Proton pump inhibitors and the risk of colorectal cancer

INTRODUCTION: Proton pump inhibitor (PPI) use is associated with increased serum gastrin levels and bacterial overgrowth, resulting in more toxic bile salt formation. Concern has risen that these factors may increase the risk of developing colorectal neoplasia.
AIM: To investigate the association between the use of PPIs and the risk of colorectal cancer.
METHODS: A population-based case-control study was conducted within the Dutch Primary Care Information (IPCI) database over the period 1996–2005. Cases with colorectal cancer were matched with up to 20 controls on age, gender, calendar time, and duration of follow-up prior to diagnosis. Cumulative exposure to PPIs was assessed in the 5 yr prior to diagnosis with a 1-yr lag time analysis. We calculated adjusted odds ratios (OR) with 95% confidence intervals (95% CI) using multivariate, conditional logistic regression analysis.
RESULTS: Within the source population of 457,024 persons, we identified 595 colorectal cancer cases. The odds of colorectal cancer were not increased among patients ever using PPIs compared with patients who never used PPIs (OR 0.85, 95% CI 0.63–1.16). Also, the use of PPIs for >365 days was not associated with a greater risk of colorectal cancer (OR 0.79, 95% CI 0.44–1.41) compared with nonusers. The odds of colorectal cancer in neither the right nor the left hemicolon were significantly increased in patients using PPIs.
CONCLUSION: The present study indicates no association between PPI use and the risk of colorectal cancer. Larger numbers of long-term PPI users are needed to confirm the absence of a risk-increasing effect of long-term PPI exposure.     

Discontinuation of nonsteroidal anti-inflammatory drug therapy and risk of acute myocardial infarction

BACKGROUND: Systemic inflammation has been shown to be associated with an increased risk of acute myocardial infarction (AMI). However, the effect of the use of nonsteroidal anti-inflammatory drugs (NSAIDs) on the risk of AMI has not yet been well defined. We therefore studied the risk of AMI during NSAID exposure and after the cessation of NSAID therapy. METHODS: We conducted a large case-control analysis on the British General Practice Research Database. The study included 8688 cases with a first-time AMI between 1995 and 2001 and 33 923 controls, matched to cases on age, sex, calendar time, and general practice attended. RESULTS: After adjusting for hypertension, hyperlipidemia, diabetes mellitus, ischemic heart disease, rheumatoid arthritis, systemic lupus erythematosus, acute chest infection, body mass index, smoking, and aspirin use, the risk of AMI was 1.52 (95% confidence interval [CI], 1.33-1.74) for subjects who stopped taking NSAIDs 1 to 29 days prior to the index date, compared with nonusers. The risk was highest in subjects with rheumatoid arthritis or systemic lupus erythematosus (adjusted OR, 3.68 [95% CI, 2.36-5.74]) and for subjects who discontinued therapy with NSAIDs after previous long-term use (adjusted OR, 2.60 [95% CI, 1.84-3.68]). Current and past NSAID use (discontinued therapy >/=60 days prior to the index date) were not associated with an increased risk of AMI (adjusted OR, 1.07 [95% CI, 0.96-1.19] and 1.05 [95% CI, 0.99-1.12], respectively). CONCLUSION: Our findings suggest that the risk of AMI is increased during several weeks after the cessation of NSAID therapy.     

Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis: a meta-analysis

BACKGROUND: Published data on the risk of colorectal neoplasia in patients with ulcerative colitis with and without primary sclerosing cholangitis are conflicting. A meta-analysis was performed to synthesize available publications and to compare the risk of colorectal neoplasia in patients with ulcerative colitis with and without primary sclerosing cholangitis. METHODS: By using MEDLINE and manual search methods, studies were identified that compared the risk of colorectal neoplasia (dysplasia and carcinoma) in patients with ulcerative colitis with and without primary sclerosing cholangitis. In addition, citations were reviewed in relevant articles and proceedings from gastroenterology meetings, and investigators were contacted when data were incomplete. The summary odds ratio (OR) was then calculated for the risk for patients with ulcerative colitis and primary sclerosing cholangitis of having colorectal neoplasia develop compared with that of patients with ulcerative colitis without primary sclerosing cholangitis. RESULTS: Eleven studies met all eligibility criteria for the meta-analysis. Patients with ulcerative colitis and primary sclerosing cholangitis are at increased risk of colorectal dysplasia and carcinoma compared with patients with ulcerative colitis alone; OR 4.79: 95% CI [3.58, 6.41] with the Mantel-Haenszel method, and OR 5.11: 95% CI [3.15, 8.29] with the Der Simonian and Laird method. This increased risk is present even when the risk of colorectal carcinoma alone is considered; OR 4.09: 95% CI [2.89, 5.76] and OR 4.26: 95% CI [2.80, 6.48] by using, respectively, the Mantel-Haenszel and the Der Simonian and Laird methods. CONCLUSIONS: Patients with ulcerative colitis and primary sclerosing cholangitis have a significantly higher risk for the development of colorectal neoplasia than patients with ulcerative colitis but not primary sclerosing cholangitis. More intensive colonoscopic surveillance should be considered for patients with ulcerative colitis and primary sclerosing cholangitis.     

Predictors of proximal neoplasia in patients without distal adenomatous pathology

BACKGROUND: Previous colorectal cancer screening studies have observed that some patients may have advanced proximal neoplasia without distal findings. Since these studies have included only gender, age, and family history as risk factors, they are limited in their ability to identify predictors of isolated proximal neoplasia. METHODS: Data were collected from the charts of 1,988 patients who presented for colonoscopy. Information gathered included endoscopic findings, histology, known risk factors for colorectal neoplasia, and smoking pattern. Our main outcome was the presence of proximal adenomatous neoplasia in patients who had no distal adenomas. We defined significant neoplasia as adenocarcinoma, high-grade dysplasia, villous polyps, adenomas 1 cm or greater or more than two adenomas of any size. RESULTS: Fifty-five patients had isolated significant proximal neoplasia that would have been missed on a flexible sigmoidoscopy. While patients older than 60 yr had a greater risk for this neoplasia (odds ratio = 3.01: 95% CI = 1.66-4.23; p < 0.001), those who took a daily aspirin had a reduced risk (OR = 0.60; 95% CI = 0.30-0.88; p < 0.05). A family history of colorectal cancer increased the patient's risk of having any adenomas (OR = 2.01; 95% CI = 1.33-3.40; p < 0.01) or villous tissue (OR = 2.03; 95% CI = 1.27-3.51; p < 0.05) in the proximal colon without distal findings. Smoking was associated with an increased risk of large (> 1 cm) isolated proximal tubular polyps (OR = 2.71; 95% CI = 1.64-4.46; p < 0.01) as well as isolated significant proximal neoplasia (OR = 2.30; 95% CI = 1.59-3.31; p < 0.01). CONCLUSIONS: Age greater than 60 yr, a history of at least 10 pack-years of smoking, and a family history of colorectal cancer increased the risk of finding significant proximal polyps in patients without distal pathology.     

Effect of antisecretory drugs and nitrates on the risk of ulcer bleeding associated with nonsteroidal anti-inflammatory drugs, antiplatelet agents, and anticoagulants

OBJECTIVES: After the withdrawal of some cyclooxygenase-2 (COX-2) selective inhibitors, traditional nonsteroidal anti-inflammatory drug (NSAID) use has increased, but without additional prevention strategies against upper gastrointestinal (GI) complications in many cases. Here, we report the effect of antisecretory drugs and nitrates on the risk of upper GI peptic ulcer bleeding (UGIB) associated with nonselective NSAIDs, aspirin, antiplatelet agents, and anticoagulants. METHODS: This case-control study matched 2,777 consecutive patients with UGIB (confirmed by endoscopy) with 5,532 controls (2:1). Adjusted relative risks (RR) of UGIB are reported. RESULTS: Proton pump inhibitors (PPIs) (RR 0.33, 95% confidence interval [CI] 0.27-0.39), H2-receptor antagonists (H2-RAs) (RR 0.65, 95% CI 0.50-0.85), and nitrates (RR 0.52, 95% CI 0.38-0.70) reduced UGIB risk. PPI use was associated with greater reductions among both traditional NSAID (RR 0.13, 95% CI 0.09-0.19 vs RR 0.30, 95% CI 0.17-0.53 with H2-RAs; RR 0.48, 95% CI 0.19-1.24 with nitrates) and low-dose aspirin users (RR 0.32, 95% CI 0.22-0.51 vs RR 0.40, 95% CI 0.19-0.73 with H2-RA; RR 0.69, 95% CI 0.36-1.04 with nitrates), and among patients taking clopidogrel (RR 0.19, 95% CI 0.07-0.49). For patients taking anticoagulants, use of nitrates, H2-RA, or PPIs was not associated with a significant effect on UGIB risk. CONCLUSION: Antisecretory agent or nitrate treatment is associated with reduced UGIB RR in patients taking NSAID or aspirin. Only PPI therapy was associated with a marked, consistent risk reduction among patients receiving all types of agents (including nonaspirin antiplatelet agents). Protection was not apparent in patients taking anticoagulants.     

