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Obtaining comprehensive family health history (FHH) to inform colorectal cancer (CRC) risk management in primary care settings is challenging.To examine the effectiveness of a patient-facing FHH platform to identify and manage patients at increased CRC risk.Two-site, two-arm, cluster-randomized, implementation-effectiveness trial with primary care providers (PCPs) randomized to immediate intervention versus wait-list control.PCPs treating patients at least one half-day per week; patients aged 40-64 with no medical conditions that increased CRC risk.Immediate-arm patients entered their FHH into a web-based platform that provided risk assessment and guideline-driven decision support; wait-list control patients did so 12 months later.McNemar's test examined differences between the platform and electronic medical record (EMR) in rates of increased risk documentation. General estimating equations using logistic regression models compared arms in risk-concordant provider actions and patient screening test completion. Referral for genetic consultation was analyzed descriptively.Seventeen PCPs were randomized to each arm. Patients (n = 252 immediate, n = 253 control) averaged 51.4 (SD = 7.2) years, with 83% assigned male at birth, 58% White persons, and 33% Black persons. The percentage of patients identified as increased risk for CRC was greater with the platform (9.9%) versus EMR (5.2%), difference = 4.8% (95% CI: 2.6%, 6.9%), p.0001. There was no difference in PCP risk-concordant action [odds ratio (OR) = 0.7, 95% CI (0.4, 1.2; p = 0.16)]. Among 177 patients with a risk-concordant screening test ordered, there was no difference in test completion, OR = 0.8 [0.5,1.3]; p = 0.36. Of 50 patients identified by the platform as increased risk, 78.6% immediate and 68.2% control patients received a recommendation for genetic consultation, of which only one in each arm had a referral placed.FHH tools could accurately assess and document the clinical needs of patients at increased risk for CRC. Barriers to acting on those recommendations warrant further exploration.ClinicalTrials.gov NCT02247336 https://clinicaltrials.gov/ct2/show/NCT02247336.

Colorectal cancer (CRC) screening guidelines recommend frequent colonoscopies and consideration of genetic testing in individuals with ≥10 cumulative adenomas. However, it is unclear how these guidelines apply to routine practice. We estimated the proportion of participants found to have ≥10 cumulative adenomas in a screening population and described their outcomes of advanced neoplasia (AN), CRC, and extra-colonic malignancy. We performed a secondary analysis of VA CSP#380, which includes 3121 veterans aged 50–75 who were followed up to 10 years after screening colonoscopy. We calculated the cumulative risk of ≥10 cumulative adenomas by Kaplan–Meier method. We compared baseline risk factors in those with and without ≥10 cumulative adenomas as well as the risk for AN (adenoma ≥1 cm, villous adenoma or high-grade dysplasia, or CRC) and extra-colonic malignancy by multivariate logistic regression. The cumulative risk of ≥10 cumulative adenomas over 10.5 years was 6.51% (95% CI 4.38%–9.62%). Age 60–69 or 70–75 at baseline colonoscopy was the only factors associated with the finding of ≥10 cumulative adenomas. Compared to those with 0–9 cumulative adenomas, participants with ≥10 cumulative adenomas were more likely to have had AN (OR 17.03; 95% CI 9.41–30.84), including CRC (OR 7.00; 95% CI 2.84–17.28), but not extra-colonic malignancies. Approximately 6.5% of participants in this screening population were found to have ≥10 cumulative adenomas over 10.5 years, which was uncommon before age 60. These participants were found to have AN and CRC significantly more often compared to those with lower cumulative adenomas.

Understanding patient accumulation of comorbidities can facilitate healthcare strategy and personalized preventative care. We applied a directed network graph to electronic health record (EHR) data and characterized comorbidities in a cohort of healthy veterans undergoing screening colonoscopy. The Veterans Affairs Cooperative Studies Program #380 was a prospective longitudinal study of screening and surveillance colonoscopy. We identified initial instances of three-digit ICD-9 diagnoses for participants with at least 5 years of linked EHR history (October 1999 to December 2015). For diagnoses affecting at least 10% of patients, we calculated pairwise chronological relative risk (RR). iGraph was used to produce directed graphs of comorbidities with RR > 1, as well as summary statistics, key diseases, and communities. A directed graph based on 2210 patients visualized longitudinal development of comorbidities. Top hub (preceding) diseases included ischemic heart disease, inflammatory and toxic neuropathy, and diabetes. Top authority (subsequent) diagnoses were acute kidney failure and hypertensive chronic kidney failure. Four communities of correlated comorbidities were identified. Close analysis of top hub and authority diagnoses demonstrated known relationships, correlated sequelae, and novel hypotheses. Directed network graphs portray chronologic comorbidity relationships. We identified relationships between comorbid diagnoses in this aging veteran cohort. This may direct healthcare prioritization and personalized care.

The NCCN Guidelines for Colorectal Cancer (CRC) Screening describe various colorectal screening modalities as well as recommended screening schedules for patients at average or increased risk of developing sporadic CRC. They are intended to aid physicians with clinical decision-making regarding CRC screening for patients without defined genetic syndromes. These NCCN Guidelines Insights focus on select recent updates to the NCCN Guidelines, including a section on primary and secondary CRC prevention, and provide context for the panel’s recommendations regarding the age to initiate screening in average risk individuals and follow-up for low-risk adenomas.

INTRODUCTION Limited data inform the current postpolypectomy surveillance guidelines, which suggest a shortened interval to third colonoscopy after a negative second examination if high-risk adenomas (HRA) were present on the initial screening colonoscopy. Therefore, we examined the risk of HRA at third colonoscopy stratified by findings on 2 previous examinations in a prospective screening colonoscopy cohort of US veterans. METHODS We identified participants who had 3 or more colonoscopies from CSP#380. We examined the risk of HRA on the third examination based on findings from the previous 2 examinations. Multivariate logistic regression was used to adjust for multiple covariates. RESULTS HRA were found at the third examination in 114 (12.8%) of 891 participants. Those with HRA on both previous examinations had the greatest incidence of HRA at third examination (14/56, 25.0%). Compared with those with no adenomas on both previous examinations, participants with HRA on the first examination remained at significantly increased risk for HRA at the third examination at 3 years after a negative second examination (odds ratio [OR] 3.41, 95% confidence interval [CI] 1.28-9.08), 5 years (OR 3.14, 95% CI 1.49-6.61), and 7 years (OR 2.89, 95% CI 1.08-7.74). DISCUSSION In a screening population, HRA on the first examination identified individuals who remained at increased risk for HRA at the third examination, even after a negative second examination. This finding supports current colorectal cancer surveillance guidelines, which suggest a shortened, 5-year time interval to third colonoscopy after a negative second examination if high-risk findings were present on the baseline examination.

