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Background: Intake of aspirin is associated with reduction in risk of colorectal adenoma and carcinoma. Some plants contain salicylates, and individuals not taking aspirin may have measurable salicylate levels. However, the association between serum salicylate level and recurrence of adenoma in nonusers of aspirin has not been studied. Methods: We measured serum salicylate levels in participants in a randomized controlled trial with calcium supplementation for the prevention of colorectal adenomas. Generalized linear models were used to assess the association between serum levels and adenoma risk during the follow-up period of the trial. Results: We did not find an association with recurrence of adenomas or advanced adenomas with serum salicylate levels at year 1 among nonusers of aspirin. There was no effect modification of the chemopreventive effect of calcium supplementation in reducing risk of recurrent adenomas or advanced adenomas. Conclusions: Among nonusers of ASA, serum salicylate levels are not associated with risk of recurrence of adenomas. Impact: Serum salicylate levels can be detected in individuals not taking aspirin, but the levels may be too low to confer protection from risk of recurrent adenomas. Cancer Epidemiol Biomarkers Prev; 20(4); 679–82. ©2011 AACR.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that affects nearly 500,000 Americans.1,2 The clinical course is typically relapsing and remitting: patients experience flares of their illness with symptoms of abdominal pain, diarrhea, rectal bleeding, and extra-intestinal manifestations, followed by periods of remission. Thus, the goals of therapy are twofold: 1) to treat disease flares (induction of remission) and 2) to prolong the length of time between flares (maintenance of remission). Despite the morbidity and mortality associated with UC,3 limited treatment options exist and additional therapeutic agents are needed. Thiazolidinediones, inhibitors of PPAR gamma,4 were introduced to the US market in 1997. Although currently indicated for the treatment of type 2 diabetes mellitus (“diabetes”),5 preclinical data and a recent randomized controlled trial have demonstrated the efficacy of rosiglitazone (one member of the thiazolidinedione class) for the induction of remission in UC patients with active disease.6–9 Yet the effectiveness of thiazolidinediones in the maintenance of UC remission has not been comprehensively evaluated. Diabetes is one of the most common chronic illnesses in the US, with a prevalence of 8%.10 Based on the combined prevalence of UC and diabetes, a substantial percentage of Americans may be affected by both conditions. UC may be particularly problematic in patients with coexisting diabetes because oral steroids, a mainstay of UC treatment, can exacerbate hyperglycemia. Therefore, preventing UC flares in these patients is of particular importance. Thiazolidinediones are considered second-line oral medications, reserved for diabetics who fail to achieve metabolic goals on metformin therapy. However, if thiazolidinediones are effective in maintaining UC remission in diabetic patients, there would be a strong argument to move this class to first-line therapy in diabetic patients with UC. Additionally, since few medications have been shown to maintain remission in UC, thiazolidinediones could have a role in the primary treatment of UC patients with or without diabetes. Therefore, we performed an exploratory retrospective cohort study using administrative data to examine the association between thiazolidinedione use and UC flares in patients with UC and diabetes.

To determine whether polyp detection rates are reduced as time progresses through half and full-day endoscopy shifts.Polyp detection on colonoscopy may be reduced during colonoscopies performed later in the day.Retrospective analysis of screening colonoscopies performed by attending physicians only between August 2003 and August 2005 at University of North Carolina Hospitals. The primary outcome was detection of any polyp. The secondary outcome was adenoma detection. Both were assessed by time of day and shift type.A total of 3421 eligible screening colonoscopies, performed by 20 attending gastroenterologists, were analyzed. Polyp detection rate for colonoscopies initiated before 9 AM was 48.6%, versus 34.0% for those initiated after 4:00 PM (P=0.04). On multivariate analysis, each hour of the day was associated with reduced odds of polyp detection [adjusted odds ratio (OR) 0.93, 95% confidence interval (CI) 0.89-0.98 for any polyp; adjusted OR: 0.94, 95% CI: 0.89-0.98 for adenoma]. When evaluated by physician shift, the odds of polyp detection were reduced in the last 1.5 hours compared with the first 1.5 hours of the shift, regardless of the length or timing of the shift (AM shift: OR: 0.63, 95% CI: 0.41-0.96; PM shift: OR: 0.79, 95% CI: 0.42-1.46; and full-day shift: OR: 0.67, 95% CI: 0.44-1.00).Polyp detection by attending tertiary-care gastrointestinal physicians is reduced as time progresses during both half and full-day endoscopy shifts. These findings have implications for future quality improvement interventions.

Background Recommendations for venous thromboembolism (VTE) prophylaxis in patients with inflammatory bowel disease (IBD) can be refined by incorporating patient-specific risk factors. Objectives To determine the risk of deep venous thrombosis (DVT) and pulmonary embolism (PE) in children and adults with Crohn's disease and ulcerative colitis and evaluate whether this risk varies by age and/or presence of other risk factors. Methods We performed a cohort study using Danish administrative data. Incidence rates of DVT and PE were calculated among patients with IBD and an age- and gender-matched comparison population and compared using Cox proportional hazards regression. We performed additional analyses stratifying by age, gender and disease type and restricting outcomes to unprovoked events (occurring without known malignancy, surgery, fracture/trauma or pregnancy). We next performed a nested case-control study to adjust for additional co-morbidities (congestive heart failure, diabetes, myocardial infarction and stroke) and the use of hormone replacement and antipsychotic medications. Results The study included 49 799 patients with IBD (14 211 Crohn's disease, 35 229 ulcerative colitis) and 477 504 members of the general population. VTE risk was elevated in patients with IBD (HR=2.0 (95% CI 1.8 to 2.1) for total events, HR=1.6 (95% CI 1.5 to 1.8) for unprovoked events). Although the incidence of VTE increased with age, the RR was higher in younger patients. Among those ≤20 years old, HRs were 6.0 (95% CI 2.5 to 14.7) for DVT and 6.4 (95% CI 2.0 to 20.3) for PE. After further adjusting for co-morbidity and medication use in the case-control analysis, ORs for all events remained in the 1.5-1.8 range. Discussion Patients with IBD have twice the incidence of PE or DVT as does the general population. This risk persisted after taking into account other VTE risk factors. Relative risks were particularly high at young ages, though actual incidence increased with age. These findings can further inform risk-benefit analysis of VTE prophylaxis.