Health-related quality of life predicts future health care utilization and mortality in veterans with self-reported physician-diagnosed arthritis: the veterans arthritis quality of life study

OBJECTIVE: To investigate whether health-related quality of life (HRQOL) measures predict health care utilization and mortality in a cohort of veterans with self-reported physician-diagnosed arthritis. METHODS: A cohort of veterans from the Upper Midwest Veterans Integrated Service Network (VISN) was mailed a self-administered questionnaire that was composed of the SF-36V (modified from SF-36 for use in veterans) and questions regarding demographics, current smoking status, limitation of activities of daily living (ADLs), and preexisting physician-diagnosed medical conditions, including arthritis. Within subjects reporting physician-diagnosed arthritis, we analyzed the associations between the SF-36V component summary scales (physical and mental component summary, PCS and MCS, respectively) and the occurrence of any hospitalization, number of hospitalizations, number of outpatient visits, and mortality, for the year after survey administration, using multivariable regression analyses. RESULTS: Of 34,440 survey responders who answered a question regarding arthritis, 18,464 (58%) subjects reported physician-diagnosed arthritis. Arthritic patients in the lowest tertile of PCS scores had significantly higher odds of any hospitalization (Odds ratio (OR) 1.49, 95% confidence interval (CI) [1.25-1.76]) and mortality (OR 1.69, 95% CI [1.18-2.42]), and a significantly higher number of hospitalizations/year (Rate ratio (RR) 1.09, 95% CI [1.05-1.13]) and outpatient visits/year (RR 1.07, 95% CI [1.03-1.11]). Arthritic patients in the lowest tertile of MCS scores had significantly higher odds of any hospitalization (OR 1.20, 95% CI [1.02-1.41]), mortality (OR 2.14, 95% CI [1.56-2.94]), and a significantly higher number of hospitalizations/year (RR 1.05, 95% CI [1.02-1.09]) and outpatient visits/year (RR 1.07, 95% CI [1.03-1.11]). CONCLUSIONS: HRQOL, as assessed by the SF-36V, predicts future inpatient and outpatient health care utilization and mortality in veterans with self-report of physician-diagnosed arthritis.     

Risk factors for colorectal neoplasia in inflammatory bowel disease: a nested case-control study from Copenhagen county, Denmark and Olmsted county, Minnesota

OBJECTIVES: Population-based data on risk factors and protective factors for colorectal dysplasia and cancer in patients with inflammatory bowel disease (IBD) are sparse. We conducted a nested case-control study of such factors in two well-described IBD cohorts from Copenhagen County, Denmark and Olmsted County, Minnesota. METHODS: Forty-three neoplasia cases were matched on six criteria to 1-3 controls (N = 102). Medical records were scrutinized for demographic and clinical data. For each variable, the odds of neoplasia were estimated using conditional logistic regression. RESULTS: Primary sclerosing cholangitis (PSC) (odds ratio [OR] 6.9, 95% confidence interval [CI] 1.2-40), percentage of disease course with clinically active disease (OR [per 5% increase] 1.2, 95% CI 0.996-1.4), and >or=1 yr of continuous symptoms (OR 3.2, 95% CI 1.2-8.6) were associated with neoplasia, whereas a borderline association with median number of small-bowel x-rays (OR 1.3, 95% CI 0.96-1.6) was observed. We did not observe a protective effect of frequency of physician visits (OR 1.4, 95% CI 0.96-2.0), number of colonoscopies (OR 1.4, 95% CI 1.0-2.1), cumulative dose of sulfasalazine (OR [per 1,000 g] 1.1, 95% CI 1.0-1.3) and mesalamine (OR [per 1,000 g] 1.3, 95% CI 0.9-1.9), or partial intestinal resections (OR 1.5, 95% CI 0.3-7.1). CONCLUSIONS: Subgroups of IBD patients-those with PSC, severe long-standing disease, and exposure to x-ray-were at greater risk of colorectal neoplasia. The protective effect of close follow-up, colonoscopy, and treatment with 5-aminosalicylates was questionable.     