Controversy exists regarding the impact of various risk factors on noncolorectal cancer (CRC) mortality in healthy screening populations. We examined the impact of known CRC risk factors, including baseline colonoscopy findings, on non-CRC mortality in a screening population.Cooperative Studies Program (CSP) #380 is comprised of 3,121 veterans aged 50-75 years who underwent screening colonoscopy from 1994 to 97 and were then followed for at least 10 years or until death. Hazard ratios (HRs) for risk factors on non-CRC mortality were estimated by multivariate Cox proportional hazards.Current smoking (HR 2.12, 95% confidence interval [CI] 1.78-2.52, compared with nonsmokers) and physical activity (HR 0.89, 95% CI 0.84-0.93) were the modifiable factors most associated with non-CRC mortality in CSP#380. In addition, compared with no neoplasia at baseline colonoscopy, non-CRC mortality was higher in participants with ≥3 small adenomas (HR 1.43, 95% CI 1.06-1.94), advanced adenomas (HR 1.32, 95% CI 0.99-1.75), and CRC (HR 2.95, 95% CI 0.98-8.85). Those with 1-2 small adenomas were not at increased risk for non-CRC mortality (HR 1.15, 95% CI 0.94-1.4).In a CRC screening population, known modifiable risk factors were significantly associated with 10-year non-CRC mortality. Furthermore, those who died from non-CRC causes within 10 years were more likely to have had high-risk findings at baseline colonoscopy. These results suggest that advanced colonoscopy findings may be a risk marker of poor health outcomes. Integrated efforts are needed to motivate healthy lifestyle changes during CRC screening, particularly in those with high-risk colonoscopy findings and unaddressed risk factors.

Data are limited regarding colonoscopy risk during long-term, programmatic colorectal cancer screening and follow-up. We aimed to describe adverse events during follow-up in a colonoscopy screening program after the baseline examination and examine factors associated with increased risk.Cooperative Studies Program no. 380 includes 3121 asymptomatic veterans aged 50 to 75 years who underwent screening colonoscopy between 1994 and 1997. Periprocedure adverse events requiring significant intervention were defined as major events (other events were minor) and were tracked during follow-up for at least 10 years. Multivariable odds ratios (ORs) were calculated for factors associated with risk of follow-up adverse events.Of 3727 follow-up examinations in 1983 participants, adverse events occurred in 105 examinations (2.8%) in 93 individuals, including 22 major and 87 minor events (examinations may have had1 event). Incidence of major events (per 1000 examinations) remained relatively stable over time, with 6.1 events at examination 2, 4.8 at examination 3, and 7.2 at examination 4. Examinations with major events included 1 perforation, 3 GI bleeds requiring intervention, and 17 cardiopulmonary events. History of prior colonoscopic adverse events was associated with increased risk of events (major or minor) during follow-up (OR, 2.7; 95% confidence interval, 1.6-4.6).Long-term programmatic screening and surveillance was safe, as major events were rare during follow-up. However, serious cardiopulmonary events were the most common major events. These results highlight the need for detailed assessments of comorbid conditions during routine clinical practice, which could help inform individual decisions regarding the utility of ongoing colonoscopy follow-up.

Background: Approximately 697,000 members of the U.S. Armed Forces were deployed to the Persian Gulf in support of the 1990–1991 Persian Gulf War (GW). Subsequently, many deployed and some non-deployed veterans developed a chronic multi-symptom illness, now named Gulf War Illness (GWI). This manuscript outlines the methods and rationale for studying the genomics of GWI within the Million Veteran Program (MVP), a VA-based national research program that has linked medical records, surveys, and genomic data, enabling genome-wide association studies (GWASs). Methods: MVP participants who served in the military during the GW era were contacted by mail and invited to participate in the GWI study. A structured health questionnaire, based on a previously tested instrument, was also included in the mailing. Data on deployment locations and exposures, symptoms associated with GWI, clinical diagnoses, personal habits, and health care utilization were collected. Self-reported data will be augmented with chart reviews and structured international classification of disease codes, to classify participants by GWI case status. We will develop a phenotyping algorithm, based on two commonly used case definitions, to determine GWI status, and then conduct a nested case-control GWAS. Genetic variants associated with GWI will be investigated, and gene–gene and gene–environment interactions studied. The genetic overlap of GWI with, and causative mechanisms linking this illness to, other health conditions and the effects of genomic regulatory mechanisms on GWI risk will also be explored. Conclusions: The proposed initial GWAS described in this report will investigate the genomic underpinnings of GWI with a large sample size and state-of-the-art genomic analyses and phenotyping. The data generated will provide a rich and expansive foundation on which to build additional analyses.

Identifying individuals with hereditary syndromes allows for improved cancer surveillance, risk reduction, and optimized management. Establishing criteria for assessment allows for the identification of individuals who are carriers of pathogenic genetic variants. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provide recommendations for the assessment and management of patients with high-risk colorectal cancer syndromes. These NCCN Guidelines Insights focus on criteria for the evaluation of Lynch syndrome and considerations for use of multigene testing in the assessment of hereditary colorectal cancer syndromes.