Background: The inflammatory bowel diseases (IBDs) Crohn's disease (CD) and ulcerative colitis (UC) affect over 1 million people in the United States, yet little is known about healthcare utilization by affected individuals. The objectives were to describe the healthcare utilization associated with IBD in an insured U.S. population and to determine how sociodemographic factors impact healthcare utilization in this population. Methods: Using an administrative database comprised of 87 health plans, we ascertained cases of CD and UC using an administrative definition. We identified inpatient, office-based, emergency (ED), and endoscopy services occurring between 2003–2004 in IBD patients and matched controls. For each case, excess utilization was determined by subtracting the mean number of control visits from the number of case visits. Multivariate logistic and linear regressions were used to identify the sociodemographic factors associated with excess utilization. Results: We identified 9056 CD patients and 10,364 UC patients. The mean number of annual excess hospitalizations, ED visits, and office visits per 100 patients for CD were 21.7, 20.1, and 493, respectively. These values for UC were 13.3, 10.3, and 364, respectively. In general, utilization was higher in CD compared with UC, and in younger patients compared with older patients. Utilization also varied by gender, geographical region, and insurance type (Medicaid versus commercial). Conclusions: In the U.S., patients with IBD consume substantial healthcare resources. Resource utilization varies by patient age and disease type, and to a lesser extent, gender, geographical region, and insurance type. These findings may be used to inform health policy. (Inflamm Bowel Dis 2011;)

The increasing incidence of colorectal cancer in younger adults (aged

The original version of the article unfortunately contained an error in Results section of Abstract.

Lower incidence rates of distal large bowel cancer in women when compared with men support the protective role of female hormones. We aimed to determine the associations between hormone replacement therapy, oral contraceptive use, and distal large bowel cancer.We conducted a population-based case-control study of incident distal large bowel cancer in North Carolina between 2001 and 2006. Data on hormone replacement therapy, oral contraceptive use, demographics, and risk factors were obtained through in-person interviews. Odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between oral contraceptive use, hormone replacement therapy, and distal large bowel cancer were estimated through unconditional logistic regression models overall, by duration of use, and within strata of race.There were a total of 443 women with distal large bowel cancer and 405 controls. Ever use of hormone replacement therapy was strongly associated with a reduced risk of distal large bowel cancer (OR 0.52, 95% CI 0.38-0.72). Further reduction of distal large bowel cancer risk occurred with increased duration of use (4 years (OR 0.77, 95% CI 0.44-1.35), 4-8 years (OR 0.64, 95% CI 0.37-1.10), 9-14 years (OR 0.47, 95% CI 0.27-0.81), andor=15 years (OR 0.34, 95% CI 0.20-0.58)). Ever use of oral contraceptives was not associated with reduced incidence of distal large bowel cancer (OR 0.95, 95% CI 0.67-1.34) nor was duration of use. There were no differences by race.Hormone replacement therapy is associated with a lower risk of distal large bowel cancer. This risk is further reduced with increased duration of use. Hormone replacement therapy may be partially responsible for the reduced incidence of distal large bowel cancer in women compared with men.

Background & Aims Proton pump inhibitors (PPIs) are commonly used medications. Recent studies reported an increased risk of acute myocardial infarction (MI) in PPI users vs non-users. We evaluated MI risk associated with PPIs compared with histamine-2 receptor antagonists (H2RAs) in privately insured adults in the United States. Methods Using administrative claims from commercial and Medicare Supplemental plans (2001–2014), we compared risk of MI in patients who started a new prescription for PPIs vs H2RAs. Enrollees were followed from their first prescription until MI, medication discontinuation, plan disenrollment, or December 31, 2014. MI was defined using hospital diagnosis codes. Risk differences (RD), risk ratios, and 95% confidence intervals (CIs) were estimated using Kaplan-Meier methods at 3, 12, and 36 months after treatment initiation. Standardized morbidity ratio weights were used to control measured confounding. Analyses were stratified by plan type (commercial vs Medicare Supplemental). Results We identified more than 5 million new users of prescription PPIs and H2RAs. Median follow-up time was 60 days for patients with commercial insurance and 96 days in patients with Medicare Supplemental insurance. The 12-month weighted risk of MI was low overall (approximately 2 cases per 1000 among patients in commercial plans; 8 per 1000 among patients in Medicare Supplemental plans). In the RD analysis, we found no significant differences in MI risk between patients who started PPIs vs H2RAs for the first 12 months, either in the commercial population (weighted RD per 1000, –0.08; 95% CI, –0.51 to 0.36) or the Medicare Supplemental population (weighted RD per 1000, –0.45; 95% CI, –1.53 to 0.58). Conclusion In an analysis of administrative claims from commercial and Medicare Supplemental plans, we found no evidence that prescription PPIs increase risk of MI compared with prescription H2RAs. Physicians and patients should not avoid starting a PPI because of concerns related to MI risk.

The following is an edited reprint of the presidential address delivered by Robert S. Sandler, MD, MPH, AGAF, during the American Gastroenterological Association Plenary Session at Digestive Disease Week 2009.

Recently, the potential health effects of trans-fatty acid consumption have raised concerns. A few studies have examined the risk of colorectal cancer with increasing consumption of trans-fatty acids, but none investigated the risk of rectal cancer, which may have different risk factors than colon cancer. Our objective was to explore the relationship between trans-fatty acid consumption and distal colorectal (sigmoid, rectosigmoid, and rectal) cancer using a case-control study of Whites (n = 1,516) and African Americans (n = 392) in North Carolina from 2001 to 2006. Matched cases and controls were interviewed about demographic information, lifestyle factors, and diet. White cases reported higher mean consumption of trans-fatty acid than White controls, but mean consumption was similar for African American cases and controls. Relative to the lowest quartile, the highest quartiles of energy-adjusted trans-fatty acid consumption were positively associated with distal colorectal cancer for Whites [adjusted ORs for the third and fourth quartiles are 1.54 (95%CI: 1.12, 2.13) and 1.45 (95%CI: 1.04, 2.03), respectively]. Consumption was not associated with distal colorectal cancer in African Americans [adjusted ORs for the third and fourth quartiles are 0.98 (95%CI: 0.47, 2.05) and 0.87 (95%CI 0.42, 1.81), respectively]. In conclusion, high consumption of trans-fatty acids was positively associated with distal colorectal cancer among Whites.

The Aspirin/Folate Polyp Prevention Trial found that aspirin, but not folic acid, reduced recurrence of colorectal adenomas. This study examined whether treatment effects on inflammation markers explained the trial results. The trial had a factorial design with three aspirin (placebo, 81, and 325 mg/d) and two folic acid (placebo and 1 mg/d) groups. There were 884 subjects who had colonoscopic evaluation for adenomas at year 3 and plasma levels of C-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), soluble TNF receptor type II (sTNF-R2), and IL-1 receptor antagonist (IL-1Ra) measured at baseline and year 3. Among individuals not receiving folic acid, there was a 4% decrease (mean ratio of year 3 to baseline levels = 0.96, 95% confidence interval [CI] = 0.82 to 1.14) in CRP for a period of 3 years in the 325 mg of aspirin group vs a 20% increase (mean ratio = 1.20, 95% CI = 1.03 to 1.41) in the placebo group (P = .027). By contrast, the reverse was observed among individuals who also received folic acid (P(interaction) = .013). Changes in inflammation markers were not associated with adenoma recurrence. Low-dose aspirin (325 mg/d) is beneficial in stabilizing CRP levels, which may be abrogated by folate. Nevertheless, inflammation markers do not mediate the chemopreventive effect of aspirin on colorectal adenomas.

