Cancer Biomarkers and Big Data: A Planetary Science Approach.

Cancer biomarker research has become a data-intensive discipline requiring innovative approaches for data analysis that can combine traditional and data-driven methods. Significant leveraging can be done transferring methodologies and capabilities across scientific disciplines, such as planetary science and astronomy, each of which are grappling with and developing similar solutions for the analysis of massive scientific data.

Novel Common Genetic Susceptibility Loci for Colorectal Cancer.

BACKGROUND: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. METHODS: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. RESULTS: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. CONCLUSIONS: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.

Inflammatory Bowel Diseases Can Adversely Impact Domains of Sexual Function Such as Satisfaction with Sex Life.

BACKGROUND: Aspects of sexual health, which can be adversely affected by chronic disease, have been inadequately explored in inflammatory bowel disease (IBD). AIMS: We evaluated patient-reported interest in sexual activity and satisfaction with sex life in a large cohort of IBD patients. METHODS: We conducted a cross-sectional study within the Crohn's and Colitis Foundation Partners Internet cohort. Sequential participants completed a 6-question supplemental online survey to examine sexual interest and satisfaction using the Patient-Reported Outcome Measurement Information System® (PROMIS®) Sexual Function and Satisfaction measures. One-sample t tests were used to compare interest and satisfaction scores to general population norms. RESULTS: Among 2569 individuals, 1639 had Crohn's disease (CD), 930 had ulcerative colitis (UC) or indeterminate colitis, and 71% were women. Mean PROMIS scores for sexual interest were comparable to the general US population in men (CD: 49 and UC: 50 vs. population mean 50) and women (CD: 41 and UC: 40 vs. population mean 42). However, sexual satisfaction scores were lower than the US population in men (CD: 48 and UC: 48 vs. 51) and women (CD: 47 and UC: 46 vs. 49), p < 0.01 for both. Older age, disease activity, depression, anxiety, and pain were associated with lower interest and satisfaction and lowered IBD-specific quality of life. CONCLUSIONS: IBD patients in a large online survey had similar levels of sexual interest but decreased sexual satisfaction compared to the general population. Exploring these sexual health domains during clinical encounters can aid in improving IBD quality of life.

Prevalence and Impact of Inflammatory Bowel Disease-Irritable Bowel Syndrome on Patient-reported Outcomes in CCFA Partners.

BACKGROUND: Inflammatory bowel disease (IBD) patients with persistent symptoms despite no or minimal inflammation are frequently described as having an overlap of IBD and irritable bowel syndrome (IBD-IBS). Limited data are available on how IBS impacts the individual patient with IBD. In this study, we aimed to evaluate the prevalence of IBD-IBS and investigate its impact on patient-reported outcomes. METHOD: We performed a cross-sectional analysis within the CCFA Partners Study. Bivariate analyses and logistic regression models were used to investigate associations between IBD-IBS and various demographic, disease factors, and patient-reported outcomes including anxiety, depression, sleep disturbances, pain interference, and social satisfaction. RESULTS: Of the 6309 participants included, a total of 1279 (20%) reported a coexisting IBS diagnosis. The prevalence of IBD-IBS in this cohort was similar within disease subtypes. A diagnosis of IBD-IBS was associated with higher narcotic use compared with those with no IBS diagnosis for both Crohn's disease, 17% versus 11% (P < 0.001) and ulcerative colitis/indeterminate colitis, 9% versus 5% (P < 0.001). Quality of life, as measured by Short Inflammatory Bowel Disease Questionnaire (SIBDQ) was lower in patients with IBD-IBS compared with those without. IBD-IBS diagnosis was associated with anxiety, depression, fatigue, sleep disturbances, pain interference, and decreased social satisfaction. CONCLUSIONS: In this sample of patients with IBD, high prevalence of concomitant IBS diagnosis was observed. IBD-IBS diagnosis was associated with increased narcotic use and adverse patient-reported outcome. Appropriate diagnosis, treatment, and counseling may help improve the functional status of IBD-IBS patients and decrease narcotic use.