Purpose The growing number of colorectal cancer (CRC) survivors often have multiple chronic conditions. Comparing nonmetastatic CRC survivors and matched noncancer controls, our objectives were to determine the odds of CRC survivors being diagnosed with cardiovascular disease (CVD)-related chronic conditions and their likelihood of control during the year after CRC diagnosis. Patients and methods We retrospectively identified patients diagnosed with nonmetastatic CRC in the Veterans Affairs health care system from fiscal years 2009 to 2012 and matched each with up to 3 noncancer control patients. We used logistic regression to assess differences in the likelihood of being diagnosed with CVD-related chronic conditions and control between nonmetastatic CRC survivors and noncancer controls. Results We identified 9,758 nonmetastatic CRC patients and matched them to 29,066 noncancer controls. At baseline, 69.4% of CRC survivors and their matched controls were diagnosed with hypertension, 52.4% with hyperlipidemia, and 36.7% with diabetes. Compared to matched noncancer controls, CRC survivors had 57% higher odds of being diagnosed with hypertension (OR=1.57, 95% CI=1.49-1.64) and 7% higher odds of controlled blood pressure (OR=1.07, 95% CI 1.02, 1.13) in the subsequent year. Compared to matched noncancer control patients, CRC survivors had half the odds of being diagnosed with hyperlipidemia (OR=0.50, 95% CI=0.48-0.52) and lower odds of low-density lipoprotein (LDL) control (OR 0.88, 95% CI 0.81-0.94). There were no significant differences between groups for diabetes diagnoses or control. Conclusion Compared to noncancer controls, nonmetastatic CRC survivors have 1) greater likelihood of being diagnosed with hypertension and worse blood pressure control in the year following diagnosis; 2) lower likelihood of being diagnosed with hyperlipidemia or LDL control; and 3) comparable diabetes diagnoses and control. There may be a need for hypertension control interventions targeting cancer survivors.

Precision medicine promises to improve patient outcomes, but much is unknown about its adoption within health-care systems. A comprehensive implementation plan is needed to realize its benefits. We convened 80 stakeholders for agenda setting to inform precision medicine policy, delivery, and research. Conference proceedings were audio-recorded, transcribed, and thematically analyzed. We mapped themes representing opportunities, challenges, and implementation strategies to a logic model, and two implementation science frameworks provided context. The logic model components included inputs: precision medicine infrastructure (clinical, research, and information technology), big data (from data sources to analytics), and resources (e.g., workforce and funding); activities: precision medicine research, practice, and education; outputs: precision medicine diagnosis; outcomes: personal utility, clinical utility, and health-care utilization; and impacts: precision medicine value, equity and access, and economic indicators. Precision medicine implementation challenges include evidence gaps demonstrating precision medicine utility, an unprepared workforce, the need to improve precision medicine access and reduce variation, and uncertain impacts on health-care utilization. Opportunities include integrated health-care systems, partnerships, and data analytics to support clinical decisions. Examples of implementation strategies to promote precision medicine are: changing record systems, data warehousing techniques, centralized technical assistance, and engaging consumers. We developed a theory-based, context-specific logic model that can be used by health-care organizations to facilitate precision medicine implementation.

Background & Aims Colorectal cancer is common yet largely preventable. The fecal immunochemical test (FIT) is a highly recommended screening method, but patients with positive results must receive a follow-up colonoscopy to determine if they have precancerous or cancerous lesions. We characterized colonoscopic follow-up evaluations and reasons for lack of follow-up in a Veterans Affairs (VA) cohort. Methods We conducted a retrospective cross-sectional analysis of patients 50 to 75 years old with a positive FIT result from January 1, 2014, through May 31, 2016, in a network of 12 VAs sites in southern California. We determined the proportion of patients who received a follow-up colonoscopy, median time to colonoscopy, and colonoscopy findings. For patients who did not undergo colonoscopy, we determined the documented reason for lack of colonoscopy and factors associated with declining the colonoscopy examination. Results Of the 10,635 FITs performed, 916 (8.6%) produced positive results; 569 of these (62.1%) were followed by colonoscopy. The median time to colonoscopy after a positive FIT result was 83 days (interquartile range, 54–145 d), which did not vary between veterans who received a colonoscopy at a VA facility (81 d; interquartile range, 52–143 d) vs a non-VA site (87 d; interquartile range, 60–154 d) (P = .2). For the 347 veterans (37.9%) who did not undergo follow-up colonoscopy, the reasons were patient-related (49.3%), provider-related (16.4%), system-related (12.1%), or multifactorial (22.2%). Overall, patient decline of colonoscopy (35.2%) was the most common reason. Conclusions In a cohort of veterans with positive results from FITs during CRC screening, reasons for lack of follow-up colonoscopy varied and included patient, provider, and system factors. These findings can be used to reduce barriers to follow-up colonoscopy and to address system-level challenges in scheduling and attrition for colonoscopy.

Purpose Cancer ascertainment using large-scale electronic health records is a challenge. Our aim was to propose and apply a structured approach for evaluating multiple candidate approaches for cancer ascertainment using colorectal cancer (CRC) ascertainment within the US Department of Veterans Affairs (VA) as a use case. Methods The proposed approach for evaluating cancer ascertainment strategies includes assessment of individual strategy performance, comparison of agreement across strategies, and review of discordant diagnoses. We applied this approach to compare three strategies for CRC ascertainment within the VA: administrative claims data consisting of International Classification of Diseases, Ninth Revision (ICD9) diagnosis codes; the VA Central Cancer Registry (VACCR); and the newly accessible Oncology Domain, consisting of cases abstracted by local cancer registrars. The study sample consisted of 1,839,043 veterans with index colonoscopy performed from 1999 to 2014. Strategy-specific performance was estimated based on manual record review of 100 candidate CRC cases and 100 colonoscopy controls. Strategies were further compared using Cohen’s κ and focused review of discordant CRC diagnoses. Results A total of 92,197 individuals met at least one CRC definition. All three strategies had high sensitivity and specificity for incident CRC. However, the ICD9-based strategy demonstrated poor positive predictive value (58%). VACCR and Oncology Domain had almost perfect agreement with each other (κ, 0.87) but only moderate agreement with ICD9-based diagnoses (κ, 0.51 and 0.57, respectively). Among discordant cases reviewed, 15% of ICD9-positive but VACCR- or Oncology Domain–negative cases had incident CRC. Conclusion Evaluating novel strategies for identifying cancer requires a structured approach, including validation against manual record review, agreement among candidate strategies, and focused review of discordant findings. Without careful assessment of ascertainment methods, analyses may be subject to bias and limited in clinical impact.