Evaluation of a risk score based on dietary and lifestyle factors to target a population at risk in colorectal cancer screening

BackgroundThe aim of our study was to assess three risk scores to predict lesions, advanced neoplasia (high-risk adenomas and colorectal cancer (CRC)) and CRC in individuals who participate to colorectal cancer screening.MethodsThe data of dietary and lifestyle risk factors were carried out during 2 mass screening campaigns in France (2013–2016) and the FOBT result was collected until December 2018. The colonoscopy result in positive FOBT was recovered. Three risk scores (Betés score, Kaminski score and adapted-HLI) were calculated to detect individuals at risk of lesions.ResultsThe Betés score had an AUROC of 0.63 (95% CI, [0.61–0.66]) for lesions, 0.65 (95% CI, [0.61–0.68]) for advanced neoplasia and 0.65 (95% CI, [0.58–0.72]) for predicting screen-detected CRC.The adapted HLI score had an AUROC of 0.61 (95% CI, [0.58–0.65]) for lesions, 0.61 (95% CI, [0.56–0.65]) for advanced neoplasia and 0.55 (95% CI, [0.45–0.65]) for predicting screen-detected CRC.The Kaminski score had an AUROC of 0.65 (95% CI, [0.63–0.68]) for lesions, 0.65 (95% CI, [0.61–0.68]) for advanced neoplasia and 0.69 (95% CI, [0.62–0.76]) for predicting screen-detected CRC.ConclusionA simple questionnaire based on CRC risk factors could help general practitioners to identify participants with higher risk of significant colorectal lesions and incite them to perform the fecal occult blood test.     

Effect of risk factors on complicated and uncomplicated ulcers in the TARGET lumiracoxib outcomes study

BACKGROUND & AIMS: Selective cyclooxygenase-2 inhibitors were developed to reduce the gastrointestinal risk associated with nonsteroidal anti-inflammatory drugs (NSAIDs). The Therapeutic Arthritis Research and Gastrointestinal Event Trial was the largest study to evaluate primarily the gastrointestinal safety outcomes of selective cyclooxygenase-2 inhibitors. Data from the Therapeutic Arthritis Research and Gastrointestinal Event Trial were used to identify risk factors and investigate the safety of lumiracoxib in subgroups. METHODS: Patients with osteoarthritis (age, >or=50 y) were randomized to receive lumiracoxib 400 mg once daily, naproxen 500 mg twice daily, or ibuprofen 800 mg 3 times daily for 12 months. Events were categorized by a blinded adjudication committee. The primary end point was all definite or probable ulcer complications. RESULTS: For patients taking NSAIDs, factors associated with an increased risk of ulcer complications were age 65 years or older (hazard ratio [HR], 2.30; 95% confidence interval [CI], 1.48-3.59), previous history of gastrointestinal bleed or ulcer (HR, 3.61; 95% CI, 1.86-7.00), non-Caucasian racial origin (HR, 2.10; 95% CI, 1.35-3.27), and male sex (HR, 1.70; 95% CI, 1.08-2.68). With lumiracoxib, significant risk factors were age 65 years or older (HR, 3.18; 95% CI, 1.40-7.20), male sex (HR, 2.60; 95% CI, 1.25-5.40), non-Caucasian racial origin (HR, 2.16; 95% CI, 1.02-4.59), and concomitant aspirin use (HR, 2.89; 95% CI, 1.40-5.97). Increased risks in patients age 65 years and older were increased further if other risk factors were present. Lumiracoxib maintained an advantage over NSAIDs across all subgroups except aspirin use. CONCLUSIONS: Lumiracoxib was associated with a reduced risk of ulcer complications compared with NSAIDs in all significant subgroups except aspirin users.     