Variation in Care of Inflammatory Bowel Diseases Patients in Crohn's and Colitis Foundation of America Partners: Role of Gastroenterologist Practice Setting in Disease Outcomes and Quality Process Measures.

BACKGROUND: As variation in care has previously been linked to quality, we aimed to describe variations in inflammatory bowel diseases care by gastroenterology (GI) practice setting. METHODS: We performed a cross-sectional study within the Crohn's and Colitis Foundation of America Partners and used bivariate analyses to compare patient characteristics by GI practice setting (GI-academic [GIA], GI-private, or GI-other). Regression models were used to describe the effects of provider type on steroid use, disease activity, and the quality of life. RESULTS: The study included 12,083 patients with inflammatory bowel diseases (7576 with Crohn's disease [CD] and 4507 with ulcerative colitis [UC]). Nearly 95% reported visiting a GI provider annually. Also, CD patients seen by GIA were younger, better educated, used less 5-aminosalicylate agents, and had higher biologic and immunomodulator use (P < 0.001 for all). On multivariate analysis of CD patients, GIA used less steroids when compared with GI-private (odds ratio, 0.84; 95% confidence interval, 0.67-1.06) or GI-other (odds ratio, 0.66; 95% confidence interval, 0.49-0.89). GIA patients were more likely to be in remission, have flu vaccine, and have better quality of life. UC patients seen by GIA were younger, had more hospitalizations, and previous surgery (P < 0.001 for all). No differences existed for steroid use, remission, flu vaccine, or quality of life for UC care on bivariate or multivariate analyses. CONCLUSIONS: Significant variations in care patterns and quality measures exist for CD across GI provider types, without similar variation in UC care. Interventions to reduce variations in care could improve the quality of care in CD.

The Impact of Ostomy on Quality of Life and Functional Status of Crohn's Disease Patients.

BACKGROUND: The potential need for an ostomy is a main concern for patients with inflammatory bowel disease. We performed this study to evaluate the impact of a long-term ostomy (≥6 mo duration) on the functional status and specific patient-reported outcomes in a population of patients with Crohn's disease (CD). METHODS: We performed a cross-sectional analysis within the Crohn's and Colitis Foundation of America Partners cohort. Bivariate analyses and logistic regression models were used to investigate associations between ostomy and various demographic, disease factors, and patient-reported outcomes for health-related quality of life. RESULTS: A total of 402 CD patients with ostomy for a minimum duration of 6 months were compared with 4331 CD patients with no ostomy. Patients with ostomy were more likely to be in clinical remission compared with those without ostomy, 48.5% versus 31.3%, respectively. Having an ostomy did not impact the overall health-related quality of life and was not associated with anxiety, depression, sleep disturbances, or reduced sexual interest and satisfaction. However, the presence of ostomy was associated with reduced social role satisfaction in both patients with controlled and active disease. Additionally, in the subset of patients who did not achieve clinical remission, those with ostomy experienced greater pain interference (odds ratio, 1.63; 95% confidence interval, 1.12-2.35) and fatigue (odds ratio, 1.66; 95% confidence interval, 1.15-2.39). CONCLUSIONS: Ostomy is well tolerated in CD patients, particularly when clinical remission is achieved.

Medication Utilization and the Impact of Continued Corticosteroid Use on Patient-reported Outcomes in Older Patients with Inflammatory Bowel Disease.