Federal agencies, including the Department of Veterans Affairs (VA), have prioritized improved access to scientific data and results collected through federally funded research. Our VA Cooperative Studies Program Epidemiology Center in Durham, North Carolina (CSPEC-Durham) assembled a repository of data and specimens collected through multiple studies on Veteran health issues to facilitate future research in these areas. We developed a single protocol, request process that includes scientific and ethical review of all applications, and a database architecture using metadata (common variable descriptors) to securely store and share data across diverse studies. In addition, we created a mechanism to allow data and specimens collected through older studies in which re-use was not addressed in the study protocol or consent forms to be shared if the future research is within the scope of the original consent. Our CSPEC-Durham Data and Specimen Repository currently includes research data, genomic data, and study specimens (e.g., DNA, blood) for three content areas: colorectal cancer, amyotrophic lateral sclerosis, and Gulf War research. The linking of the study specimens and research data can support additional genetic analyses and related research to improve Veterans' health.

Aims Gulf War illness (GWI), a chronic symptom-based disorder, affects up to 30% of Veterans who served in the 1990-1991 Gulf War1. Because no diagnostic test or code for GWI exists, researchers typically determine case status using self-reported symptoms and conditions according to Kansas2 and CDC3 criteria. No validated algorithm has been published and case definitions have varied slightly by study. This paper aims to standardize the application of the original CDC and Kansas case definitions by defining a framework for writing reliable code for complex case definitions, implementing this framework on a sample of 1343 Gulf War Veterans (GWVs), and validating the framework by applying the code to a sample of 41,077 GWVs. Main methods Methods were drawn from software engineering: write pseudocode, write test cases, and write code; then test code. Code was examined for accuracy, flexibility, replicability, and reusability. Key findings The pseudocode promoted understanding of the planned algorithm, encouraging discussion and leading to agreement on the case definition algorithms among all team members. The completed SAS code was written for and tested in the Gulf War Era Cohort and Biorepository (GWECB)4. This code was adapted and tested in the Million Veteran Program (MVP)5. The code was documented for reproducibility and reusability. Significance Ease of reuse suggests that this method could be used to standardize the application of other case definitions, reducing time and resources spent by each study team. Documentation, code, and test cases are available through the Department of Veterans Affairs (VA) Phenomics catalog6.

Colorectal cancer (CRC) screening guidelines recommend frequent colonoscopies and consideration of genetic testing in individuals with ≥10 cumulative adenomas. However, it is unclear how these guidelines apply to routine practice.We estimated the proportion of participants found to have ≥10 cumulative adenomas in a screening population and described their outcomes of advanced neoplasia (AN), CRC, and extra-colonic malignancy.We performed a secondary analysis of VA CSP#380, which includes 3121 veterans aged 50-75 who were followed up to 10 years after screening colonoscopy. We calculated the cumulative risk of ≥10 cumulative adenomas by Kaplan-Meier method. We compared baseline risk factors in those with and without ≥10 cumulative adenomas as well as the risk for AN (adenoma ≥1 cm, villous adenoma or high-grade dysplasia, or CRC) and extra-colonic malignancy by multivariate logistic regression.The cumulative risk of ≥10 cumulative adenomas over 10.5 years was 6.51% (95% CI 4.38%-9.62%). Age 60-69 or 70-75 at baseline colonoscopy was the only factors associated with the finding of ≥10 cumulative adenomas. Compared to those with 0-9 cumulative adenomas, participants with ≥10 cumulative adenomas were more likely to have had AN (OR 17.03; 95% CI 9.41-30.84), including CRC (OR 7.00; 95% CI 2.84-17.28), but not extra-colonic malignancies.Approximately 6.5% of participants in this screening population were found to have ≥10 cumulative adenomas over 10.5 years, which was uncommon before age 60. These participants were found to have AN and CRC significantly more often compared to those with lower cumulative adenomas.

Background Transportation barriers limit access to cancer care services and contribute to suboptimal clinical outcomes. Our objectives were to describe the frequency of Veterans reporting and the factors associated with transportation barriers to or from colorectal cancer (CRC) care visits. Methods Between November 2015 and September 2016, Veterans with incident stage I, II, or III CRC completed a mailed survey to assess perceived barriers to recommended care. Participants who reported difficulty with transportation to or from CRC care appointments were categorized as experiencing transportation barriers. We assessed pairwise correlations between transportation barriers, transportation-related factors (e.g., mode of travel), and chaotic lifestyle (e.g., predictability of schedules), and used logistic regression to examine the association between the reporting of transportation difficulties, distance traveled to the nearest Veterans Affairs (VA) facility, and life chaos. Results Of the 115 Veterans included in this analysis, 18% reported experiencing transportation barriers. Distance to the VA was not strongly correlated with the reporting of transportation barriers (Spearman’s ρ = 0.12, p = 0.19), but chaotic lifestyle was both positively and significantly correlated with experiencing transportation barriers (Spearman’s ρ = 0.22, p = 0.02). Results from the logistic regression model modestly supported the findings from the pairwise correlations, but were not statistically significant. Conclusions Transportation is an important barrier to or from CRC care visits, especially among Veterans who experience greater life chaos. Identifying Veterans who experience chaotic lifestyles would allow for timely engagement in behavioral interventions (e.g., organizational skills training) and with support services (e.g., patient navigation).