Colonoscopic screening of first-degree relatives of patients with large adenomas: increased risk of colorectal tumors

BACKGROUND & AIMS: The risk of developing colorectal neoplasia is not well established among family members of individuals with large adenomas, and screening strategies remain under debate in this population. This study aimed at quantifying the risk of colorectal adenomas and cancers using colonoscopic screening in first-degree relatives of patients with large adenomas. METHODS: This case-control study was performed in 18 endoscopic units of French nonuniversity hospitals. A colonoscopy was offered to first-degree relatives of 306 index cases with adenomas > or =10 mm if they were alive, aged 40-75 years, and could be contacted by the index case. Among them, 168 were examined and matched for age, sex, and geographical area with 2 controls (n = 307). Controls were randomly selected from 1362 consecutive patients aged 40-75 years having undergone a colonoscopy for minor symptoms. RESULTS: The prevalence of large adenomas and cancers was 8.4% and 4.2%, in relatives and controls, respectively. Odds ratios (ORs) associated with a history of large adenomas in relatives were 2.27 (95% confidence interval [CI], 1.01-5.09) for cancers or large adenomas, 1.21 (95% CI, 0.68-2.15) for small adenomas, and 1.56 (95% CI, 0.96-2.53) for all colorectal neoplasia. The risk of large adenomas and cancers was higher in relatives of index cases younger than 60 years (OR, 3.82; 95% CI, 0.92-15.87) and when the index case had large distal adenomas (OR, 3.14; 95% CI, 1.27-7.73). CONCLUSIONS: First-degree relatives of patients with large adenomas are at increased risk of developing colorectal cancers or large adenomas. This result has implications for screening in this high-risk population.     

Risk of upper gastrointestinal ulcer bleeding associated with selective cyclo-oxygenase-2 inhibitors, traditional non-aspirin non-steroidal anti-inflammatory drugs, aspirin and combinations

BACKGROUND: The risks and benefits of coxibs, non-steroidal anti-inflammatory drugs (NSAIDs), and aspirin treatment are under intense debate. OBJECTIVE: To determine the risk of peptic ulcer upper gastrointestinal bleeding (UGIB) associated with the use of coxibs, traditional NSAIDs, aspirin or combinations of these drugs in clinical practice. METHODS: A hospital-based, case-control study in the general community of patients from the National Health System in Spain. The study included 2777 consecutive patients with endoscopy-proved major UGIB because of the peptic lesions and 5532 controls matched by age, hospital and month of admission. Adjusted relative risk (adj RR) of UGIB determined by conditional logistic regression analysis is provided. RESULTS: Use of non-aspirin-NSAIDs increased the risk of UGIB (adj RR 5.3; 95% confidence interval (CI) 4.5 to 6.2). Among non-aspirin-NSAIDs, aceclofenac (adj RR 3.1; 95% CI 2.3 to 4.2) had the lowest RR, whereas ketorolac (adj RR 14.4; 95% CI 5.2 to 39.9) had the highest. Rofecoxib treatment increased the risk of UGIB (adj RR 2.1; 95% CI 1.1 to 4.0), whereas celecoxib, paracetamol or concomitant use of a proton pump inhibitor with an NSAID presented no increased risk. Non-aspirin antiplatelet treatment (clopidogrel/ticlopidine) had a similar risk of UGIB (adj RR 2.8; 95% CI 1.9 to 4.2) to cardioprotective aspirin at a dose of 100 mg/day (adj RR 2.7; 95% CI 2.0 to 3.6) or anticoagulants (adj RR 2.8; 95% CI 2.1 to 3.7). An apparent interaction was found between low-dose aspirin and use of non-aspirin-NSAIDs, coxibs or thienopyridines, which increased further the risk of UGIB in a similar way. CONCLUSIONS: Coxib use presents a lower RR of UGIB than non-selective NSAIDs. However, when combined with low-dose aspirin, the differences between non-selective NSAIDs and coxibs tend to disappear. Treatment with either non-aspirin antiplatelet or cardioprotective aspirin has a similar risk of UGIB.     

