and measures: Program performance indicators included rates of participation and FIT positivity, adenoma detection rate (ADR), advanced adenoma detection rate (AADR), CRC detection rate, and colonoscopy quality indicators. Results: There were 17 studies included from upper middle-income and high-income countries in Latin America with a total of 123 929 participants. Thirteen studies used FIT as the initial screening method, whereas 4 used screening colonoscopy. The participation rate in FIT-based programs was 85.8% (95% CI, 78.5%-91.4%). FIT positivity rates were 15.2% (95% CI, 9.6%-21.8%) for the 50-ng/mL threshold and 9.7% (95% CI, 6.8%-13.0%) for the 100-ng/mL threshold. For FIT-based studies, the pooled ADR was 39.0% (95% CI, 29.3%-49.2%) and CRC detection rate was 4.9% (95% CI, 2.6%-7.9%); for screening colonoscopy-based studies, the pooled ADR was 19.9% (95% CI, 15.5%-24.8%) and CRC detection rate was 0.4% (95% CI, 0.1%-0.8%). Conclusions and relevance: This systematic review and meta-analysis suggests that CRC screening in upper middle-income countries in Latin America is feasible, detecting rates of neoplasia comparable with those of high-income regions. Population-based screening programs should be developed or enhanced in these settings. There is a knowledge gap regarding feasibility and yield of screening programs in lower middle-income countries.Item Colorectal Dysplasia and Cancer in Pediatric-Onset Ulcerative Colitis Associated With Primary Sclerosing Cholangitis(Elsevier, 2021) El-Matary, Wael; Guthery, Stephen L.; Amir, Achiya Z.; DiGuglielmo, Matthew; Draijer, Laura G.; Furuya, Katryn N.; Gupta, Nitika; Hochberg, Jessica T.; Horslen, Simon; Kerkar, Nanda; Koot, Bart G. P.; Laborda, Trevor J.; Loomes, Kathleen M.; Mack, Cara; Martinez, Mercedes; Miethke, Alexander; Miloh, Tamir; Mogul, Douglas; Mohammed, Saeed; Moroz, Stacy; Ovchinsky, Nadia; Perito, Emily R.; Rao, Girish; Ricciuto, Amanda; Sathya, Pushpa; Schwarz, Kathleen B.; Shah, Uzma; Singh, Ruchi; Soufi, Nisreen; Valentino, Pamela L.; Zizzo, Andréanne; Deneau, Mark R.; Pediatrics, School of MedicineInflammatory bowel disease (IBD), especially when associated with primary sclerosing cholangitis (PSC), is a risk factor for developing colorectal cancer (CRC). We aimed to determine the incidence of CRC in a large cohort of pediatric-onset PSC-ulcerative colitis (UC) patients.Item Comparative Effectiveness of 2 Interventions to Increase Breast, Cervical, and Colorectal Cancer Screening Among Women in the Rural US: A Randomized Clinical Trial(American Medical Association, 2023-04-02) Champion, Victoria L.; Paskett, Electra D.; Stump, Timothy E.; Biederman, Erika B.; Vachon, Eric; Katz, Mira L.; Rawl, Susan M.; Baltic, Ryan D.; Kettler, Carla D.; Seiber, Eric E.; Xu, Wendy Y.; Monahan, Patrick O.; Biostatistics and Health Data Science, School of MedicineImportance: Women living in rural areas have lower rates of breast, cervical, and colorectal cancer screening compared with women living in urban settings. Objective: To assess the comparative effectiveness of (1) a mailed, tailored digital video disc (DVD) intervention; (2) a DVD intervention plus telephonic patient navigation (DVD/PN); and (3) usual care with simultaneously increased adherence to any breast, cervical, and colorectal cancer screening that was not up to date at baseline and to assess cost-effectiveness. Design, setting, and participants: This randomized clinical trial recruited and followed up women from rural Indiana and Ohio (community based) who were not up to date on any or all recommended cancer screenings. Participants were randomly assigned between November 28, 2016, and July 1, 2019, to 1 of 3 study groups (DVD, DVD/PN, or usual care). Statistical analyses were completed between August and December 2021 and between March and September 2022. Intervention: The DVD interactively assessed and provided messages for health beliefs, including risk of developing the targeted cancers and barriers, benefits, and self-efficacy for obtaining the needed screenings. Patient navigators counseled women on barriers to obtaining screenings. The intervention simultaneously supported obtaining screening for