BACKGROUND: Older individuals with inflammatory bowel disease (IBD) require ongoing medications. We aimed to describe (1) medication use in older and younger IBD patients and (2) medication associations with patient reported outcomes (PROs) in older patients. METHODS: We conducted cross-sectional and longitudinal analyses within CCFA Partners internet-based cohort of patients with self-reported IBD. We assessed medication use by disease sub-type and age. We used bivariate analyses to (1) compare medication use in older and younger patients and (2) determine associations between continued steroid use and patient reported outcomes in older patients. RESULTS: We included 5382 participants with IBD; 1004 were older (≥age 60). Older patients with Crohn's disease (CD) had lower antitumor necrosis factor alpha (anti-TNF) use at baseline (29.1% versus 44.3%, P < 0.001), comparable steroid use (16.0% versus 16.5%, P = 0.77), and higher aminosalicylate use (40.3% versus 33.9%, P = 0.003) versus younger patients. Older ulcerative colitis (UC) patients had similar anti-TNF use (16.0% versus 19.2%, P = 0.16), lower steroid use (9.6% versus 15.4%, P = 0.004), and higher aminosalicylate use (73.8% versus 68.2%, P = 0.04) at baseline. In longitudinal analyses, older CD patients had higher continued steroid use (11.6% versus 7.8%, P = 0.002); which was associated with worsened anxiety (P = 0.02), sleep (P = 0.01), and fatigue (P = 0.001) versus nonuse. Older CD patients on steroids, versus anti-TNF or immunomodulators, had increased depression (P = 0.04) and anxiety (P = 0.03). CONCLUSIONS: Medication utilization differs in older patients with IBD. Older CD patients have higher continued steroid use associated with worsened patient reported outcomes. As in younger IBD populations, continued steroid use should be limited in older patients.

Harnessing person-generated health data to accelerate patient-centered outcomes research: the Crohn's and Colitis Foundation of America PCORnet Patient Powered Research Network (CCFA Partners).

The Crohn's and Colitis Foundation of America Partners Patient-Powered Research Network (PPRN) seeks to advance and accelerate comparative effectiveness and translational research in inflammatory bowel diseases (IBDs). Our IBD-focused PCORnet PPRN has been designed to overcome the major obstacles that have limited patient-centered outcomes research in IBD by providing the technical infrastructure, patient governance, and patient-driven functionality needed to: 1) identify, prioritize, and undertake a patient-centered research agenda through sharing person-generated health data; 2) develop and test patient and provider-focused tools that utilize individual patient data to improve health behaviors and inform health care decisions and, ultimately, outcomes; and 3) rapidly disseminate new knowledge to patients, enabling them to improve their health. The Crohn's and Colitis Foundation of America Partners PPRN has fostered the development of a community of citizen scientists in IBD; created a portal that will recruit, retain, and engage members and encourage partnerships with external scientists; and produced an efficient infrastructure for identifying, screening, and contacting network members for participation in research.

Role of Nonsteroidal Anti-Inflammatory Drugs in Exacerbations of Inflammatory Bowel Disease.

GOALS: To determine the role of nonsteroidal anti-inflammatory drugs (NSAIDs) in activation of inflammatory bowel disease (IBD). BACKGROUND: NSAIDs may activate inflammatory pathways in IBD. STUDY: Crohn's and Colitis Foundation of American Partners is an ongoing cohort study of patients living with IBD. All data are self-reported using the internet. We identified a subcohort of participants whose disease activity, based on short Crohn's Disease Activity Index and simple clinical colitis activity index, indicated remission. Pattern of use of NSAIDs was measured at baseline, and disease activity assessment was performed 6 months later. We used multivariate binomial regression to determine effects of NSAIDs on disease activity. RESULTS: A total of 791 individuals in remission had baseline and follow-up data available for analysis. Of these, 247 Crohn's disease (CD) patients (43.2%) and 89 ulcerative colitis (UC) patients (40.6%) reported NSAID use. CD patients with NSAID use ≥5 times/month had greater risk of active disease at follow-up (23% vs. 15%, P=0.04); [adjusted risk ratio (RR), 1.65; 95% confidence interval (CI), 1.12-2.44). No effect was observed in patients with UC (22% vs. 21%, P=0.98; adjusted RR, 1.25; 95% CI, 0.81-1.92). Acetaminophen use was associated with active disease at follow-up in CD (adjusted RR, 1.72; 95% CI, 1.11-2.68). CONCLUSIONS: Regular (≥5 times/mo) NSAID and acetaminophen use were associated with active CD, but not UC. Less frequent NSAID use was not associated with active CD or UC. These findings indicate that regular NSAID use may increase CD activity, or that NSAID use may be a marker of a less robust remission; thus reflecting subclinical disease activity.

Validation of an internet-based cohort of inflammatory bowel disease (CCFA partners).