Risk factors for gastrointestinal bleeding: a hospital-based case-control study

QUESTIONS UNDER STUDY/PRINCIPLES: Gastrointestinal (GI) bleeding is a frequent serious adverse drug reaction, potentially causing hospital admission and death. We investigated risk factors for a first-time GI bleeding leading to hospital admission with a focus on drugs and drug-drug interactions (DDIs). METHODS: We conducted a hospital-based case-control study at the Kantonsspital Winterthur, encompassing 74 patients with a first-time GI bleeding in the year 2005 and 148 controls, matched to cases on age, sex and calendar time. RESULTS: Multivariate models including various drugs and comorbidities revealed a significant risk for GI bleeding for treatment with nonsteroidal antiinflammatory drugs (NSAIDs) (odds ratio [OR] 8.6, 95% confidence interval [CI] 3.1-23) and thrombocyte aggregation inhibitors (OR 2.2, 95% CI 1.1-4.6). Anticoagulation alone in the therapeutic international normal ratio (INR) range was not associated with bleedings (OR 0.9, 95% CI 0.4-2.3), but INR values > or = 4 were associated with an increased bleeding risk (OR 13, 95% CI 1.2-150). DDI models yielded increased risk estimates for combined use of NSAID and glucocorticoids (OR 20, 95% CI 1.6-257), and for combined use of oral anticoagulants and NSAIDs (8 cases, 0 controls, crude OR approx. 20). CONCLUSION: The findings of this small hospital-based case-control analysis suggest that a first-time GI bleeding is associated with INR values above the therapeutic range, but not with well-controlled oral anticoagulation in the absence of other risk factors such as DDIs. The combinations of glucocorticoids or oral anticoagulants with NSAIDs carry a high risk for GI bleeding.     

A prospective study of genetic polymorphisms in the cytochrome P-450 2C9 enzyme and the risk for distal colorectal adenoma.

BACKGROUND & AIMS: Regular aspirin use is associated with a reduced risk for colorectal adenoma, whereas smoking increases risk. The cytochrome P-450 (CYP) 2C9 (CYP2C9) enzyme is involved in the metabolism of several drugs, including possibly aspirin, and such carcinogens as smoking-related polycyclic aromatic hydrocarbons. Genetic variation in this enzyme may modulate the influence of aspirin and smoking on adenoma risk. METHODS: We examined the risk for incident distal colorectal adenoma according to CYP2C9 genotype, aspirin use, and smoking in a prospective nested case-control study of women. RESULTS: Among 394 cases and 396 controls, women with at least 1 variant CYP2C9 allele had a significantly greater risk for adenoma (multivariate odds ratio [OR], 1.56; 95% confidence interval [CI], 1.13-2.15; P = 0.007). Although women who used aspirin regularly (>/=2 standard tablets/wk) experienced a lower risk for adenoma compared with non-regular users, the effect was similar irrespective of genotype. Women who smoked >20 pack-years had an OR of adenoma of 1.50 (95% CI, 1.07-2.12; P = 0.02) compared with those who smoked 20 pack-years, the OR of adenoma was 2.50 (95% CI, 1.44-4.38; P = 0.001) compared with women with no variant alleles who smoked 相似文献   

First-degree relatives of patients with advanced colorectal adenomas have an increased prevalence of colorectal cancer.

BACKGROUND & AIMS: The risk of colorectal cancer in relatives of patients with adenomatous colonic polyps is not well defined. This study assessed whether finding colonic neoplasia during screening colonoscopy was related to the family history of colorectal cancer among the participants' parents and siblings. METHODS: Self-reported family history of colorectal cancer was recorded for all participants in a screening colonoscopy study. The size and location of all polyps were recorded before their removal and histologic examination. Participants were grouped according to the most advanced lesion detected. RESULTS: Three thousand one hundred twenty-one patients underwent complete colonoscopic examination. Subjects with adenomas were more likely to have a family history of colorectal cancer than were subjects without polyps (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.09-1.70). The finding of a small (<1 cm) tubular adenoma as the most advanced lesion was associated with only a modest increase in the OR of colorectal cancer in family members (OR, 1.26; 95% CI, 0.99-1.61), but the presence of an advanced adenoma was associated with a higher OR (OR, 1.62;5% CI, 1.16-2.26). Younger age of adenoma diagnosis was not related to a higher prevalence of a family history of colorectal cancer. CONCLUSIONS: Relatives patients with advanced colorectal adenomas have an increased risk of colorectal cancer. Individuals with advanced colorectal adenomas should be counseled about the increased risk of colorectal cancer among their relatives.     