all or any tests outside of guidelines at baseline. Main outcomes and measures: Receipt of any or all needed cancer screenings from baseline through 12 months, including breast, cervical, and colorectal cancer, and cost-effectiveness of the intervention. Binary logistic regression was used to compare the randomized groups on being up to date for all and any screenings at 12 months. Results: The sample included 963 women aged 50 to 74 years (mean [SD] age, 58.6 [6.3] years). The DVD group had nearly twice the odds of those in the usual care group of obtaining all needed screenings (odds ratio [OR], 1.84; 95% CI, 1.02-3.43; P = .048), and the odds were nearly 6 times greater for DVD/PN vs usual care (OR, 5.69; 95% CI, 3.24-10.5; P < .001). The DVD/PN intervention (but not DVD alone) was significantly more effective than usual care (OR, 4.01; 95% CI, 2.60-6.28; P < .001) for promoting at least 1 (ie, any) of the needed screenings at 12 months. Cost-effectiveness per woman who was up to date was $14 462 in the DVD group and $10 638 in the DVD/PN group. Conclusions and relevance: In this randomized clinical trial of rural women who were not up to date with at least 1 of the recommended cancer screenings (breast, cervical, or colorectal), an intervention designed to simultaneously increase adherence to any or all of the 3 cancer screening tests was more effective than usual care, available at relatively modest costs, and able to be remotely delivered, demonstrating great potential for implementing an evidence-based intervention in remote areas of the midwestern US.Item Contribution of patient, physician, and environmental factors to demographic and health variation in colonoscopy follow-up for abnormal colorectal cancer screening test results(Wiley, 2017-09-15) Partin, Melissa R.; Gravely, Amy; Burgess, James F., Jr.; Haggstrom, David; Lillie, Sarah E.; Nelson, David B.; Nugent, Sean; Shaukat, Aasma; Sultan, Shahnaz; Walter, Louise C.; Burgess, Diana J.; Medicine, School of MedicineBACKGROUND: Patient, physician, and environmental factors were identified, and the authors examined the contribution of these factors to demographic and health variation in colonoscopy follow-up after a positive fecal occult blood test/fecal immunochemical test (FOBT/FIT) screening. METHODS: In total, 76,243 FOBT/FIT-positive patients were identified from 120 Veterans Health Administration (VHA) facilities between August 16, 2009 and March 20, 2011 and were followed for 6 months. Patient demographic (race/ethnicity, sex, age, marital status) and health characteristics (comorbidities), physician characteristics (training level, whether primary care provider) and behaviors (inappropriate FOBT/FIT screening), and environmental factors (geographic access, facility type) were identified from VHA administrative records. Patient behaviors (refusal, private sector colonoscopy use) were estimated with statistical text mining conducted on clinic notes, and follow-up predictors and adjusted rates were estimated using hierarchical logistic regression. RESULTS: Roughly 50% of individuals completed a colonoscopy at a VHA facility within 6 months. Age and comorbidity score were negatively associated with follow-up. Blacks were more likely to receive follow-up than whites. Environmental factors attenuated but did not fully account for these differences. Patient behaviors (refusal, private sector colonoscopy use) and physician behaviors (inappropriate screening) fully accounted for the small reverse race disparity and attenuated variation by age and comorbidity score. Patient behaviors (refusal and private sector colonoscopy use) contributed more to variation in follow-up rates than physician behaviors (inappropriate screening). CONCLUSIONS: In the VHA, blacks are more likely to receive colonoscopy follow-up for positive FOBT/FIT results than whites, and follow-up rates markedly decline with advancing age and comorbidity burden. Patient and physician behaviors explain race variation in follow-up rates and contribute to variation by age and comorbidity burden. Cancer 2017;123:3502-12. Published 2017. This article is a US Government work and is in the public domain in the USA.