Background: The genetic basis for most individuals with high cumulative lifetime colonic adenomas is unknown. We investigated associations between known colorectal cancer–risk single-nucleotide polymorphisms (SNP) and increasing cumulative adenoma counts. Methods: The Cooperative Studies Program #380 screening colonoscopy cohort includes 612 selected participants age 50 to 75 with genotyped blood samples and 10 years of clinical follow-up. We evaluated 41 published “colorectal cancer–risk SNPs” for associations with individual cumulative adenoma counts or having ≥10 cumulative adenomas. SNPs were analyzed singly or combined in a polygenic risk score (PRS). The PRS was constructed from eight published SNPs associated with multiple adenomas, termed “adenoma-risk SNPs.” Results: Four colorectal cancer–risk SNPs were associated with increasing cumulative adenoma counts (P < 0.05): rs12241008 (gene: VTI1A), rs2423279 (BMP2/HAO1), rs3184504 (SH2B3), and rs961253 (FERMT1/BMP2), with risk allele risk ratios of 1.31, 1.29, 1.24, and 1.23, respectively. Three colorectal cancer–risk SNPs were associated with ≥10 cumulative adenomas (P < 0.05), with risk allele odds ratios of 2.09 (rs3184504), 2.30 (rs961253), and 1.94 (rs3217901). A weighted PRS comprised of adenoma-risk SNPs was associated with higher cumulative adenomas (weighted rate ratio = 1.57; P = 0.03). Conclusions: In this mostly male veteran colorectal cancer screening cohort, several known colorectal cancer–risk SNPs were associated with increasing cumulative adenoma counts and the finding of ≥10 cumulative adenomas. In addition, an increasing burden of adenoma-risk SNPs, measured by a weighted PRS, was associated with higher cumulative adenomas. Impact: Future work will seek to validate these findings in different populations and then augment current colorectal cancer risk prediction tools with precancerous, adenoma genetic data.

Background: Colorectal cancer (CRC) is the second most common cancer in Brazil. The Barretos Cancer Hospital (BCH) implemented a Fecal immunochemical test-based (FIT)-CRC screening program. Risk factors of the screening population and the prevalence of baseline colorectal neoplasia are important features for guiding a CRC screening strategy. This study aims to measure screening outcomes of the BCH program and associate with sociodemographic risk factors and genetic ancestry. Methods: This cross-sectional analysis included consecutive subjects between 50 and 65 years from the BCH (first round) CRC screening program. A REDCap database was built to track participants and measure clinical outcomes (adenoma, advanced adenoma (AA), and cancer). The ancestry components were analyzed using a multiplex PCR of 46 ancestry informative markers, based on insertion-deletion polymorphisms. A binary logistic regression model was used to examine the associations between sociodemographic factors and screening outcomes. Results: From Nov 2017 to Mar 2020, 2946 asymptomatic individuals were enrolled, being 83.0% females with a mean age of 57.1 ± 4.5 years, mainly from São Paulo State (79.1%). Self-reported skin color revealed 56.8% white, 36.6% brown, 5.8% black, and 0.7% yellow, and 69.9% had less than a high school diploma. The genetic ancestry revealed a mean proportion of 67.9% for European ancestry, 17.0% for African, 7.3% for East Asian, and 7.8% for Native American. A significant association was found between genetic ancestry proportions and self-reported skin colors (p 25kg/m². Of the 2946 participants, 80.7% completed and returned FIT kits. The inadequate FIT rate was 2.0%, and the positivity rate was 6.2%. The follow-up colonoscopy compliance rate was 90.5%, and the cecal intubation was successful in 99.0%. The PPV was 64.1% (86/134) for adenoma 20.1% (27/134) for AA, and 3.7% (5/134) for CRC. The five cancer patients had stage I (40.0%) or II (60.0%). The male gender (OR=2.94, 95% CI 1.06-8.17), BMI > 25kg/m² ≤ 30kg/m² (OR=5.40, 95% CI 1.42-20.52), alcohol consumption (OR=3.86, 95% CI 1.38-10.78), fried foods' consumption (OR=2.82, 95% CI 1.02-7.78) were associated to AA. Non-white skin color (OR=2.83, 95% CI 1.11-7.17), BMI > 25kg/m² ≤ 30kg/m² (OR=3.54, 95% CI 1.21-10.30), and eggs/milk consumption (OR=5.25, 95% CI 1.32-20.80) were associated to early adenoma. No association was found between genetic ancestry and screening outcomes. Conclusions: CRC detected in early stages corroborates the role of screening programs to increase the rate of early diagnosis. Further, lifestyle risk factors linked to colorectal cancer were significantly associated with the presence of a high and low-risk colorectal precursor lesion. Overall, our results in an admixed population can contribute to delineating preventive strategies and a targeted CRC screening program to improve CRC prevention and control in Brazil. Citation Format: Jun Porto, Adeylson G. Ribeiro, Lucas Henrique Viza, Laura W. Musselwhite, Thais Talarico, Maraisa Costa, Denise C. Rocha, Marco Antonio Oliveira, Jose Humberto T.G. Fregnani, Edmundo Mauad, Rui M. Reis, Dawn Provenzale, Denise P. Guimaraes. The impact of genetic ancestry and lifestyle factors on the risk of colorectal adenoma and adenocarcinoma in a Brazilian screening population [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-259.

Aims Many veterans of the 1990–1991 Gulf War Era (GWE) have experienced poorly understood health issues. In response to challenges recruiting this population for research, we conducted focus groups and semi-structured phone interviews with GWE veterans and subject matter experts (SMEs) to explore GWE veterans' perceptions about research. Main methods Transcribed discussions were content-analyzed. Participants discussed research-related motivators and barriers identified among other populations, and nuances that may be specific to GWE veterans. Key findings Examples of motivating factors included: seeking answers about causes of and treatment for health issues; helping oneself; and helping other veterans. Examples of barriers included: distrust and dissatisfaction with federal entities; lack of research follow-through; and concerns about privacy and confidentiality. Significance Researchers can use this information to better address GWE veterans' concerns and motivate them to participate in research. Inclusion of GWE veterans in research will allow researchers and clinicians to better understand and address health issues affecting this population.

The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provide recommendations for the management of patients with high-risk syndromes associated with an increased risk of colorectal cancer (CRC). The NCCN Panel for Genetic/Familial High-Risk Assessment: Colorectal meets at least annually to assess comments from reviewers within their institutions, examine relevant data, and reevaluate and update their recommendations. These NCCN Guidelines Insights focus on genes newly associated with CRC risk on multigene panels, the associated evidence, and currently recommended management strategies.