BACKGROUND: As traditional methods have become increasingly difficult, the Internet offers a mechanism for conducting survey research quickly and efficiently. However, the validity of this research depends on the ability of respondents to accurately report health status. We used a large Internet-based inflammatory bowel disease (IBD) cohort to validate self-reported IBD against physician reports. METHODS: Between June 22, 2012, and April 01, 2013, all participants of CCFA Partners (n = 6681) were invited to participate, and 450 were selected by random stratified sampling. We sent physicians a survey to confirm IBD diagnosis and characteristics. We used descriptive statistics to compare data. RESULTS: A total of 4423 participants (66%) indicated interest. Of 450 selected, 261 (58%) consented, and physician reports were obtained for 184 (71%). Physicians confirmed IBD status in 178 (97%) and type in 171 (97% of confirmed). The matching between patient and physician reports for Crohn's disease (CD) was 82% for disease location, 89% for the presence of perianal disease, and 46% for disease behavior. For ulcerative colitis (UC), disease location matched 54% of the time. Physician reports confirmed the status of ever having bowel surgery for 97% of CD and 94% for UC and confirmed current pouch or ostomy in 84% of CD and 81% of UC. CONCLUSIONS: Self-reported IBD in CCFA Partners is highly accurate, and participants are willing to release medical records for research. Self-reported phenotypic characteristics were less valid. The validity of IBD diagnoses among the participants of CCFA Partners supports the use of this cohort for patient-centered outcome research.

Risk factors for depression in the elderly inflammatory bowel disease population.

BACKGROUND AND AIMS: Little is known about depression in elderly individuals with inflammatory bowel diseases (IBD). We assessed the point prevalence of depression and determined associations with disease activity, quality of life, and medication adherence in elderly patients with IBD. METHODS: We identified elderly (≥ 65 years) individuals within Crohn's and Colitis Foundation of America Partners, an online IBD cohort. Individuals completed the short geriatric depression scale (GDS). We used bivariate statistics to determine whether demographic or disease-related factors, disease activity, quality of life or medication adherence was associated with depression. We used logistic regression to estimate independent effects of depression on medication adherence. RESULTS: A total of 359 elderly individuals with IBD completed the GDS. The mean age was 70.2 years (SD 4.7); mean disease duration was 25.6 years (SD 17.6), and 62.6% had Crohn's disease (CD). The point prevalence of depression was 22.6%. Lower education levels (p=0.001), higher corticosteroid use (<0.01) and lower exercise levels (<0.001) were associated with depression. For both CD and ulcerative colitis (UC), those with depression had increased disease activity (short Crohn's disease activity index 52.5 versus 29, p=0.005, and simple clinical colitis activity index 5 versus 2, p=0.003). Depressed patients had lower quality of life (short IBD questionnaire 4.6 versus 5.7, p<0.001). Depressed individuals had reduced medication adherence (adjusted OR 2.18; 95% CI 1.04-4.57). CONCLUSIONS: Depression is common in this geriatric IBD cohort. Depression is independently associated with reduced medication adherence. Recognition and treatment of depression in elderly patients with IBD could improve outcomes.

Baseline comorbidities in a skin cancer prevention trial in Bangladesh.

