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Robert S Sandler

Publications and source records attributed to Robert S Sandler.

At least 19 recordsLinked to original sources
PubMed2007

Calcium, dietary, and lifestyle factors in the prevention of colorectal adenomas.

BACKGROUND: Many studies have suggested a role for calcium in reducing the risk of colorectal adenomas and cancer but its effectiveness may be dependent on interactions with other dietary and/or lifestyle factors. We examined the association between calcium and prevalence of adenomas and assessed whether the association was stronger in biologically plausible subgroups. METHODS: Cross-sectional data from 222 cases and 479 adenoma-free controls who underwent colonoscopies and completed food frequency and lifestyle questionnaires were used in the analyses. Multivariable logistic regression was used to estimate the association between calcium and prevalence of adenomas. Stratified analyses and the likelihood ratio test were used to examine effect modification by various demographic, lifestyle, and behavioral factors. RESULTS: Overall, little association was observed comparing total calcium intake of > or = 900 mg/day to < 500 mg/day (adjusted odds ratio [OR] = 0.85, 95% confidence interval [CI]: 0.53-1.37). However, stronger associations were observed in patients with lower fat intake and in those who regularly (> or = 15 times/month) took nonsteroidal antiinflammatory drugs (NSAIDs). Specifically, total calcium intake of > or = 900 mg/day was associated with a lower prevalence of adenomas among patients with lower fat intake (OR = 0.47, 95% CI: 0.25-0.91) but not among those with higher fat intake (OR = 1.20, 95% CI: 0.61-2.35; P-value for interaction = .01). For NSAIDs, the associations were OR = 0.37 (95% CI: 0.16-0.86) for regular NSAID users and OR = 1.27 (95% CI: 0.73-2.22) with infrequent or nonuse of NSAIDs, respectively (P = .06). CONCLUSIONS: The data suggest that a lower-fat diet and regular NSAID use may enhance calcium's effectiveness as a colorectal cancer preventive agent.

Adenoma↗
PubMed2007

Prolonged effect of calcium supplementation on risk of colorectal adenomas in a randomized trial.

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.

Adenoma↗
PubMed2007

Inflammatory bowel disease is not a risk factor for cardiovascular disease mortality: results from a systematic review and meta-analysis.

OBJECTIVES: Inflammation in general, and C-reactive protein (CRP) in particular, are closely associated with atherosclerosis. Similarly, the risk of cardiovascular (CV) disease is increased in several systemic inflammatory diseases. The purpose of this study was to examine whether inflammatory bowel disease (IBD) increases CV mortality, an indirect surrogate for CV disease incidence. METHODS: A systematic review of studies on CV mortality rates in patients with IBD published between 1965 and 2006 was performed. Studies were included for analysis if they reported data on CV-disease-specific standardized mortality ratios (SMRs) for Crohn's disease (CD) and/or ulcerative colitis (UC). A meta-analysis of SMRs from included studies was performed. RESULTS: The review ultimately included 11 studies. Overall there were 4,532 patients with CD and 9,533 patients with UC. SMR point estimates ranged from 0.7 to 1.5 for patients with CD and 0.6-1.1 for patients with UC. There was not a statistically significant increase in CV SMR for either CD or UC in any study. However, two studies demonstrated a statistically significant decrease in CV SMR for UC. Finally, the meta-SMR for CD was 1.0 (95% CI 0.8-1.1) and the meta-SMR for UC was 0.9 (95% CI 0.8-1.0). CONCLUSIONS: IBD is not associated with increased CV mortality. Although CV mortality is a suboptimal surrogate for CV disease incidence, this finding provides indirect evidence against an association between IBD and CV disease.

Cardiovascular Diseases↗
PubMed2006

Ornithine decarboxylase polymorphism modification of response to aspirin treatment for colorectal adenoma prevention.