Colonoscopy vs. Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM): Rationale for Study Design

Aims This study characterizes Gulf War Illness (GWI) among U.S. veterans who participated in the Gulf War Era Cohort and Biorepository (GWECB). Main methods Mailed questionnaires were collected between 2014 and 2016. Self-reported GWI symptoms, symptom domain criteria, exclusionary diagnoses, and case status were examined based on the originally published Kansas and Centers for Disease Control (CDC) definitions in the GWECB cohort (n = 849 deployed to Gulf and n = 267 non-deployed). Associations among GWI and deployment status, demographic, and military service characteristics were examined using logistic regression. Key findings Among deployed veterans in our sample, 39.9% met the Kansas criteria and 84.2% met the CDC criteria for GWI. Relative to non-deployed veterans, deployed veterans had a higher odds of meeting four GWI case status-related measures including the Kansas symptom criteria (aOR = 2.05, 95% CI = 1.50, 2.80), Kansas GWI case status (aOR = 1.42, 95% CI = 1.05, 1.93), the CDC GWI case status (aOR = 1.57, 95% CI = 1.07, 2.29) and the CDC severe criteria (aOR = 2.67, 95% CI = 1.79, 3.99). Forty percent met the Kansas exclusionary criteria, with no difference by deployment status. Some symptoms were nearly universally endorsed. Significance This analysis provides evidence of a sustained, multisymptom illness in veterans who deployed to the Persian Gulf War compared to non-deployed Gulf War era veterans nearly 25 years later. Differences in symptoms attributed to GWI by deployment status have diminished since initial reports, suggesting the need to update GWI definitions to account for aging-related conditions and symptoms. This study provides a foundation for future efforts to establish a single GWI case definition and analyses that employ the biorepository.

Introduction: Nearly 50,000 incident cancer cases are reported in Veterans Affairs (VA) Central Cancer Registry (VACCR) annually. This article provides an updated report of cancer incidence recorded in VACCR. Materials and Methods: Data were obtained from VACCR for incident cancers diagnosed in the VA health care system, focusing on 2010 data. Cancer incidence among VA patients is described by anatomical site, sex, race, stage, and geographic location, and was compared to the general U.S. cancer population. Results: In 2010, among 46,170 invasive cancers, 97% were diagnosed among men. Approximately 80% of newly diagnosed patients were white, 19% black, and less than 2% were other minority races. Median age at diagnosis was 65 years. The three most frequently diagnosed cancers among VA were prostate (29%), lung/bronchus (18%), and colon/rectum (8%). Melanoma and kidney/renal pelvis tied for fourth (4%), and urinary bladder tied for sixth with liver and intrahepatic bile duct (3.4%). Approximately ...

Colorectal cancer (CRC) is a deadly but largely preventable disease. Screening improves outcomes, but screening rates vary across healthcare coverage models. In the Veterans Health Administration (VA), screening rates are high; however, it is unknown how CRC screening rates compare for Veterans with other types of healthcare coverage. To determine whether Veterans with Veteran-status-related coverage (VA, military, TRICARE) have higher rates of CRC screening than Veterans with alternate sources of healthcare coverage. We conducted a cross-sectional analysis of Veterans 50–75 years from the 2014 Behavioral Risk Factor Surveillance System survey. We examined CRC screening rates and screening modalities. We performed multivariable logistic regression to identify the role of coverage type, demographics, and clinical factors on screening status. The cohort included 22,138 Veterans. Of these, 76.7% reported up-to-date screening. Colonoscopy was the most common screening modality (83.7%). Screening rates were highest among Veterans with Veteran-status-related coverage (82.3%), as was stool-based screening (10.8%). The adjusted odds of up-to-date screening among Veterans with Veteran-status-related coverage were 83% higher than among Veterans with private coverage (adjusted OR = 1.83, 95% CI = 1.52–2.22). Additional predictors of screening included older age, black race, high income, access to medical care, frequent medical visits, and employed or married status. CRC screening rates were highest among Veterans with Veteran-status-related coverage. High CRC screening rates among US Veterans may be related to system-level characteristics of VA and military care. Insight to these system-level characteristics may inform mechanisms to improve CRC screening in non-VA settings.

Heartburn that persists despite proton-pump inhibitor (PPI) treatment is a frequent clinical problem with multiple potential causes. Treatments for PPI-refractory heartburn are of unproven efficacy and focus on controlling gastroesophageal reflux with reflux-reducing medication (e.g., baclofen) or antireflux surgery or on dampening visceral hypersensitivity with neuromodulators (e.g., desipramine).Patients who were referred to Veterans Affairs (VA) gastroenterology clinics for PPI-refractory heartburn received 20 mg of omeprazole twice daily for 2 weeks, and those with persistent heartburn underwent endoscopy, esophageal biopsy, esophageal manometry, and multichannel intraluminal impedance-pH monitoring. If patients were found to have reflux-related heartburn, we randomly assigned them to receive surgical treatment (laparoscopic Nissen fundoplication), active medical treatment (omeprazole plus baclofen, with desipramine added depending on symptoms), or control medical treatment (omeprazole plus placebo). The primary outcome was treatment success, defined as a decrease of 50% or more in the Gastroesophageal Reflux Disease (GERD)-Health Related Quality of Life score (range, 0 to 50, with higher scores indicating worse symptoms) at 1 year.A total of 366 patients (mean age, 48.5 years; 280 men) were enrolled. Prerandomization procedures excluded 288 patients: 42 had relief of their heartburn during the 2-week omeprazole trial, 70 did not complete trial procedures, 54 were excluded for other reasons, 23 had non-GERD esophageal disorders, and 99 had functional heartburn (not due to GERD or other histopathologic, motility, or structural abnormality). The remaining 78 patients underwent randomization. The incidence of treatment success with surgery (18 of 27 patients, 67%) was significantly superior to that with active medical treatment (7 of 25 patients, 28%; P = 0.007) or control medical treatment (3 of 26 patients, 12%; P0.001). The difference in the incidence of treatment success between the active medical group and the control medical group was 16 percentage points (95% confidence interval, -5 to 38; P = 0.17).Among patients referred to VA gastroenterology clinics for PPI-refractory heartburn, systematic workup revealed truly PPI-refractory and reflux-related heartburn in a minority of patients. For that highly selected subgroup, surgery was superior to medical treatment. (Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT01265550.).