Risk of malignant disease among 1525 adult male US Veterans with Gaucher disease

BACKGROUND: Some, but not all, reports suggest that patients with Gaucher disease are at increased risk of developing malignancies, particularly hematopoietic tumors. The aim of this study was to assess the pattern of Gaucher disease and subsequent malignancies among male veterans admitted to US Veterans Affairs hospitals. METHODS: Among 832 294 African American and 3 668 983 white male veterans with at least 1 hospital admission in US Veterans Affairs hospitals and up to 27 years of follow-up, we identified a total of 1525 patients with Gaucher disease; 11.7% were African Americans. We used Poisson regression methods for cohort data to estimate relative risks (RRs) and 95% confidence intervals (CIs) after adjusting for attained age and calendar year, race, number of hospital visits, and latency. RESULTS: When patients with Gaucher disease were compared with patients without Gaucher disease, the RR of any cancer was 0.91 (95% CI, 0.76-1.08 [n = 137]). When we stratified our analyses by race, risks were similar for whites (RR, 0.89; 95% CI, 0.74-1.07 [n = 120]) and African Americans (RR, 1.00; 95% CI, 0.61-1.64 [ n = 17]). Patients with Gaucher disease had an elevated risk for non-Hodgkin lymphoma (RR, 2.54; 95% CI, 1.32-4.88 [n = 9]), malignant melanoma (RR, 3.07; 95% CI, 1.28-7.38 [n = 5]), and pancreatic cancer (RR, 2.37; 95% CI, 1.13-4.98 [n = 7]). Among the remaining 19 cases involving defined solid tumors and 7 other hematologic malignancies, we found no statistical association with Gaucher disease. CONCLUSION: We found 2- to 3-fold risks of non-Hodgkin lymphoma, malignant melanoma, and pancreatic cancer in patients with Gaucher disease, but no significant association between Gaucher disease and cancer in general or with other specific malignancies such as multiple myeloma.     

Cholecystectomy and the Risk of Colorectal Adenomas

Cholecystectomy has been identified as a risk factor for colorectal cancer, yet little attention has been given to the relationship between cholecystectomy and colorectal adenomas. Utilizing data collected in two large cross-sectional studies of colorectal adenoma risk factors, we examined the association between cholecystectomy and colorectal adenomas. In the adjusted logistic regression model, both men and women showed no effect of cholecystectomy on risk of colorectal adenomas (men: OR 0.67 [95% CI 0.30–1.47]; women: OR 1.46 [95% CI 0.92–2.29]). No effect was seen when examining the time since cholecystectomy for men. There was a slight association found for women who had a cholecystectomy less than 10 years prior (OR 2.02 [95% CI 1.06–3.87]) but no association was seen in women with cholecystectomy at least 10 years prior (OR 1.14 [95% CI 0.62–2.09]). Thus, we conclude that, although cholecystectomy is a risk factor for colorectal cancer, cholecystectomy is not a risk factor for colorectal adenomas.     