BACKGROUND: Previous research suggests that the G315A single-nucleotide polymorphism in the ornithine decarboxylase (ODC) gene may be a genetic marker for risk of colorectal neoplasia and may also modify the association of aspirin use with risk. METHODS: We tested these hypotheses among participants in the Aspirin/Folate Polyp Prevention Study who were randomly assigned to placebo or to aspirin treatment (81 or 325 mg daily) and followed for 3 years for the occurrence of new adenomas. Genomic DNA from 973 subjects was analyzed for ODC genotype. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated to test the association between ODC genotype and adenoma occurrence and interactions with aspirin treatment. All statistical tests were two-sided. RESULTS: Of the 973 subjects, 54% were homozygous wild-type (GG), 7% were homozygous variant (AA), and 39% were heterozygous individuals; the allele frequencies varied statistically significantly by race and ethnicity. Among these subjects, the absolute risk of any adenoma was 45% and the risk of an advanced lesion was 10%. Overall, no association was found between ODC genotype and the occurrence of new adenomas, but genotype did modify the effect of aspirin on adenoma risk. Although aspirin treatment had no protective effect among subjects with a GG genotype, among subjects with at least one A allele, it was associated with statistically significant reduced risks of any adenoma (RR = 0.77, 95% CI = 0.63 to 0.95; P = .02, P(interaction) = .04) and of advanced lesions (RR = 0.51, 95% CI = 0.29 to 0.90; P = .02, P(interaction) = .02). Among subjects with at least one A allele, 40.8% who took aspirin versus 52.9% who took placebo developed adenomas; 7.1% versus 14.0% developed advanced lesions. CONCLUSION: ODC genotype may modify the response to aspirin treatment for colorectal adenoma prevention.

Adenoma↗
PubMed2006

A randomized trial of rofecoxib for the chemoprevention of colorectal adenomas.

BACKGROUND & AIMS: In human and animal studies, nonsteroidal anti-inflammatory drugs have been associated with a reduced risk of colorectal neoplasia. Although the underlying mechanisms are unknown, inhibition of cyclooxygenase (COX), particularly COX-2, is thought to play a role. We conducted a randomized, placebo-controlled, double-blind trial to assess whether use of the selective COX-2 inhibitor rofecoxib would reduce the risk of colorectal adenomas. METHODS: We randomized 2587 subjects with a recent history of histologically confirmed adenomas to receive daily placebo or 25 mg rofecoxib. Randomization was stratified by baseline use of cardioprotective aspirin. Colonoscopic follow-up evaluation was planned for 1 and 3 years after randomization. The primary end point was all adenomas diagnosed during 3 years' treatment. In a modified intent-to-treat analysis, we computed the relative risk of any adenoma after randomization, using Mantel-Haenszel statistics stratified by low-dose aspirin use at baseline. RESULTS: Adenoma recurrence was less frequent for rofecoxib subjects than for those randomized to placebo (41% vs 55%; P < .0001; relative risk [RR], 0.76; 95% confidence interval [CI], 0.69-0.83). Rofecoxib also conferred a reduction in risk of advanced adenomas (P < .01). The chemopreventive effect was more pronounced in the first year (RR, 0.65; 95% CI, 0.57-0.73) than in the subsequent 2 years (RR, 0.81; 95% CI, 0.71-0.93). As reported previously, rofecoxib was associated with increased risks of significant upper gastrointestinal events and serious thrombotic cardiovascular events. CONCLUSIONS: In this randomized trial, rofecoxib significantly reduced the risk of colorectal adenomas, but also had serious toxicity.

Adenoma↗
PubMed2006

The burden of gastrointestinal and liver diseases, 2006.