Background Colorectal cancer is the fourth most commonly diagnosed cancer in the United States. Approximately 3–10% of the population has an increased risk for colorectal cancer due to family history and warrants more frequent or intensive screening. Yet, Methods In this ongoing randomized controlled trial, primary care providers at the Durham Veterans Affairs Health Care System and the Madison VA Medical Center are randomized to immediate intervention or wait-list control. Veterans are eligible if assigned to enrolled providers, have an upcoming primary care appointment, and have no conditions that would place them at increased risk for colorectal cancer (such as personal history, adenomatous polyps, or inflammatory bowel disease). Those with a recent lower endoscopy (e.g. colonoscopy, sigmoidoscopy) are excluded. Immediate intervention patients put their family health history information into a web-based platform, MeTree, which provides both patient- and provider-facing decision support reports. Wait-list control patients access MeTree 12 months post-consent. The primary outcome is the risk-concordant colorectal cancer screening referral rate obtained via chart review. Secondary outcomes include patient completion of risk management recommendations (e.g. colonoscopy) and referral for genetic consultation. We will also conduct an economic analysis and an assessment of providers’ experience with MeTree clinical decision support recommendations to inform future implementation efforts if the intervention is found to be effective. Discussion This trial will assess the feasibility and effectiveness of patient-collected family health history linked to decision support to promote risk-appropriate screening in a large healthcare system such as the Department of Veterans Affairs. Trial registration ClinicalTrials.gov, NCT02247336. Registered on 25 September 2014.

Colorectal cancer (CRC) is a common but largely preventable malignancy. Screening is recommended for all adults aged 50-75 years; however, screening rates are low nationally and vary by patient factors and across health care systems. It is currently unknown whether there are inequities in CRC screening rates by patient sociodemographic and/or clinical factors in the Veterans Health Administration (VA) where the majority of patients are CRC screening-eligible age and CRC is the third most commonly diagnosed cancer.We performed a retrospective cohort study using VA national clinical performance and quality data to determine the overall CRC screening rate, rates by patient sociodemographic and clinical factors, and predictors of screening adjusting for patient and system factors. We also determined whether disparities in screening exist in VA.The overall CRC screening rate in VA was 81.5%. Screening rates were lowest among American Indians/Alaska Natives [75.3%; adjusted odds ratio (aOR)=0.77, 95% confidence interval (CI)=0.65-0.90], those with serious mental illness (75.8%; aOR=0.65, 95% CI=0.61-0.69), those with substance abuse (76.9%; aOR=0.76, 95% CI=0.72-0.80), and those in the lowest socioeconomic status quintile (79.5%; aOR=1.10-1.31 for quintiles 2-5 vs. lowest quintile 1). Increasing age, Hispanic ethnicity, black race, Asian race, and high comorbidity were significant predictors of screening uptake.Many racial/ethnic disparities in CRC screening documented in non-VA settings do not exist in VA. Nonetheless, overall high VA CRC screening rates have not reached American Indians/Alaska Natives, low socioeconomic status groups, and those with mental illness and substance abuse. These groups might benefit from additional targeted efforts to increase screening uptake.

OBJECTIVE: The 1990–1991 Gulf War employed more women servicemembers than any prior conflict. Gender-based differences among veterans of this era have yet to be explored. This study is among the first and most recent to stratify Gulf War veteran demographics, lifestyle factors, and self-reported diagnoses by gender. METHODS: Data from the cross-sectional Gulf War Era Cohort and Biorepository pilot study (n = 1,318; collected between 2014 and 2016), including users and nonusers of the Veterans Health Administration, were used to calculate demographics and adjusted odds ratios. RESULTS: Women veterans were oversampled and comprised approximately 23% of the sample. Women reported similar rates of Veterans Health Administration use (44%) and deployment (67%) as men (46% and 72%, respectively). Women were less likely than men to report frequent alcohol use (adjusted odds ratio [aOR], 0.59; 95% confidence interval [CI], 0.43–0.81; p = .0009) or have a history of smoking (aOR, 0.65; 95% CI, 0.49–0.84; p = .0014). Among common health conditions, women were more likely than men to report a diagnosis of osteoporosis (aOR, 4.24; 95% CI, 2.39–7.51; p < .0001), bipolar disorder (aOR, 2.15; 95% CI, 1.15–4.04; p = .0167), depression (aOR, 2.39; 95% CI, 1.81–3.16; p < .0001), irritable bowel syndrome (aOR, 2.10; 95% CI, 1.43–3.09; p = .0002), migraines (aOR, 2.96; 95% CI, 2.18–4.01; p < .0001), asthma (aOR, 1.86; 95% CI, 1.29–2.67; p = .0008), and thyroid problems (aOR, 4.60; 95% CI, 3.14–6.73; p < .0001). Women were less likely than men to report hypertension (aOR, 0.55; 95% CI, 0.41–0.72; p < .0001), tinnitus (aOR, 0.46; 95% CI, 0.33–0.63; p < .0001), and diabetes (aOR, 0.44; 95% CI, 0.28–0.69; p = .0003). CONCLUSIONS: Health differences exist between female and male veterans from the 1990–1991 Gulf War. Gender-specific analyses are needed to better understand the unique health care needs of Gulf War Era veterans and direct future research.

Background & aimsColorectal cancer (CRC) incidence and mortality are increasing among persons younger than 50 years old in the United States, but risk factors associated with early-onset CRC (EOCRC) have not been widely studied.MethodsWe conducted a case-control study of US veterans 18 to 49 years old who underwent colonoscopy examinations from 1999 through 2014. EOCRC cases were identified from a national cancer registry; veterans who were free of CRC at their baseline colonoscopy through 3 years of follow-up were identified as controls. We collected data on age, sex, race/ethnicity, body weight, body mass index (BMI), diabetes, smoking status, and aspirin use. Multivariate-adjusted EOCRC odds were estimated for each factor, with corresponding 95% confidence interval (CI) values.ResultsOur final analysis included 651 EOCRC cases and 67,416 controls. Median age was 45.3 years, and 82.3% were male. Higher proportions of cases were older, male, current smokers, nonaspirin users, and had lower BMIs, compared with controls (P < .05). In adjusted analyses, increasing age and male sex were significantly associated with increased risk of EOCRC, whereas aspirin use and being overweight or obese (relative to normal BMI) were significantly associated with decreased odds of EOCRC. In post hoc analyses, weight loss of 5 kg or more within the 5-year period preceding colonoscopy was associated with higher odds of EOCRC (odds ratio 2.23; 95% CI 1.76-2.83).ConclusionsIn a case-control study of veterans, we found increasing age and male sex to be significantly associated with increased risk of EOCRC, and aspirin use to be significantly associated with decreased risk; these factors also affect risk for CRC onset after age 50. Weight loss may be an early clinical sign of EOCRC. More intense efforts are required to identify the factors that cause EOCRC and signs that can be used to identify individuals at highest risk.