BACKGROUND: Epidemiologic research suggests that increased cancer risk due to chronic arsenic exposure persists for several decades even after the exposure has terminated. Observational studies suggest that antioxidants exert a protective effect on arsenical skin lesions and cancers among those chronically exposed to arsenic through drinking water. This study reports on the design, methods and baseline analyses from the Bangladesh Vitamin E and Selenium Trial (BEST), a population-based chemoprevention study conducted among adults in Bangladesh with visible arsenic toxicity. MATERIALS AND METHODS: Bangladesh Vitamin E and Selenium Trial is a 2 × 2 full factorial, double-blind, randomized controlled trial of 7000 adults having manifest arsenical skin lesions evaluating the efficacy of 6-year supplementation with alpha-tocopherol (100 mg daily) and L-selenomethionine (200 µg daily) for the prevention of nonmelanoma skin cancer. RESULTS: In cross-sectional analyses, we observed significant associations of skin lesion severity with male gender (female prevalence odds ratio (POR) = 0.87; 95% CI = 0.79-0.96), older age (aged 36-45 years, POR = 1.27; 95% CI = 1.13-1.42; aged 46-55 years, POR = 1.44; 95% CI = 1.27-1.64 and aged 56-65 years, POR = 1.50; 95% CI = 1.26-1.78 compared with aged 25-35 years), hypertension (POR = 1.29; 95% CI = 1.08-1.55), diabetes (POR = 2.13; 95% CI = 1.32-3.46), asthma (POR = 1.55; 95% CI = 1.03-2.32) and peptic ulcer disease (POR = 1.20; 95% CI = 1.07-1.35). CONCLUSIONS: We report novel associations between arsenical skin lesions with several common chronic diseases. With the rapidly increasing burden of preventable cancers in developing countries, efficient and feasible chemoprevention study designs and approaches, such as employed in BEST, may prove both timely and potentially beneficial in conceiving cancer chemoprevention trials in Bangladesh and beyond.

Patient perception of chronic illness care in a large inflammatory bowel disease cohort.

BACKGROUND: Improvements in care for inflammatory bowel diseases could use the Chronic Care Model, an evidence-based approach that has improved patient outcomes and reduced costs in other illnesses. Specific aims include (1) to explore patient perception of chronic illness care in a large inflammatory bowel disease cohort and (2) to determine whether demographic factors, medication adherence, quality of life, disease type, and activity were associated with perception of chronic illness care. METHODS: We randomly selected 1000 participants from the Crohn's and Colitis Foundation of America Partners Internet cohort to receive the validated Patient Assessment of Chronic Illness Care (PACIC) instrument, which measures patient experience with specific aspects of care congruent with the Chronic Care Model on a scale of 1 to 5, with 5 being highest perception of care. We used descriptive and bivariate statistics to assess relationships. RESULTS: Nine hundred and forty-five participants completed the PACIC (576 Crohn's disease, 339 ulcerative colitis, and 30 indeterminate or other; 74% female, mean age 45 [SD = 15.1], mean PACIC 2.4 [SD = 0.93]). Recent gastroenterologist visit, hospitalization, surgery, and current pouch/ostomy were all associated with significantly higher PACIC (P < 0.05). PACIC correlated positively with quality of life (Pearson's correlation = 0.12, P = 0.003) but not medication adherence or disease activity. CONCLUSIONS: Reports of chronic illness care in this inflammatory bowel disease cohort are in the same range as other illnesses. PACIC is positively associated with quality of life, so efforts to align care with the Chronic Care Model may benefit this population. Subjects who had more subspecialty interactions reported an increased perception of care, indicating the important role of direct patient contact.

Bioinformatics: biomarkers of early detection.

Capturing, sharing, and publishing cancer biomarker research data are all fundamental challenges of enabling new opportunities to research and understand scientific data. Informatics experts from the National Cancer Institute's (NCI) Early Detection Research Network (EDRN) have pioneered a principled informatics infrastructure to capture and disseminate data from biomarker validation studies, in effect, providing a national-scale, real-world successful example of how to address these challenges. EDRN is a distributed, collaborative network and it requires its infrastructure to support research across cancer research institutions and across their individual laboratories. The EDRN informatics infrastructure is also referred to as the EDRN Knowledge Environment, or EKE. EKE connects information about biomarkers, studies, specimens and resulting scientific data, allowing users to search, download and compare each of these disparate sources of cancer research information. EKE's data is enriched by providing annotations that describe the research results (biomarkers, protocols, studies) and that link the research results to the captured information within EDRN (raw instrument datasets, specimens, etc.). In addition EKE provides external links to public resources related to the research results and captured data. EKE has leveraged and reused data management software technologies originally developed for planetary and earth science research results and has infused those capabilities into biomarker research. This paper will describe the EDRN Knowledge Environment, its deployment to the EDRN enterprise, and how a number of these challenges have been addressed through the capture and curation of biomarker data results.