Cancer is a growing global health issue, and many countries are ill-prepared to deal with their current cancer burden let alone the increased burden looming on the horizon. Growing and aging populations are projected to result in dramatic increases in cancer cases and cancer deaths particularly in low- and middle-income countries. It is imperative that planning begin now to deal not only with those cancers already occurring but also with the larger numbers expected in the future. Unfortunately, such planning is hampered, because the magnitude of the burden of cancer in many countries is poorly understood owing to lack of surveillance and monitoring systems for cancer risk factors and for the documentation of cancer incidence, survival and mortality. Moreover, the human resources needed to fight cancer effectively are often limited or lacking. Cancer diagnosis and cancer care services are also inadequate in low-and middle-income countries. Late-stage presentation of cancers is very common in these settings resulting in less potential for cure and more need for symptom management. Palliative care services are grossly inadequate in low- and middle-income countries, and many cancer patients die unnecessarily painful deaths. Many of the challenges faced by low- and middle-income countries have been at least partially addressed by higher income countries. Experiences from around the world are reviewed to highlight the issues and showcase some possible solutions.

Disparities in incidence and mortality rates of colon cancer exist between Whites and African Americans. Prior studies examined the association between trans fatty acid consumption and colorectal cancer, but none assessed this possible relationship within a large study population of African Americans and Whites. Using data from a population-based, case-control study in North Carolina, we investigated this association with attention to possible racial differences. Cases and matched controls were queried on demographic characteristics, lifestyle factors, medical history, and diet. Cases reported higher daily consumption (g/day) of trans fatty acids (mean = 5.9, SD = 2.9, median = 5.5, IQR = 3.8-7.5) compared to controls (mean = 5.2, SD = 2.4, median = 4.7, IQR = 3.5-6.4). Energy-adjusted trans fatty acid consumption was not associated with colon cancer. Compared to participants in the lowest quartile of consumption, those in the highest quartile had an adjusted odds ratio of 1.01 (95% confidence interval 0.69, 1.49) for Whites and 0.99 (95% confidence interval 0.61, 1.62) for African Americans. No association was found between increased consumption of trans fatty acid and specific tumor location (proximal or distal colon). In conclusion, trans fatty acid consumption is not associated with colon cancer and does not contribute to disparities in colon cancer rates.

Phase II clinical trials of mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitors are ongoing and ERK1/2 activation is frequently used as a biomarker. In light of the mutational activation of BRAF and KRAS in colorectal cancer, inhibitors of the Raf-MEK-ERK mitogen-activated protein kinase are anticipated to be promising. Previous studies in pancreatic cancer have found little correlation between BRAF/KRAS mutation status and ERK1/2 activation, suggesting that identifying biomarkers of MEK inhibitor response may be more challenging than previously thought. The purpose of this study was to evaluate the effectiveness of MEK inhibitor therapy for colorectal cancer and BRAF/KRAS mutation status and ERK1/2 activation as biomarkers for MEK inhibitor therapy. First, we found that MEK inhibitor treatment impaired the anchorage-independent growth of nearly all KRAS/BRAF mutant, but not wild-type, colorectal cancer cells. There was a correlation between BRAF, but not KRAS, mutation status and ERK1/2 activation. Second, neither elevated ERK1/2 activation nor reduction of ERK1/2 activity correlated with MEK inhibition of anchorage-independent growth. Finally, we validated our cell line observations and found that ERK1/2 activation correlated with BRAF, but not KRAS, mutation status in 190 patient colorectal cancer tissues. Surprisingly, we also found that ERK activation was elevated in normal colonic epithelium, suggesting that normal cell toxicity may be a complication for colorectal cancer treatment. Our results suggest that although MEK inhibitors show promise in colorectal cancer, KRAS/BRAF mutation status, but not ERK activation as previously thought, may be useful biomarkers for MEK inhibitor sensitivity. [Mol Cancer Ther 2009;8(4):834–43]

Colorectal cancer and diabetes are common diseases that share many risk factors. It has been hypothesized that diabetes is a risk factor for colorectal cancer. We used two large population-based case-control studies from North Carolina to determine whether diabetes and/or insulin therapy was associated with colon cancer and/or rectal cancer (defined as cancer of the sigmoid colon, rectosigmoid, or rectum) and whether this association differed by race. Cases and matched controls from the North Carolina Colon Cancer Studies I and II were interviewed about demographics, dietary factors, diagnosis of diabetes, and use of medications to treat diabetes. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression. Colon and rectal cancer cases reported a higher prevalence of diabetes than their respective control groups. Compared with Whites without diabetes, Whites with diabetes had adjusted ORs of 1.40 (95% CI, 0.93-2.12) for colon cancer and 1.38 (95% CI, 1.00-1.90) for rectal cancer. Diabetes was not associated with colon or rectal cancer among African Americans [OR, 1.17 (95% CI, 0.81-1.70) and 0.75 (95% CI, 0.44-1.28), respectively]. Among Whites with diabetes, insulin use was positively associated with rectal cancer. The same association was not seen for African American diabetics using insulin; however, the number of African Americans using insulin was small. In sum, diabetes was positively associated with rectal cancer and approached a positive association with colon cancer among Whites. No association was present among African Americans. Insulin use was also positively associated with rectal cancer among Whites. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1239–42)

Background Multiple lines of evidence indicate that aspirin has an antineoplastic effect in the large bowel. Randomized clinical trials have been conducted to evaluate the effectiveness of aspirin for reducing the risk of colorectal adenomas. A meta-analysis of these trials will provide more precise estimates of the aspirin effect, both overall and in subgroups. Methods We combined data from all randomized double-blind placebo-controlled trials that evaluated aspirin for the prevention of colorectal adenomas. We used random-effects meta-analysis to estimate risk ratios and 95% confidence intervals (CIs) for the effect of aspirin on the occurrence of adenomas and of advanced lesions (ie, tubulovillous adenomas, villous adenomas, adenomas >or=1 cm in diameter, adenomas with high-grade dysplasia, or invasive cancer). All statistical tests were two-sided. Results We identified four clinical trials with 2967 randomly assigned participants. Each trial evaluated aspirin for the secondary prevention of colorectal adenomas. Doses of aspirin tested ranged from 81 to 325 mg/d. The average age of participants at baseline was 58 years, and 60% were male. Median follow-up was 33 months. A total of 2698 participants underwent colonoscopic follow-up and were included in the analysis of adenoma occurrence and advanced-lesion occurrence after randomization. Among these participants, adenomas were found in 424 (37%) of the 1156 participants allocated to placebo and in 507 (33%) of the 1542 participants allocated to any dose of aspirin. Advanced lesions were found in 12% of participants in the placebo group and in 9% of participants allocated to any dose of aspirin. The pooled risk ratio of any adenoma for any dose of aspirin vs placebo was 0.83 (95% CI = 0.72 to 0.96). This corresponded to an absolute risk reduction of 6.7% (95% CI = 3.2% to 10.2%). For any advanced lesion, the pooled risk ratio was 0.72 (95% CI = 0.57 to 0.90). We found no statistically significant effect modification for any of the baseline factors studied. Conclusion Aspirin is effective for the prevention of colorectal adenomas in individuals with a history of these lesions.