Prevalence of colorectal neoplasia in smokers

OBJECTIVES: Smoking has been linked with colorectal neoplasia. Previous colonoscopy screening studies have omitted smoking and have examined only gender, age, and family history. Our aim was to use a screening population to measure the prevalence of neoplasia in smokers, the anatomic location of these lesions, and the strength of this association relative to other risk factors. METHODS: Data collected from the charts of 1988 screening colonoscopy patients included colonic findings, histology, risk factors for colorectal neoplasia, and smoking pattern. Current smokers were defined as those who had smoked more than 10 pack-years and were currently smoking or who had quit within the past 10 yr. Our outcomes were any adenomatous lesion and significant colonic neoplasia, which included adenocarcinoma, high grade dysplasia, villous tissue, large (>1 cm) adenomas, and multiple (more than two) adenomas. RESULTS: Multivariate analysis revealed that current smokers were more likely to have any adenomatous lesion (odds ratio [OR] = 1.89; 95% CI = 1.42-2.51; p < 0.001) as well as significant neoplasia (OR = 2.26; 95% CI = 1.56-3.27; p < 0.001) than those who had never smoked. The increased risk for smokers was predominantly for left-sided neoplasia. The risk for significant neoplasia was greater for smokers than for patients with a family history of colorectal cancer (OR = 1.20; 95% CI = 0.75-1.92; p > 0.05). CONCLUSIONS: Smoking is a significant risk factor for colorectal neoplasia in a screening population, especially for significant left-sided lesions. In our sample population, smoking posed a greater risk than family history of colorectal cancer.     

Prevalence and risk of colorectal neoplasia in consumers of alcohol in a screening population

BACKGROUND AND AIMS: Although studies suggest a positive association between alcohol consumption and risk for colorectal neoplasia, the impact on screening has not been fully examined. It is also unclear whether all types of alcohol are associated with an increased risk. We performed a cross-sectional study to examine the impact of regular alcohol consumption on the detection of significant colorectal neoplasia in a screening population. METHODS: Data collected for 2,291 patients presenting for screening colonoscopy: known risk factors for colorectal neoplasia and alcohol drinking pattern. Our outcome was the endoscopic detection of significant colorectal neoplasia, which included adenocarcinoma, high-grade dysplasia, villous tissue, adenomas 1 cm or greater and multiple (>2) adenomas of any size. RESULTS: When compared to abstainers, we found an increased risk for significant neoplasia in those patients who consumed more than eight drinks of spirits alcohol (26.3%; OR = 2.53; 95% CI = 1.10-4.28; p < 0.01) and those who drank more than eight servings of beer per week (21.7%; OR = 2.43; 95% CI = 1.11-5.32; p= 0.02). Consuming one to eight glasses of wine per week was associated with a decreased risk for significant neoplasia (OR = 0.55; 95% CI = 0.34-0.87; p < 0.01). CONCLUSIONS: While there was a more than twofold increased risk of significant colorectal neoplasia in people who drink spirits and beer, people who drank wine had a lower risk. In our sample, people who drank more than eight servings of beer or spirits per week had at least a one in five chance of having significant colorectal neoplasia detected by screening colonoscopy.     

Predictive and protective factors associated with colorectal cancer in ulcerative colitis: A case-control study

BACKGROUND & AIMS: Predictive and protective factors associated with colorectal cancer in chronic ulcerative colitis are not well described. Surveillance colonoscopy and 5-aminosalicylic acid therapy may mitigate cancer risk, but there is debate because these variables have not been evaluated in the same study. The presence of postinflammatory pseudopolyps and use of other anti-inflammatory medications may be important variables that influence risk, but data are sparse. METHODS: Variables associated with colorectal cancer were registered in 188 patients with ulcerative colitis-related cancer and matched controls. Conditional logistic regression, adjusted for age at colitis diagnosis and colitis duration, identified a final set of variables independently associated with colorectal cancer. RESULTS: In the final multiple variable model, the most important factors associated with colorectal cancer were a history of pseudopolyps (OR, 2.5; 95% CI: 1.4-4.6), 1 or 2 surveillance colonoscopies (OR, 0.4; 95% CI: 0.2-0.7), smoking (OR, 0.5; 95% CI: 0.2-0.9) and use of corticosteroids (OR, 0.4; 95% CI: 0.2-0.8), aspirin (OR, 0.3; 95% CI: 0.1-0.8), nonsteroidal anti-inflammatory drugs (OR, 0.1; 95% CI: 0.03-0.5), and 5-aminosalicylic acid agents (OR, 0.4; 95% CI: 0.2-0.9), although the latter was not statistically significant after 5 years. Primary sclerosing cholangitis and immunosuppressive use were not statistically significant. CONCLUSIONS: These results suggest that, in a population matched for extent and duration of chronic ulcerative colitis, surveillance colonoscopy and use of anti-inflammatory medications may reduce the risk of colorectal cancer. A history of postinflammatory pseudopolyps appears to be a predictive factor for cancer.