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Item Association of Diet Quality With Survival Among People With Metastatic Colorectal Cancer in the Cancer and Leukemia B and Southwest Oncology Group 80405 Trial(AMA, 2020-10-30) Van Blarigan, Erin L.; Zhang, Sui; Ou, Fang-Shu; Venlo, Alan; Ng, Kimmie; Atreya, Chloe; Van Loon, Katherine; Niedzwiecki, Donna; Giovannucci, Edward; Wolfe, Eric G.; Lenz, Heinz-Josef; Innocenti, Federico; O'Neil, Bert H.; Shaw, James E.; Polite, Blase N.; Hochster, Howard S.; Atkins, James N.; Goldberg, Richard M.; Mayer, Robert J.; Blanke, Charles D.; O'Reilly, Eileen M.; Fuchs, Charles S.; Meyerhardt, Jeffrey A.; Medicine, School of MedicineImportance: Diet has been associated with survival in patients with stage I to III colorectal cancer, but data on patients with metastatic colorectal cancer are limited. Objective: To examine the association between diet quality and overall survival among individuals with metastatic colorectal cancer. Design, Setting, and Participants: This was a prospective cohort study of patients with metastatic colorectal cancer who were enrolled in the Cancer and Leukemia Group B (Alliance) and Southwest Oncology Group 80405 trial between October 27, 2005, and February 29, 2012, and followed up through January 2018. Exposures: Participants completed a validated food frequency questionnaire within 4 weeks after initiation of first-line treatment for metastatic colorectal cancer. Diets were categorized according to the Alternative Healthy Eating Index (AHEI), Alternate Mediterranean Diet (AMED) score, Dietary Approaches to Stop Hypertension (DASH) score, and Western and prudent dietary patterns derived using principal component analysis. Participants were categorized into sex-specific quintiles. Main Outcomes and Measures: Multivariable hazard ratios (HRs) and 95% CIs for overall survival. Results: In this cohort study of 1284 individuals with metastatic colorectal cancer, the median age was 59 (interquartile range [IQR]: 51-68) years, median body mass index was 27.2 (IQR, 24.1-31.4), 521 (41%) were female, and 1102 (86%) were White. There were 1100 deaths during a median follow-up of 73 months (IQR, 64-87 months). We observed an inverse association between the AMED score and risk of death (HR quintile 5 vs quintile 1, 0.83; 95% CI, 0.67-1.04; P = .04 for trend), but the point estimates were not statistically significant. None of the other diet scores or patterns were associated with overall survival. Conclusions and Relevance: In this prospective analysis of patients with metastatic colorectal cancer, diet quality assessed at initiation of first-line treatment for metastatic disease was not associated with overall survival.Item Consensus molecular subtyping of colorectal cancers is influenced by goblet cell content(Elsevier, 2021) Miller, Samuel A.; Ghobashi, Ahmed H.; O'Hagan, Heather M.; Medical and Molecular Genetics, School of MedicineA critical obstacle in the field of colorectal cancer (CRC) is the establishment of precise tumor subtypes to facilitate the development of targeted therapeutic regimens. While dysregulated mucin production is a histopathological feature of multiple CRC subtypes, it is not clear how well these pathologies are associated with the proportion of goblet cells in the tumor, or whether or not this proportion is variable across all CRC. This study demonstrates that consensus molecular subtype 3 (CMS3) CRC tumors and cell lines are enriched for the expression of goblet cell marker genes. Further, the proportion of goblet cells in the tumor is associated with the probability of CMS3 subtype assignment and these CMS3 subtype tumors are mutually exclusive from mucinous adenocarcinoma pathologies. This study provides proof of principle for the use of machine learning classification systems to subtype tumors based on cellular content, and provides further context regarding the features weighing CMS3 subtype assignment.Item Derivation and Validation of a Scoring System to Stratify Risk for Advanced Colorectal Neoplasia in Asymptomatic Adults: A Cross-sectional Study(American College of Physicians, 2015-09-01) Imperiale, Thomas F.; Monahan, Patrick O.; Stump, Timothy E.; Glowinski, Elizabeth A.; Ransohoff, David F.; Department of Medicine, IU School of MedicineBACKGROUND: Several methods are recommended equally strongly for colorectal cancer screening in average-risk persons. Risk stratification would enable tailoring of screening within this group, with less invasive tests (sigmoidoscopy or occult blood tests) for lower-risk persons and colonoscopy for higher-risk persons. OBJECTIVE: To create a risk index for advanced neoplasia (colorectal cancer and adenomas or serrated polyps ≥1.0 cm, villous histology, or high-grade dysplasia) anywhere in the colorectum, using the most common risk factors for colorectal neoplasia. DESIGN: Cross-sectional study. SETTING: Multiple endoscopy units, primarily in the Midwest. PATIENTS: Persons aged 50 to 80 years undergoing initial screening colonoscopy (December 2004 to September 2011). MEASUREMENTS: Derivation and validation of a risk index based on points from regression coefficients for age, sex, waist circumference, cigarette smoking, and family history of colorectal cancer. RESULTS: Among 2993 persons in the derivation set, prevalence of advanced neoplasia was 9.4%. Risks for advanced neoplasia in persons at very low, low, intermediate, and high risk were 1.92% (95% CI, 0.63% to 4.43%), 4.88% (CI, 3.79% to 6.18%), 9.93% (CI, 8.09% to 12.0%), and 24.9% (CI, 21.1% to 29.1%), respectively (P < 0.001). Sigmoidoscopy to the descending colon in the low-risk groups would have detected 51 of 70 (73% [CI, 61% to 83%]) advanced neoplasms. Among 1467 persons in the validation set, corresponding risks for advanced neoplasia were 1.65% (CI, 0.20% to 5.84%), 3.31% (CI, 2.08% to 4.97%), 10.9% (CI, 8.26% to 14.1%), and 22.3% (CI, 16.9% to 28.5%), respectively (P < 0.001). Sigmoidoscopy would have detected 21 of 24 (87.5% [CI, 68% to 97%]) advanced neoplasms. LIMITATIONS: Split-sample validation; results apply to first-time screening. CONCLUSION: This index stratifies risk for advanced neoplasia among average-risk persons by identifying lower-risk groups for which noncolonoscopy strategies may be effective and efficient and a higher-risk group for which colonoscopy may be preferred. PRIMARY FUNDING SOURCE: National Cancer Institute, Walther Cancer Institute, Indiana University Simon Cancer Center, and Indiana Clinical and Translational Sciences Institute.Item Development of a Research Agenda for the Management of Metastatic Colorectal Cancer: Proceedings from a Multidisciplinary Research Consensus Panel(Elsevier, 2012-02) d’Othée, Bertrand Janne; Sofocleous, Constantinos T.; Hanna, Nader; Lewandowski, Robert J.; Soulen, Michael C.; Vauthey, Jean-Nicolas; Cohen, Steven J.; Venook, Alan P.; Johnson, Matthew S.; Kennedy, Andrew S.; Murthy, Ravi; Geschwind, Jean-Francois; Kee, Stephen T.; Department of Radiology and Imaging Sciences, IU School of MedicineItem Exploratory genome-wide interaction analysis of non-steroidal anti-inflammatory drugs and predicted gene expression on colorectal cancer risk(American Association for Cancer Research, 2020-09) Wang, Xiaoliang; Su, Yu-Ru; Petersen, Paneen S.; Bien, Stephanie; Schmit, Stephanie L.; Drew, David A.; Albanes, Demetrius; Berndt, Sonja I.; Brenner, Hermann; Campbell, Peter T.; Casey, Graham; Chang-Claude, Jenny; Gallinger, Steven J.; Gruber, Stephen B.; Haile, Robert W.; Harrison, Tabitha A.; Hoffmeister, Michael; Jacobs, Eric J.; Jenkins, Mark A.; Joshi, Amit D.; Li, Li; Lin, Yi; Lindor, Noralane M.; Le Marchand, Loïc; Martin, Vicente; Milne, Roger; Maclnnis, Robert; Moreno, Victor; Nan, Hongmei; Newcomb, Polly A.; Potter, John D.; Rennert, Gad; Rennert, Hedy; Slattery, Martha L.; Thibodeau, Steve N.; Weinstein, Stephanie J.; Woods, Michael O.; Chan, Andrew T.; White, Emily; Hsu, Li; Peters, Ulrike; Global Health, School of Public HealthBackground: Regular use of nonsteroidal anti-inflammatory drugs (NSAID) is associated with lower risk of colorectal cancer. Genome-wide interaction analysis on single variants (G × E) has identified several SNPs that may interact with NSAIDs to confer colorectal cancer risk, but variations in gene expression levels may also modify the effect of NSAID use. Therefore, we tested interactions between NSAID use and predicted gene expression levels in relation to colorectal cancer risk. Methods: Genetically predicted gene expressions were tested for interaction with NSAID use on colorectal cancer risk among 19,258 colorectal cancer cases and 18,597 controls from 21 observational studies. A Mixed Score Test for Interactions (MiSTi) approach was used to jointly assess G × E effects which are modeled via fixed interaction effects of the weighted burden within each gene set (burden) and residual G × E effects (variance). A false discovery rate (FDR) at 0.2 was applied to correct for multiple testing. Results: Among the 4,840 genes tested, genetically predicted expression levels of four genes modified the effect of any NSAID use on colorectal cancer risk, including DPP10 (PG×E = 1.96 × 10-4), KRT16 (PG×E = 2.3 × 10-4), CD14 (PG×E = 9.38 × 10-4), and CYP27A1 (PG×E = 1.44 × 10-3). There was a significant interaction between expression level of RP11-89N17 and regular use of aspirin only on colorectal cancer risk (PG×E = 3.23 × 10-5). No