Background & Aims The effect of gastrointestinal endoscopy nursing experience on polyp detection is unknown. The aim of this study was to determine whether nurse experience is associated with odds of polyp detection. Methods We performed a retrospective analysis of screening colonoscopies performed by attendings at University of North Carolina hospitals between August 2003 and 2005. Nurse experience was dichotomized at 6 months. The primary outcome was polyp detection, with secondary analysis by histologic type. Descriptive statistics, bivariate analysis, and multiva-riable logistic regression were performed. Results Any polyp was detected in 44% of the eligible 3631 colonoscopies. Multiple polyps were detected in 23%, adenomas in 25%, advanced lesions in 5%, and hyperplastic polyps in 11%. Twenty-nine nurses were employed during the study period, 19 of whom were new to endoscopy nursing. For nurses with 6 months of experience or less, any polyp was detected in 40.3% of procedures compared with 46.0% of procedures for nurses with more than 6 months of experience (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.09–1.46). Similar results were seen for multiple polyps (OR, 1.54; 95% CI, 1.29–1.84) and hyperplastic polyps (OR, 1.47; 95% CI, 1.22–1.76), but not for adenomas (OR, 1.10; 95% CI, 0.93–1.30) or advanced lesions (OR, 0.99; 95% CI, 0.71–1.36). These relationships were unchanged after adjusting for potential confounding patient and procedure variables. Conclusions Procedures staffed by less-experienced gastrointestinal endoscopy nurses have increased odds of not detecting polyps. Subanalysis suggests that detection of hyperplastic polyps explains much of this relationship.

Diets high in red meat have been consistently associated with colorectal cancer (CRC) risk and may result in exposure to carcinogens that cause DNA damage [i.e polycyclic aromatic hydrocarbons, heterocyclic amines (HCAs) and N-nitroso compounds]. Using a family-based study, we investigated whether polymorphisms in the nucleotide excision repair (NER) (ERCC1 3′ untranslated region (UTR) G/T, XPD Asp312Asn and Lys751Gln, XPC intron 11 C/A, XPA 5′ UTR C/T, XPF Arg415Gln and XPG Asp1104His) and mismatch repair (MLH1 Ile219Val and MSH2 Gly322Asp) pathways modified the association with red meat and poultry intake. We tested for gene–environment interactions using case-only analyses (n = 577) and compared the results using case-unaffected sibling comparisons (n = 307 sibships). Increased risk of CRC was observed for intake of more than or equal to three servings per week of red meat [odds ratio (OR) = 1.8, 95% confidence interval (CI) = 1.3–2.5)] or high-temperature cooked red meat (OR = 1.6, 95% CI = 1.1–2.2). Intake of red meat heavily brown on the outside or inside increased CRC risk only among subjects who carried the XPD codon 751 Lys/Lys genotype (case-only interaction P = 0.006 and P = 0.001, respectively, for doneness outside or inside) or the XPD codon 312 Asp/Asp genotype (case-only interaction P = 0.090 and P < 0.001, respectively). These interactions were stronger for rectal cancer cases (heterogeneity test P = 0.002 for XPD Asp312Asn and P = 0.03 for XPD Lys751Gln) and remained statistically significant after accounting for multiple testing. Case-unaffected sibling analyses were generally supportive of the case-only results. These findings highlight the possible contribution of diets high in red meat to the formation of lesions that elicit the NER pathway, such as carcinogen-induced bulky adducts.

The evaluation of tumour molecular markers may be beneficial in prognosis and predictive in therapy. We develop a stopping rule approach to assist in the efficient utilisation of resources and samples involved in such evaluations. This approach has application in determining whether a specific molecular marker has sufficient variability to yield meaningful results after the evaluation of molecular markers in the first n patients in a study of sample size N (n/=N). We evaluated colorectal tumours for mutations (microsatellite instability, K-ras, B-raf, PI3 kinase, and TGFbetaR-II) by PCR and protein markers (Bcl2, cyclin D1, E-cadherin, hMLH1, ki67, MDM2, and P53) by immunohistochemistry. Using this method, we identified and abandoned potentially uninformative molecular markers in favour of more promising candidates. This approach conserves tissue resources, time, and money, and may be applicable to other studies.

Despite the belief that the etiology of and risk factors for rectal cancer might differ from those for colon cancer, relatively few studies have examined rectal cancer in relation to use of nonsteroidal antiinflammatory drugs (NSAIDs). The authors evaluated the association between NSAIDs and distal large bowel cancer in African Americans and whites, using data from a population-based case-control study of 1,057 incident cases of adenocarcinoma of the sigmoid colon, rectosigmoid junction, and rectum and 1,019 controls from North Carolina (2001–2006). NSAID use was inversely associated with distal large bowel cancer in whites (odds ratio (OR) = 0.60, 95% confidence interval (CI): 0.46, 0.79). The inverse association was evident for all types of NSAIDs but was slightly stronger with prescription NSAIDs, particularly selective cyclooxygenase 2 inhibitors (OR = 0.38, 95% CI: 0.25, 0.56). Compared with whites, a relatively weak inverse association was found in African Americans (OR = 0.87, 95% CI: 0.55, 1.40), although odds ratio heterogeneity by race could not be confirmed (P = 0.21). In addition, the strength of the association with NSAIDs varied by tumor location, suggesting more potent effects for rectal and rectosigmoid cancers than for sigmoid cancer. The chemopreventive potential of NSAIDs might differ by population and by tumor characteristics.

Glucuronidation by the UDP-glucuronosyltransferase enzymes (UGTs) is one of the primary detoxification pathways of dietary heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). In a population-based case-control study of 537 cases and 866 controls, we investigated whether colon cancer was associated with genetic variations in UGT1A1 and UGT1A9 genes and we determined if those variations modify the association between colon cancer and dietary HCA and PAH exposure. We measured functional UGT1A1 polymorphisms at positions −53 (*28; A(TA)6TAA to A(TA)7TAA), −3156 (G>A), −3279 (T>G) and the UGT1A9-275(T>A) polymorphism, and found no association with colon cancer overall. However, when stratified by race, the UGT1A1-3279 GG/TG intermediate/low activity genotypes were associated with an increased risk of colon cancer (odds ratio (OR) = 1.5, 95% confidence interval (CI)=1.1–2.0) in Caucasians. This finding is also supported by haplotype analyses where the UGT1A1-3279G-allele-bearing haplotype is overrepresented in case group. Overall, UGT1A1-53 and -3156 genotypes modified the association between dietary benzo(a)pyrene (BaP) and colon cancer (P for interaction=0.02 and 0.03, respectively). The strongest association was observed for those with