BACKGROUND: Digestive and liver diseases are a source of significant morbidity, mortality, and health-care costs for the U.S. population. An annual report of the toll of these diseases could be helpful to clinicians, policymakers, and researchers. AIM: To describe the epidemiology of gastrointestinal and liver diseases in the United States using data from privately and publicly held databases. METHODS: We collected data from the National Center for Health Statistics, the National Ambulatory Medical Care Survey, the National Inpatient Sample, the Centers for Disease Control and Prevention, and the National Cancer Institute, as well as proprietary pharmaceutical databases to construct a report on the impact of gastrointestinal and liver diseases on the U.S. population. We compiled information on causes of death, hospitalization, clinic visits, cancer incidence, and mortality and infectious disease incidence from these databases, and extracted data specific to gastrointestinal diseases. Because of the high costs associated with medications used to treat gastrointestinal diseases, we also include in this year's report a special section on pharmacoepidemiology and pharmacoeconomics. RESULTS: Colorectal cancer continues to be the leading cause of GI-related death, although the data indicate a downward trend in deaths. Abdominal pain, diarrhea, vomiting, and nausea are the most common GI symptoms precipitating a visit to the physician, and GERD is the most common GI-related diagnosis given in office visits. Chest pain not specified to be cardiac in origin is the most common cause of inpatient admission possibly related to GI disease, with cholelithiasis and pancreatitis following. Americans spend in excess of US dollars 10 billion/yr on proton pump inhibitors (PPIs), and two of the top five selling drugs in the United States are PPIs. Trends in PPI use demonstrate turbulent changes, likely reflecting both new drug entries into the field, as well as drug marketing. The number of PPI prescriptions/yr in the United States has doubled since 1999. Twenty-three drugs used for gastrointestinal diseases are among the top 200 generic drugs used in the United States. CONCLUSIONS: Gastrointestinal and liver diseases are significant contributors to the morbidity, mortality, and health-care expenditures of the U.S. population.

Female↗
PubMed2006

Gastric cancer and the high combination prevalence of host cytokine genotypes and Helicobacter pylori in Honduras.

BACKGROUND & AIMS: Inflammatory cytokine polymorphisms are associated with gastric adenocarcinoma in Helicobacter pylori-infected patients in Europe and Asia. We investigated the cytokine profile in the Latino population, specifically Honduras, a high-incidence region, and the use of the combination prevalence of H pylori and genotypes in identifying high-risk populations. METHODS: A population-based case-control study identified 170 incident gastric cancer cases and 162 healthy village controls. Interleukin (IL)-Ibeta-511, IL-1RN, IL-10-1082, and tumor necrosis factor-alpha-308 genotypes were determined. We define the combination prevalence index (CPI) as the product of H pylori and IL-1beta-511T+ genotype prevalence in healthy subjects. Medline identified gastric cancer studies to facilitate country-specific CPI calculations. RESULTS: In healthy, population-based Honduran controls, IL-1beta-511T+ prevalence was 81% (95% confidence interval, 75%-87%; CT, 57%; TT, 25%), which was among the highest reported. IL-10-1082A+ prevalence was 93% (95% confidence interval, 88%-97%), mirroring Asian populations. Seventeen percent were homozygous for both proinflammatory cytokines (TT/AA), with increased risk among cases (odds ratio, 2.6; 95% confidence intervals, 1.0-6.8). Tumor necrosis factor-alpha polymorphisms were nearly absent. Endemic H pylori infection (85%) was confirmed. Importantly, the CPI association with country incidence is highly significant (P = .0057), based on 16 global populations and Honduras. Sensitivity analysis confirms a robust CPI. CONCLUSIONS: The CPI, based on IL-1beta genotypes, has a strong association with country-specific gastric cancer incidence. The CPI correlation supports the chronic inflammation carcinogenesis model, and may explain the geographic variation. We report a novel cytokine profile in Honduras that mirrors Asian populations and explains the high incidence rates. This may have dyspepsia management and screening implications for the growing US Latino population.

Adult↗
PubMed2006

Influence of target gene mutations on survival, stage and histology in sporadic microsatellite unstable colon cancers.