interactions were observed between predicted gene expression and nonaspirin NSAID use at FDR < 0.2. Conclusions: By incorporating functional information, we discovered several novel genes that interacted with NSAID use.Item Financial hardship is associated with lower uptake of colorectal, breast, and cervical cancer screenings(Springer, 2021-10) Kasting, Monica L.; Haggstrom, David A.; Lee, Joy L.; Dickinson, Stephanie L.; Shields, Cleveland G.; Rawl, Susan M.; School of NursingPURPOSE: Cancer screening uptake differs between groups in ways that cannot be explained by socioeconomic status alone. This study examined associations between material, psychosocial, and behavioral aspects of financial hardship and cancer screening behaviors. METHODS: Surveys were mailed to 7,979 people ages 18-75 who were seen in the statewide health system in Indiana. Participants reported SES, feelings about finances, and whether they had to forgo medical care due to cost. This was compared to uptake of mammogram, colonoscopy/sigmoidoscopy, and Pap testing in best-fit multivariable logistic regression analyses controlling for demographic and healthcare characteristics. RESULTS: A total of 970 surveys were returned; the majority of respondents were female (54%), non-Hispanic White (75%), and over 50 years old (76%). 15% reported forgoing medical care due to cost; this barrier was higher among Black than White participants (24% vs. 13%; p = 0.001). In a best fit regression model for colonoscopy/sigmoidoscopy, those who reported they had to forgo medical care due to cost had lower odds of screening (aOR 0.41; 95% CI 0.22-0.74). Forgoing medical care due to cost was not significantly associated with Pap testing in bivariate analyses. For mammogram, forgoing medical care due to cost was significant in bivariate analyses (OR 0.44; 95% CI 0.22-0.88), but was not significant in the multivariable model. CONCLUSION: Associations between financial hardship and cancer screening suggest the need to reduce barriers to cancer screening even among patients who have access to healthcare. Future research should explore barriers related to both healthcare and personal costs.Item IGF-Binding Proteins, Adiponectin, and Survival in Metastatic Colorectal Cancer: Results From CALGB (Alliance)/SWOG 80405(Oxford University Press, 2020-08-27) Guercio, Brendan J.; Zhang, Sui; Ou, Fang-Shu; Venook, Alan P.; Niedzwiecki, Donna; Lenz, Heinz-Josef; Innocenti, Federico; Pollak, Michael N.; Nixon, Andrew B.; Mullen, Brian C.; O'Neil, Bert H.; Shaw, James E.; Polite, Blase N.; Benson, Al Bowen, III.; Atkins, James N.; Goldberg, Richard M.; Brown, Justin C.; O'Reilly, Eileen M.; Mayer, Robert J.; Blanke, Charles D.; Fuchs, Charles S.; Meyerhardt, Jeffrey A.; Medicine, School of MedicineBackground: Energy balance-related biomarkers are associated with risk and prognosis of various malignancies. Their relationship to survival in metastatic colorectal cancer (mCRC) requires further study. Methods: Baseline plasma insulin-like growth factor (IGF)-1, IGF-binding protein (IGFBP)-3, IGFBP-7, C-peptide, and adiponectin were measured at time of trial registration in a prospective cohort of patients with mCRC participating in a National Cancer Institute-sponsored trial of first-line systemic therapy. We used Cox proportional hazards regression to adjust for confounders and examine associations of each biomarker with overall survival (OS) and progression-free survival (PFS). P values are 2-sided. Results: Median follow-up for 1086 patients was 6.2 years. Compared with patients in the lowest IGFBP-3 quintile, patients in the highest IGFBP-3 quintile experienced an adjusted hazard ratio (HR) for OS of 0.57 (95% confidence interval [CI] = 0.42 to 0.78; P nonlinearity < .001) and for PFS of 0.61 (95% CI = 0.45 to 0.82; P trend = .003). Compared with patients in the lowest IGFBP-7 quintile, patients in the highest IGFBP-7 quintile experienced an adjusted hazard ratio for OS of 1.60 (95% CI = 1.30 to 1.97; P trend < .001) and for PFS of 1.38 (95% CI = 1.13 to 1.69; P trend < .001). Plasma C-peptide and IGF-1 were not associated with patient outcomes. Adiponectin was not associated with OS; there was a nonlinear U-shaped association between adiponectin and PFS (P nonlinearity = .03). Conclusions: Among patients with mCRC, high plasma IGFBP-3 and low IGFBP-7 were associated with longer OS and PFS. Extreme levels of adiponectin were associated with shorter PFS. These findings suggest potential avenues for prognostic and therapeutic innovation.Item Integrating men's health and masculinity theories to explain colorectal cancer screening behavior(Sage Publications, 2014-01) Christy, Shannon M.; Mosher, Catherine E.; Rawl, Susan M.; Department