Background: Folate, other vitamin B cofactors, and genes involved in folate-mediated one-carbon metabolism all may play important roles in colorectal neoplasia. In this study, we examined the associations between dietary and circulating plasma levels of vitamins B2, B6, and B12 and risk colorectal adenomas.Methods: The Aspirin/Folate Polyp Prevention Study is a randomized clinical trial of folic acid supplementation and incidence of new colorectal adenomas in individuals with a history of adenomas (n = 1,084). Diet and supplement use were ascertained through a food frequency questionnaire administered at baseline. Blood collected at baseline was used to determine plasma B-vitamin levels. We used generalized linear regression to estimate risk ratios (RR) and 95% confidence intervals (95% CI) as measures of association.Results: We found a borderline significant inverse association with plasma B6 [pyridoxal 5′-phosphate (PLP)] and adenoma risk (adjusted RR Q4 versus Q1, 0.78; 95% CI, 0.61-1.00; Ptrend = 0.08). This association was not modified by folic acid supplementation or plasma folate. However, the protective association of PLP with adenoma risk was observed only among subjects who did not drink alcohol (Pinteraction = 0.03). Plasma B2 (riboflavin) was inversely associated with risk of advanced lesions (adjusted RR Q4 versus Q1, 0.51; 95% CI, 0.26-0.99; Ptrend = 0.12). No significant associations were observed between adenoma risk and plasma vitamin B12 or dietary intake of vitamin B2 and B6. When we examined specific gene-B-vitamin interactions, we observed a possible interaction between methylenetetrahydrofolate reductase -C677T and plasma B2 on risk of all adenomas.Conclusion: Our results suggest that high levels of PLP and B2 may protect against colorectal adenomas. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2136–45)

Objective Colorectal cancer incidence is greater among African Americans, compared to whites in the U.S., and may be due in part to differences in diet, genetic variation at metabolic loci, and/or the joint effect of diet and genetic susceptibility. We examined whether our previously reported associations between meat-derived heterocyclic amine (HCA) intake and colon cancer were modified by N -acetyltransferase 1 (NAT1) or 2 (NAT2) genotypes and whether there were differences by race. Methods In a population-based, case-control study of colon cancer, exposure to HCAs was assessed using a food-frequency questionnaire with a meat-cooking and doneness module, among African Americans (217 cases and 315 controls) and whites (290 cases and 534 controls). Results There was no association with NAT1*10 versus NAT1-non*10 genotypes for colon cancer. Among whites, there was a positive association for NAT2-“rapid/intermediate” genotype [odds ratio (OR) = 1.4; 95% confidence interval (CI) = 1.0, 1.8], compared to the NAT2-“slow” that was not observed among African Americans. Colon cancer associations with HCA intake were modified by NAT1, but not NAT2, regardless of race. However, the “at-risk” NAT1 genotype differed by race. For example, among African Americans, the positive association with 2-amino-1-methyl-6-phenyl-imidazo[4,5- b ]pyridine (PhIP) was confined to those with NAT1*10 genotype (OR = 1.8; 95% CI = 1.0, 3.3; P for interaction = 0.02, comparing highest to lowest intake), but among whites, an association with 2-amino-3,8-dimethylimidazo[4,5- f ]quinoxaline (MeIQx) was confined to those with NAT1-non*10 genotype (OR = 1.9; 95% CI = 1.1, 3.1; P for interaction = 0.03). Conclusions Our data indicate modification by NAT1 for HCA and colon cancer associations, regardless of race. Although the at-risk NAT1 genotype differs by race, the magnitude of the individual HCA-related associations in both race groups are similar. Therefore, our data do not support the hypothesis that NAT1 by HCA interactions contribute to differences in colorectal cancer incidence between African Americans and whites.

BACKGROUND: Persons with inflammatory bowel disease (IBD) have an increased risk of venous thromboembolism. We sought to examine whether the self-report of hormonal contraception (HC) as a proxy for exposure to estrogen-based contraception was less common for women with multiple risk factors for venous thromboembolism. METHODS: We examined the prevalence of personal use of hormonal birth control in a large internet-based cohort of patients with IBD. To determine whether HC was less common among patients with IBD with increased risk of thrombosis we estimated unadjusted and adjusted prevalence ratios (PRs) for the use of HC. RESULTS: Thousand four hundred ninety-nine female survey respondents answered optional fertility questions and were included in the analysis. The prevalence of HC was 33.7% (95% CI 30.6%-36.9%) among women with Crohns disease and was 32.6% (95% CI 28.6%-36.8%) for women with ulcerative colitis. Women with one risk factor for thrombosis were not significantly less likely to receive HC (PR = 0.91 95% CI: 0.76-1.08; adjusted PR = 0.94 95% CI: 0.80-1.11) compared with women without risk factors nor were women with 2 or more risk factors (PR = 1.10 95% CI 0.56-1.28; adjusted PR = 1.10 95% CI: 0.83-1.45). The use of an intrauterine device was also similar between women with and without risk factors for venous thromboembolism. CONCLUSIONS: The prevalence of HC use in women with multiple risk factors was similar to that in women without risk factors which represents an opportunity for prevention. Gastroenterologists should ask patients with IBD using HC about risk factors for thromboembolic disease to identify patients who may benefit from alternative contraception.

Background & Aims Regular screening with colonoscopy lowers colorectal cancer incidence and mortality. We aimed to determine patterns of repeat and surveillance colonoscopy and identify factors associated with overuse and underuse of colonoscopy. Methods We analyzed data from participants in a previous Veterans Health Administration (VHA) study who underwent outpatient colonoscopy at 25 VHA facilities between October 2007 and September 2008 (n = 1455). The proportion of patients who received a follow-up colonoscopy was calculated for 3 risk groups, which were defined on the basis of the index colonoscopy: no adenoma, low-risk adenoma, or high-risk adenoma. Results Colonoscopy was overused (used more frequently than intervals recommended by guidelines) by 16% of patients with no adenomas, 26% with low-risk adenomas, and 29% with high-risk adenomas. Most patients with high-risk adenomas (54%) underwent colonoscopy after the recommended interval or did not undergo colonoscopy. Patients who received a follow-up recommendation that was discordant with guidelines were more likely to undergo colonoscopy too early (no adenoma odds ratio [OR], 3.80; 95% confidence interval [CI], 2.31–6.25 and low-risk adenoma OR, 5.28; 95% CI, 1.88–14.83). Receipt of colonoscopy at nonacademic facilities was associated with overuse among patients without adenomas (OR, 5.26; 95% CI, 1.96–14.29) or with low-risk adenomas (OR, 3.45; 95% CI, 1.52–7.69). Performance of colonoscopies by general surgeons vs gastroenterologists (OR, 2.08; 95% CI, 1.02–4.23) and female sex of the patient (OR, 3.28; 95% CI, 1.06–10.16) were associated with overuse of colonoscopy for patients with low-risk adenomas. No factors examined were associated with underuse of colonoscopy among patients with high-risk adenomas. Conclusions In an analysis of patients in the VHA system, more than one fourth of patients with low-risk adenomas received follow-up colonoscopies too early, whereas more than one half of those with high-risk adenomas did not undergo surveillance colonoscopy as recommended. Our findings highlight the need for system-level improvements to facilitate the appropriate delivery of colonoscopy that is based on individual risk.