Introduction: Colorectal cancer (CRC) accounts for approximately 8% of annual cancer cases in the Veterans Health Administration. While CRC incidence is decreasing, evidence suggests that the incidence among the subset of patients diagnosed before the age of 50 is increasing. The purpose of this work is to compare the clinical and demographic characteristics of veterans with early-onset CRC (age at diagnosis Methods: We conducted a retrospective analysis of national cohort data in the Veterans Affairs Central Cancer Registry on patients diagnosed with CRC between 2001 and 2011. Descriptive statistics (frequencies, medians) were used to compare characteristics among EOC and LOC patients and evaluate black-white differences within both groups of CRC patients. Results: In this cohort of 31,435 patients, 3% (N=966) had EOC, and this proportion was consistent each year. Statistically significant differences between EOC and LOC were noted for race, stage, and tumor location (all p Conclusion: Although we did not find an increasing proportion of EOC over time, EOC was more common in blacks than whites and more common in the distal large bowel. EOC in blacks, however, was more commonly proximal, had less advanced stage at diagnosis but similar survival compared to whites. EOC has distinct clinical characteristics in blacks that may reflect differences in molecular etiology. Our findings emphasize the importance of distinguishing between EOC and LOC to better understand the unique characteristics of early-onset disease and how they might inform prevention and early detection efforts. This abstract is also being presented as Poster C116. Citation Format: Monalesia Chapman, Christina D. Williams, Thomas Ivey Redding, Robin Bartlett, Neeta Chawla, Dawn Provenzale, Michael J. Kelley. Racial differences in characteristics of early- vs. late-onset colorectal cancer among veterans [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr PR11.

Background & Aims Few studies have evaluated long-term outcomes of ongoing colonoscopic screening and surveillance in a screening population. We aimed to determine the 10-year risk for advanced neoplasia (defined as adenomas ≥10mm, adenomas with villous histology or high-grade dysplasia, or colorectal cancer [CRC]) and assessed whether baseline colonoscopy findings were associated with long-term outcomes. Methods We collected data from the Department of Veterans Affairs Cooperative Studies Program Study on 3121 asymptomatic veterans (50–75 years old) who underwent a screening colonoscopy from 1994 through 1997 at 13 medical centers and were then followed for 10 years or until death. We included 1915 subjects with at least 1 surveillance colonoscopy and estimated cumulative incidence of advanced neoplasia by Kaplan-Meier curves. We then fit a longitudinal joint model to estimate risk of advanced neoplasia at each subsequent examination after baseline, adjusting for multiple colonoscopies within individuals. Results Through 10 years of follow-up, there were 146 individuals among all baseline colonoscopy groups found to have at least 1 incident advanced neoplasia. The cumulative 10-year incidence of advanced neoplasia was highest among those with baseline CRC (43.7%; 95% CI 13.0%–74.4%), followed by those with baseline advanced adenoma (AA) (21.9%; 95% CI 15.7–28.1). The cumulative 10-year incidence of advanced neoplasia was 6.3% (95% CI 4.1%–8.5%) and 4.1% (95% CI 2.7%–5.4%) for baseline 1 to 2 small adenomas ( Conclusions Baseline screening colonoscopy findings associate with advanced neoplasia within 10 years. Individuals with only 1 or 2 small adenomas at baseline have a low risk of advanced neoplasia over 10 years. Alternative surveillance strategies, could be considered for these individuals.

Background & Aims Post-colonoscopy colorectal cancers (PCCRCs) may arise from missed lesions or due to molecular features of tumors that allow them to grow rapidly. We aimed to compare clinical, pathology, and molecular features of PCCRCs (those detected within 6–60 months of colonoscopy) and detected CRCs (those detected within 6 months of a colonoscopy). Methods Within a population-based cross-sectional study of incident CRC cases in Utah (from 1995 through 2009), we identified PCCRCs (those cancers that developed within 5 years of a colonoscopy) and matched the patients by age, sex, and hospital site to patients with detected CRC. Archived specimens were retrieved and tested for microsatellite instability (MSI), CpG island methylation, and mutations in KRAS and BRAF. There were 2659 cases of CRC diagnosed within the study window; 6% of these (n = 159) were defined as PCCRCs; 84 of these cases had tissue available and were matched to 84 subjects with detected CRC. Results Higher proportions of PCCRCs than detected CRCs formed in the proximal colon (64% vs 44%; P = .016) and were of an early stage (86% vs 69%; P = .040). MSI was observed in 32% of PCCRCs compared with 13% of detected CRCs (P = .005). The other molecular features were found in similar proportions of PCCRCs and detected CRCs. In a multivariable logistic regression, MSI (odds ratio, 4.20; 95% CI, 1.58–11.14) was associated with PCCRC. There was no difference in 5-year survival between patients with PCCRCs vs detected CRCs. Conclusion In this population-based cross-sectional study of incident CRC cases in Utah, we found PCCRCs to be more likely to arise in the proximal colon and demonstrate MSI, so PCCRCs and detected CRC appear to have different features or processes of tumorigenesis. Additional studies are needed to determine if post-colonoscopy cancers arise through a specific genetic pathway.

The NCCN Guidelines for Colorectal Cancer (CRC) Screening outline various screening modalities as well as recommended screening strategies for individuals at average or increased-risk of developing sporadic CRC. The NCCN panel meets at least annually to review comments from reviewers within their institutions, examine relevant data, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize 2018 updates to the NCCN Guidelines, with a primary focus on modalities used to screen individuals at average-risk for CRC.