High-frequency microsatellite unstable (MSI-H) colon tumors develop as a consequence of mutations at repetitive sequences in target genes. TGFBR2 and ACVR2, encoding TGFbeta superfamily receptors, and the proapoptotic gene BAX are frequent targets for frameshift mutation. We analyzed the effect of these mutations on survival and histology in 2 separate cohorts. Forty-eight MSI-H Dukes B2 colon tumors from a cohort of 172 patients had mutations in TGFBR2, BAX and ACVR2 correlated with patient survival. Further, 54 population-based MSI-H colon cancers of all stages from a cohort of 503 patients had mutations correlated with tumor stage, grade and size. Of 44 amplifiable MSI-H Dukes B2 tumors, 70% harbored TGFBR2, 63% BAX and only 4.5% ACVR2 mutations. While mutation alone did not influence survival, concomitant mutation of TGFBR2 and BAX was associated with an improved prognosis in Dukes B2 patients (p=0.05). ACVR2 mutations were more frequent in the second, population-based cohort (stage II: 32.5%, p<0.05). While no target gene mutation correlated with stage in this cohort, poor histological grade and large tumor volume were associated with mutant ACVR2, but not TGFBR2 or BAX mutations, and likely accounts for the lower prevalence of ACVR2 mutations in the first, well-differentiated Dukes B2 cohort. Because target gene mutations did not correlate with stage, they likely occur early in the pathogenesis of MSI-H cancers. Mutations in TGFBR2 and BAX may improve survival in MSI-H Dukes B2 patients, and mutations of ACVR2 may augment histological changes consistent with poor tumor grade that is characteristic of MSI-H colon cancers, and increase tumor size.

Activin Receptors, Type II↗
PubMed2006

Research recruitment through US central cancer registries: balancing privacy and scientific issues.

Cancer registries are a valuable resource for recruiting participants for public health-oriented research, although such recruitment raises potentially competing concerns about patient privacy and participant accrual. We surveyed US central cancer registries about their policies for research contact with patients, and results showed substantial variation. The strategy used most frequently (37.5% of those that allowed patient contact), which was among the least restrictive, was for investigators to notify patients' physicians and then contact patients with an opt-out approach. The most restrictive strategy was for registry staff to obtain physician permission and contact patients with an opt-in approach. Population-based studies enhance cancer control efforts, and registry policies can affect researchers' ability to conduct such studies. Further discussion about balanced recruitment approaches that protect patient privacy and encourage beneficial research is needed.

Certification↗
PubMed2006

COX-2 polymorphism, use of nonsteroidal anti-inflammatory drugs, and risk of colon cancer in African Americans (United States).

INTRODUCTION: The inducible Cyclooxygenase (COX)-2 enzyme plays an important role in inflammation and carcinogenesis. Recent reports suggest that single nucleotide polymorphisms (SNPs) in the COX-2 gene may alter enzyme function and in turn modify an individual's risk of colon cancer. We explored the association between the COX-2 Val511Ala SNP and risk of colon cancer among 240 African American cases and 326 African American controls in a population-based, case-control study in North Carolina. METHODS: We used unconditional logistic regression models to determine the odds ratios (ORs) for genotype and risk of colon cancer. RESULTS: We observed a non-statistically significant inverse association between any Ala COX-2 genotype and risk of colon cancer (OR = 0.62, 95% CI: 0.33, 1.16) among African Americans. The inverse association was present among non-regular NSAID users, use < or = 3 times/week, (OR = 0.66; 95% CI: 0.32, 1.37) and regular NSAID users, use > or =3 times/week for > or =3 months, (OR = 0.41; 95% CI: 0.11, 1.54). CONCLUSIONS: Our results suggest that the COX-2 Val511Ala SNP does not antagonize the effect of NSAIDs on colon cancer risk and provides support that NSAID use and the COX-2 Val511Ala SNP may contribute to a reduced risk of colon cancer among African Americans.

Black or African American↗
PubMed2006

GSTM1 and GSTT1 polymorphisms, cigarette smoking, and risk of colon cancer: a population-based case-control study in North Carolina (United States).