Background & Aims Colonic diverticula are the most common finding from colonoscopy examinations. Little is known about the distribution of colonic diverticula, which are responsible for symptomatic and costly diverticular disease. We aimed to assess the number, location, and characteristics of colonic diverticula in a large US screening population. Methods We analyzed data from a prospective study of 624 patients (mean age, 54 years) undergoing screening colonoscopy at the University of North Carolina Hospital from 2013 through 2015. The examination included a detailed assessment of colonic diverticula. To assess the association between participant characteristics and diverticula, we used logistic regression to estimate odds ratios and 95% confidence intervals. Results Of our population, 260 patients (42%) had 1 or more diverticula (mean number, 14; range, 1–158). Participants with diverticula were more likely to be older, male, and have a higher body mass index than those without diverticula. The distribution of diverticula differed significantly by race. Among white persons, 75% of diverticula were in the sigmoid colon, 11% in the descending splenic flexure, 6% in the transverse colon, and 8% were in the ascending colon or hepatic flexure. In black persons 64% of diverticula were in the sigmoid colon, 8% in the descending colon or splenic flexure, 7% in the transverse colon, and 20% in the ascending colon or hepatic flexure ( P = .0008). The proportion of patients with diverticula increased with age: 35% were 50 years or younger, 40% were 51–60 years, and 58% were older than 60 years. The proportion of patients with more than 10 diverticula increased with age: 8% were 50 years or younger, 15% were 51–60 years, and 30% were older than 60 years. Conclusions Older individuals not only have a higher prevalence of diverticula than younger individuals, but also a greater density, indicating that this is a progressive disease. Black persons have a greater percentage of their diverticula in the proximal colon and fewer in the distal colon compared with white persons. Understanding the distribution and determinants of diverticula is the first step in preventing diverticulosis and its complications.

Background Antibiotic treatment early in life is often not needed and has been associated with increased rates of subsequent diarrhoea. We estimated the impact of realistic interventions, which would prevent unnecessary antibiotic exposures before 6 months of age, on reducing childhood diarrhoeal rates. Methods In data from a prospective observational cohort study conducted in Vellore, India, we used the parametric g-formula to model diarrhoeal incidence rate differences contrasting the observed incidence of diarrhoea to the incidence expected under hypothetical interventions. The interventions prevented unnecessary antibiotic treatments for non-bloody diarrhoea, vomiting and upper respiratory infections before 6 months of age. We also modelled targeted interventions, in which unnecessary antibiotic use was prevented only among children who had already stopped exclusive breast feeding. Results More than half of all antibiotic exposures before 6 months (58.9%) were likely unnecessary. The incidence rate difference associated with removing unnecessary antibiotic use before 6 months of age was −0.28 (95% CI −0.46 to −0.08) episodes per 30 child-months. This implies that preventing unnecessary antibiotic exposures in just 4 children would reduce the incidence of diarrhoea by 1 from 6 months to 3 years of age. Conclusions Interventions to reduce unnecessary antibiotic use among young children could result in an important reduction in diarrhoeal rates. This work provides an example application of statistical methods which can further the aim of presenting epidemiological findings that are relevant to public health practice.

BACKGROUND & AIMS: Our aim was to establish the incidence of symptomatic upper gastrointestinal ulcers, ulcer perforation, ulcer obstruction, or bleeding episodes (PUBs) associated with the use of selective cyclooxygenase-2 inhibitors at standard clinical doses compared with placebo. We report here on the PUB outcomes associated with the use of rofecoxib 25 mg in a 3-year, multicenter, double-blind, placebo-controlled trial designed to determine the effect of rofecoxib on the risk of recurrent neoplastic polyps of the colon. METHODS: A total of 2587 patients with a history of colorectal adenomas underwent randomization to 25 mg/day of rofecoxib or to placebo. Investigator-reported PUBs were adjudicated by an external blinded committee. Kaplan-Meier and Cox proportional hazards techniques were used to estimate incidence and relative risks of PUBs in an intention-to-treat analysis. RESULTS: Patients assigned to rofecoxib had a higher incidence of confirmed PUBs than those randomized to placebo (.88 vs .18 events per 100 patient-years; relative risk, 4.9; 95% confidence interval, 1.98-14.54). The incidence of confirmed complicated PUBs (ulcer perforation, obstruction, or bleeds) was low, but was numerically higher in the rofecoxib than in the placebo group (.23 vs .06 events per 100 patient-years; relative risk, 3.8; 95% confidence interval, .72-37.46; P = .14). Rofecoxib increased the incidence of confirmed PUBs vs placebo in both low-dose aspirin users and nonusers. CONCLUSIONS: Among patients with a history of colorectal adenomas, the long-term use of 25 mg/day of rofecoxib was associated with an increased risk of clinically relevant upper gastrointestinal events when compared with placebo.

Background Calcium supplementation has been shown to decrease the risk of recurrence of colorectal adenomas in randomized trials. However, the duration of this protective effect after cessation of active supplementation is not known. Methods In the Calcium Polyp Prevention Study, 930 subjects with a previous colorectal adenoma were randomly assigned from November 1988 through April 1992 to receive placebo or 1200 mg of elemental calcium daily for 4 years. The Calcium Follow-up Study was an observational phase of the trial that tracked adenoma occurrence for an average of 7 years after the end of randomized treatment and gathered information regarding the use of medications, vitamins, and supplements during that time. We obtained follow-up information for 822 subjects, 597 of whom underwent at least one colonoscopy after the end of study treatment and are included in this analysis. Generalized linear models were used to compute relative risks (RRs) and 95% confidence intervals (CIs) for the effect of randomized calcium treatment on risk of adenoma recurrence during the first 5 years after study treatment ended and during the subsequent 5 years. Statistical tests were two-sided. Results During the first 5 years after randomized treatment ended, subjects in the calcium group still had a substantially and statistically significantly lower risk of any adenoma than those in the placebo group (31.5% versus 43.2%; adjusted RR = 0.63, 95% CI = 0.46 to 0.87, P = .005) and a smaller and not statistically significant reduction in risk of advanced adenomas (adjusted RR = 0.85, 95% CI = 0.43 to 1.69, P = .65). However, the randomized treatment was not associated with the risk of any type of polyp during the next 5 years. The findings were broadly similar when the analysis was restricted to subjects who did not report use of any calcium supplements after the treatment phase of the trial ended. Conclusion The protective effect of calcium supplementation on risk of colorectal adenoma recurrence extends up to 5 years after cessation of active treatment, even in the absence of continued supplementation.