of Psychology, School of ScienceColorectal cancer (CRC) is the third most common cause of cancer deaths among men in the United States. Although CRC screening has been found to reduce CRC incidence and mortality, current screening rates among men are suboptimal due to various practical and psychosocial barriers. One potential barrier to CRC screening identified in qualitative studies with men is the threat to masculinity that endoscopic screening methods pose. Indeed, beliefs about masculinity have been predictive of other preventive health behaviors among men. In this review article, we propose a novel conceptual framework to explain men's CRC screening behavior that integrates masculinity norms, gender role conflict, men's health care experiences, behaviors, and beliefs, and social and background variables. This framework has the potential to guide future research on men's CRC screening behaviors and other health behaviors and may inform gender-sensitive interventions that target masculinity beliefs to increase preventive health behaviors.Item Pathway and network analysis in proteomics(Elsevier, 2014-12-07) Wu, Xiaogang; Hasan, Mohammad Al; Chen, Jake Yue; Department of BioHealth Informatics, School of Informatics and ComputingProteomics is inherently a systems science that studies not only measured protein and their expressions in a cell, but also the interplay of proteins, protein complexes, signaling pathways, and network modules. There is a rapid accumulation of Proteomics data in recent years. However, Proteomics data are highly variable, with results sensitive to data preparation methods, sample condition, instrument types, and analytical methods. To address the challenge in Proteomics data analysis, we review current tools being developed to incorporate biological function and network topological information. We categorize these tools into four types: tools with basic functional information and little topological features (e.g., GO category analysis), tools with rich functional information and little topological features (e.g., GSEA), tools with basic functional information and rich topological features (e.g., Cytoscape), and tools with rich functional information and rich topological features (e.g., PathwayExpress). We first review the potential application of these tools to Proteomics; then we review tools that can achieve automated learning of pathway modules and features, and tools that help perform integrated network visual analytics.Item Predictors of stage of adoption for colorectal cancer screening among African American primary care patients(Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins, 2014-07) Wang, Hsiao-Lan; Christy, Shannon M.; Skinner, Celette S.; Champion, Victoria L.; Springston, Jeffrey K.; Perkins, Susan M.; Tong, Yan; Krier, Connie; Gebregziabher, Netsanet; Rawl, Susan M.; Department of Psychology, School of ScienceBACKGROUND: Compared with other racial groups, African Americans have the highest colorectal cancer (CRC) incidence and mortality rates coupled with lower screening rates. OBJECTIVE: Our study examined the predictors of stage of adoption for fecal occult blood testing (FOBT) and colonoscopy among African American primary care patients who were nonadherent to published screening guidelines. METHODS: Baseline data (N = 815) in a randomized clinical trial were analyzed. Participants were categorized into precontemplation, contemplation, and preparation stages for FOBT and colonoscopy. Predictor variables were demographics, clinical variables, CRC health beliefs and knowledge, and social support. Hierarchical modeling was to identify significant predictors of stage of adoption. RESULTS: Older, male, Veterans Affairs participants and those with higher perceived self-efficacy, family/friend encouragement, and a provider recommendation had higher odds of being at a more advanced stage of adoption for FOBT. Patients with a history of cancer and higher perceived barriers had higher odds of being at an earlier stage of adoption for FOBT. Predictors of more advanced stage of adoption for colonoscopy included higher perceived benefits, higher perceived self-efficacy, family/friend encouragement, and a provider recommendation for colonoscopy. Higher income (>30 000 vs <15 000) was predictive of earlier stage of adoption for colonoscopy. CONCLUSIONS: Enhancing self-efficacy, encouragement from family and friends, and provider recommendations are important components of interventions to promote CRC screening. IMPLICATIONS FOR PRACTICE: Nurses can use knowledge of the characteristics associated with stage of adoption to educate and motivate their African American primary care patients to complete CRC screening tests.