Cigarette smoke is a risk factor for colon cancer, but the importance of dose and interaction with genetic susceptibility remain poorly understood. We used data from a population-based case control study, to examine the association between cigarette smoking and colon cancer in African Americans and whites, and colon cancer and polymorphisms in GSTM1 and GSTT1. A total of 554 cases of primary colon cancer and 874 controls were included in this analysis. We found no association between cigarette smoking (ever versus never) and colon cancer in African Americans (odds ratio (OR)=0.93, 95% confidence interval (CI)=0.65-1.33). In contrast, there was an increased risk of cigarette smoking in whites (OR=1.43, CI=1.05-1.94). There was a small increased risk of colon cancer for individuals with GSTM1 null (African Americans, OR=1.43, CI, 0.98-2.09; whites, OR=1.19, CI, 0.90-1.58) and a decreased risk of colon cancer for individuals with GSTT1 null (African Americans, OR=0.59, CI: 0.40-0.86; whites, OR=0.72, CI: 0.53-1.00). There were weak interactions between GSTT1 null and cigarette smoking in whites, and GSTM1 null genotype and cigarette smoking in African Americans. GSTT1 and GSTM1 polymorphisms may be weakly related to colon cancer risk and there may be racial differences in gene-smoking interactions.

Adult↗
PubMed2006

The effect of physician permission versus notification on research recruitment through cancer registries (United States).

OBJECTIVE: To determine how physicians responded when investigators inquired about contacting patients identified through a central cancer registry, and to examine participation rates under physician permission versus notification approaches. METHODS: We analyzed existing data from seven observational epidemiologic studies conducted in North Carolina between 1993 and 2004, capitalizing on a 'natural experiment' that arose when the state registry changed from a policy requiring investigators to obtain physician permission to one requiring only physician notification. RESULTS: When a notification approach was used, physicians approved researcher contact with a higher proportion of patients, and a higher proportion of physicians approved contact with or provided eligibility information about all patients requested, compared with a permission approach. Among physicians who were contacted under both approaches, the proportion of patients for whom they approved contact or provided information was significantly higher when they were notified. Physician notification was also associated with higher patient contact and overall response rates. Patient cooperation rates did not differ between the two approaches, suggesting that patients did not respond negatively to the fact that their physician was not explicitly asked to provide permission. CONCLUSION: Notification is likely an efficient way of involving patients' physicians, providing opportunity for physician input but avoiding the burdens associated with requiring their permission.

Clinical Trials as Topic↗
PubMed2006

Aspirin may be more effective in preventing colorectal adenomas in patients with higher BMI (United States).

Obesity is a risk factor for colon cancer, possibly due to elevated levels of circulating cytokines derived from adipose tissue. Aspirin, which may affect the levels of these cytokines, has been shown in randomized controlled trials to decrease the risk of colorectal adenomas. We hypothesized that the chemopreventive effect of aspirin might be greater in individuals with higher body mass index (BMI). Data were available from the Aspirin/Folate Polyp Prevention Study, a randomized controlled trial of aspirin and folic acid to prevent recurrent colorectal adenomas. Obesity was defined as BMI > or = 30 (kg/m2), overweight as BMI of 25-29 (kg/m2) and normal weight as BMI <25 (kg/m2). For the analysis of the effect of aspirin on the recurrence of colorectal adenoma by BMI, we computed risk ratios for aspirin versus placebo within the three BMI strata using a modified Poisson model. Overall the risk reduction of adenomas with a daily dose of 325 mg aspirin was greater among subjects with higher BMI. Among obese subjects the risk ratio (RR) for advanced adenomas compared with placebo was 0.44 (95% CI 0.17-1.10), versus RR = 1.23 (95% CI 0.55-2.77) among those with normal weight. However, 81 mg aspirin daily did not interact with BMI to modify the risk of adenomas in such a fashion. The more pronounced effect of 325 mg aspirin in individuals with higher BMI suggests a possible protective role of anti-inflammatory aspirin against increased adipose-driven cytokines among obese subjects.

Adenomatous Polyps↗
PubMed2006

Rural-urban differences in colon cancer risk in blacks and whites: the North Carolina Colon Cancer Study.

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.

Black or African American↗