Background and Aims The biological environment varies across the colorectum and may therefore affect neoplastic growth differently in the proximal and distal colon. The aim of the study was to evaluate the risk for recurrent adenomas and their anatomic location based on adenoma location at baseline colonoscopy. Methods Data were extracted from 3 adenoma prevention trials (n = 2430). Participants had at least 1 adenoma at baseline colonoscopy and underwent subsequent surveillance colonoscopy, at which time metachronous adenomas could be detected. We calculated the risk ratio (RR) and the 95% confidence interval (CI) for metachronous adenomas by location of the baseline lesion and considered the impact of advanced neoplasia and multiplicity. Results At baseline, 522 patients (21.5%) had adenomas only in the proximal colon, 1266 patients (52.1%) had adenomas only in the distal colorectum, and 642 (26.4%) had adenomas in both regions. Overall, 877 patients (36.5%) had metachronous adenomas during the follow-up period. Those with only proximal adenomas at baseline had a higher risk of metachronous adenomas compared with patients with only distal adenomas (RR, 1.17; 95% CI, 1.01–1.35). A greater proximal risk was found after restricting the analysis to patients with multiple proximal adenomas versus multiple distal adenomas (RR, 1.35; 95% CI, 1.10–1.67). The risk of recurrent adenomas on the same side was 48% higher for patients with only proximal adenomas at baseline compared with those with only distal adenomas at baseline (RR, 1.48; 95% CI, 1.22–1.80). Conclusions Patients with proximal adenomas only have a modestly greater risk of adenoma recurrence than patients with adenomas limited to the distal colon, and have a greater likelihood of adenoma recurrence on the same side compared with patients with distal adenomas. This observation suggests that biological factors may differentially affect neoplasia growth across the colon.

BACKGROUND Substantial racial disparities exist in colorectal cancer (CRC) survival. OBJECTIVE This was an exploratory study to assess the racial differences in dietary changes in relation to quality of life (QoL), recurrence, and survival after a CRC diagnosis. DESIGN Four hundred fifty-three stage II CRC patients were enrolled in the cohort study through the North Carolina Central Cancer Registry. Self-reported diet, physical activity, treatment, comorbidities, demographic characteristics, and QoL were collected at diagnosis and 12 and 24 mo after diagnosis. QoL was assessed with the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) and the Medical Outcomes 12-Item Short Form Health Survey (SF-12) inventories. An overall dietary index score was calculated. Generalized estimating equations and logistic regression models were used to explore potential associations. Statistical power for this study was ∼50%. RESULTS African Americans (n = 81) were more likely to increase intakes of reduced-fat milk, vegetables, and fruit and decrease intakes of regular cheese, red meat, fried food, fast food, and fat (P < 0.05) than were Caucasians (n = 184) 24 mo after diagnosis. The least-squares means ± SEs for changes in dietary index were 6.05 ± 0.40 and 4.07 ± 0.27 for African Americans and Caucasians, respectively (P < 0.001). African Americans exhibited higher scores on portions of the FACT-C (colorectal cancer subscale: β = 1.04; 95% CI: 0.26, 1.82) and the SF-12 (Physical Component Summary: β = 2.49; 95% CI: 0.51, 4.48). Those who improved their dietary quality over 24 mo had lower risk of recurrence and mortality combined (OR: 0.42; 95% CI: 0.25, 0.72). CONCLUSIONS African Americans made more healthful changes in diet and had a higher QoL than did Caucasians in this underpowered study that used self-reported dietary data. No racial differences in recurrence or survival were evident, although improvements in dietary quality did reveal survival benefits overall. More prospective research on racial disparities in health behavior changes after diagnosis is desperately needed.

Most cancer deaths are due to metastases. Markers of epithelial-mesenchymal transition (EMT) measured in primary tumor cancer cells could be helpful to assess patient risk of metastatic disease, even among those otherwise diagnosed with local disease. Previous studies of EMT markers and patient outcomes used inconsistent methods and did not compare the clinical impact of different expression cut points for the same marker. Using digital image analysis, we measured the EMT markers Snail and E-cadherin in primary tumor specimens from 190 subjects in tissue microarrays from a population-based prospective cohort of colorectal cancer patients and estimated their associations with time-to-death. After measuring continuous marker expression data, we performed a systematic search for the cut point for each marker with the best model fit between dichotomous marker expression and time-to-death. We also assessed the potential clinical impact of different cut points for the same marker. After dichotomizing expression status at the statistically-optimal cut point, we found that Snail expression was not associated with time-to-death. When measured as a weighted average of tumor cores, low E-cadherin expression was associated with a greater risk of dying within 5 years of surgery than high expression (risk difference = 33 %, 95 % confidence interval 3–62 %). Identifying a clinically-optimal cut point for an EMT marker requires trade-offs between strength and precision of the association with patient outcomes, as well as consideration of the number of patients whose treatments might change based on using the marker at a given cut point.

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.

Antibiotics are frequently used to treat childhood illnesses, especially respiratory tract infections, otitis media and diarrhea. However, many of these infections are viral and/or self-limiting, such that antibiotics are not necessary.1–3 The overuse of antibiotics among children has been reported around the world,1,4,5 and antibiotic over-prescribing by primary care physicians6,7 in India is further compounded by the ability to purchase antibiotics over the counter without a prescription8 in spite of government regulations.9 Often, the primary rationale given for restricting antibiotic use is to slow the development of antimicrobial resistance.10,11 However, recent evidence has suggested antibiotics may also have a direct negative impact on the patients prescribed the drugs, primarily through interactions with the gastrointestinal (GI) microbiota.11 The development of the GI microbiota in the first few months of life coincides with a critical period of intestinal structure and immune system maturation.12–14 A healthy microbiota is important in the early life defense against GI infections by providing a barrier effect that inhibits the attachment and growth of pathogens.15,16 Antibiotics impact the diversity and composition of the GI microbiota, and some of these effects can persist long after treatment is completed,17,18 especially among infants.19–23 These exposures have been further associated with impaired GI functioning, intestinal inflammation, and increased intestinal permeability and risk of systemic infections.21,24,25 Given the potential negative impact of antibiotics on the developing microbiota, we assessed whether antibiotic exposure in the first 6 months of life affected subsequent rates of all-cause diarrhea from 6 months to 3 years of age in a birth cohort from Vellore, India. We also explored the impact of exclusive breastfeeding, which may modify this effect given the beneficial role of breast milk on the microbiota.26–28

OBJECTIVE To examine health behaviors (fruit/vegetable intake and physical activity) and their association with social cognitive theory (SCT) constructs among colorectal cancer (CRC) survivors (n=304) and comparable non-CRC-affected participants (n = 521). METHODS Baseline data were analyzed bivariately and modeled with linear regression. Participants were 48% female, 36% African American (mean age = 67). RESULTS Behaviors were comparable between groups, but survivors perceived more social support for behaviors (P

Context: Geographic and racial variations in cancer incidence have been observed. Studies of colorectal carcinoma indicate a higher incidence and mortality rate for blacks than for whites in the United States. Purpose: We evaluated the effect of rural versus urban residence on colon cancer risk and stage of disease at diagnosis in blacks and whites. Methods: Interviews were conducted with 558 colon cancer cases and 952 controls enrolled in the North Carolina Colon Cancer Study, a population-based case-control study of blacks and whites residing in 33 contiguous counties. Findings: Residence in a rural area was associated with increased colon cancer risk (odds ratio, 1.4; 95% confidence interval, 1.1-1.8). This association was no longer significant after controlling for recent use of colorectal cancer screening tests (odds ratio, 1.2; 95% confidence interval, 0.9-1.6). Risk estimates were not modified by race nor were they markedly different for extent of disease at diagnosis. However, colorectal cancer screening rates were lower for blacks than for whites. Conclusion: Our findings suggest that rural blacks and whites are at increased risk of colon cancer regardless of stage of disease at diagnosis than their urban counterparts; this relationship may be mediated by screening behavior.

Positive and Negative Predictive Values: Use of Inflammatory Bowel Disease Serologic Markers

We evaluated associations between the availability and adequacy of emotional support and health–related quality of life (QOL) among Blacks and Whites, and individuals varying in socioeconomic status. While both aspects of emotional support were associated directly with enhanced quality of life, important interaction effects were observed. First, adequacy of emotional support had a beneficial effect for Blacks and Whites of higher education; however, it was associated with better physical health–related QOL for Whites but not Blacks of lower education (b = 2.59, t(1, 845) = 2.82, p = .005). Furthermore, having greater available emotional support was associated with poorer quality of life for Blacks but not Whites (b = −3.99, t(1, 842) = −2.56, p =.01) and for Blacks of lower education compared to Whites of similar status (b = 2.21, t(1, 842) = 2.19, p = .03). Our findings suggest that emotional support may not be as beneficial among Blacks compared to Whites, and particularly among Blacks with les...

OBJECTIVE: The aim of this study was to determine the relationship between fat, fiber, and meat intake, and risk of colorectal adenoma recurrence. METHODS: We determined adenoma recurrence and dietary intake for 1,520 participants in two randomized trials: The Antioxidant Polyp Prevention Study and Calcium Polyp Prevention Study. Subjects underwent baseline colonoscopy with removal of all adenomas, and dietary intake was estimated with a validated semiquantitative food frequency questionnaire. Follow-up colonoscopy was performed 1 and 4 yr later. Pooled risk ratios for adenoma recurrence were obtained by generalized linear regression, with adjustment for age, sex, clinical center, treatment category, study, and duration of observation. RESULTS: In the total colorectum, fiber intake was weakly and nonsignificantly associated with a risk for all adenomas (RR quartile 4 vs quartile 1 = 0.85, 95% CI 0.69‐1.05) and advanced adenomas (RR = 0.88, 95% CI 0.54‐1.44). Associations were stronger for adenomas in the proximal colon (RR = 0.73, 95% CI 0.56‐0.97) and some fiber subtypes (fruit and vegetable, grain). There was no association between fat or total red meat intake and risk of adenoma or advanced adenoma recurrence. However, when considering other meats, risk (quartile 4 vs quartile 1) for advanced adenoma was increased for processed meat (RR = 1.75, 95% CI 1.02‐2.99) and decreased for chicken (RR = 0.61, 95% CI 0.38‐0.98). CONCLUSION: The inverse associations between fiber intake and risk of adenoma recurrence we observed are weak, and not statistically significant. Our data indicate that intake of specific meats may have different effects on risk. (Am J Gastroenterol 2005;100:2789‐2795)

Medical research funding in the United States has 4 predominant sources: the federal government; the pharmaceutical industry; institutions; and private foundations. In each case, the grant application process is the first step in obtaining funding. Successful grant applications are logical, organized, and easy to read. The research question should be both specific and significant. Comprehensive and detailed study methods addressing the study population, timeline, and data collection and management increase the likelihood of obtaining funding. Funding for inflammatory bowel disease preclinical and clinical research is available from the National Institutes of Health and Crohn's & Colitis Foundation of America.

African Americans have the highest colon cancer incidence and mortality rates among all US ethnic groups. Epidemiologic studies suggest that use of nonsteroidal antiinflammatory drugs (NSAIDs) is associated with a reduced risk of colon cancer, but no study to date with adequate sample size has reported on the association among African Americans. The authors examined the association between NSAID use and risk of colon cancer in a population-based, case-control study in North Carolina that enrolled 731 African-American (294 cases, 437 controls) and 960 White (349 cases, 611 controls) participants between 1996 and 2000. Odds ratios were calculated using unconditional logistic regression for categories of NSAIDs and colon cancer risk. Inverse associations between regular NSAID use and colon cancer were similar for African Americans (odds ratio = 0.41, 95% confidence interval: 0.22, 0.77) and Whites (odds ratio = 0.48, 95% confidence interval: 0.28, 0.83) but stronger for women than men. Inverse associations were slightly weaker for occasional versus regular NSAID use, but they were similar for aspirin and nonaspirin NSAID use. These results add new knowledge suggesting that the protective effect of NSAIDs against colon cancer is similar among African Americans and Whites.

The UDP-glucuronosyltransferase 1A7 (UGT1A7) gene is polymorphic and encodes an enzyme involved in the detoxification of heterocyclic amines (HCA) and polycyclic aromatic hydrocarbons (PAH). Consumption of pan-fried and well-done meat are surrogates for HCA and PAH exposure and are possibly associated with colon cancer. We have evaluated whether UGT1A7 allelic variations are associated with colon cancer and whether UGT1A7 genotype modified associations among meat intake, exposure to HCAs and PAHs, and colon cancer in a population-based case-control study of African Americans (197 cases and 202 controls) and whites (203 cases and 210 controls). As part of a 150-item food frequency questionnaire, meat intake was assessed by cooking method and doneness and used to estimate individual HCA and PAH exposure. UGT1A7 alleles (UGT1A7*1, UGT1A7*2, UGT1A7*3, and UGT1A7*4) were measured and genotypes were categorized into predicted activity groups (high: *1/*1, *1/*2, *2/*2; intermediate: *1/*3, *1/*4, *2/*3; low: *3/*3, *3/*4, *4/*4). There was no association with UGT1A7 low versus high/intermediate genotype [odds ratio (OR), 1.1; 95% confidence interval (95% CI), 0.7-1.8], regardless of race. Greater than additive joint effects were observed for UGT1A7 low genotype and HCA-related factors. For example, equal to or greater than the median daily intake of the HCA, 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and having UGT1A7 low genotype was positively associated with colon cancer (OR, 2.4; 95% CI, 1.2-4.8), compared with less than the median daily intake and UGT1A7 high/intermediate genotypes. These data suggest that the associations among cooked meat–derived compound exposure, and colon cancer are modified by the UGT1A7 genotype.