Previous Colorectal Adenoma Research Articles

The predictive value of small versus diminutive adenomas for subsequent advanced neoplasia

Patients with previous colorectal adenomas are at increased risk of colorectal cancer. Current guidelines for postpolypectomy surveillance intervals treat all tubular adenomas 1 to 9mm in size with low-grade dysplasia as carrying the same level of risk. We evaluated whether 6 to 9mm adenomas detected at colonoscopy are associated with greater risk of advanced neoplasia at follow-up compared with baseline 1 to 5mm adenomas. We retrospectively evaluated a colonoscopy database at a single U.S. academic center. Patients with baseline examinations demonstrating tubular adenomas 1 to 9mm in size with low-grade dysplasia and no advanced adenomas were included. Follow-up colonoscopies were performed at least 200 days later and were assessed for incident advanced neoplasia (cancer, high-grade dysplasia, adenoma≥10mm in size, or villous elements). There were 2477 qualifying baseline colonoscopies. The absolute risk of metachronous advanced neoplasia increased from 3.6% in patients with 1 to 5mm adenomas to 6.9% in patients with at least 1 adenoma of 6 to 9mm (P= .001). Patients with 5 or more adenomas 1 of which was at least 6 to 9mm had the highest risk of advanced neoplasia at follow-up (10.4%, P= .006). When only screening colonoscopies were considered, all baseline groups (1-2 adenomas, 3-4 adenomas,≥5 adenomas) with adenomas 6 to 9mm in size had an increased risk for metachronous advanced neoplasia (odds ratio [OR], 4.07; 95% confidence interval [CI], 1.50-11.04; OR, 4.91; 95% CI, 1.44-16.75; OR, 4.71; 95% CI, 1.30-17.05, respectively). Patients with baseline small (6-9mm) adenomas have an increased risk of advanced lesions on follow-up compared with patients with only diminutive (1-5mm) adenomas. Postpolypectomy guidelines should consider risk stratification based on small versus diminutive adenomas.

Effect of chromoendoscopy in the proximal colon on colorectal neoplasia detection in Lynch syndrome: a multicenter randomized controlled trial

Patients with Lynch syndrome (LS) undergo regular surveillance by colonoscopy because of an increased risk of colorectal neoplasia, particularly in the proximal colon. Chromoendoscopy (CE) has been reported to improve neoplasia detection compared with conventional white-light endoscopy (WLE), but evidence is limited. Our aim was to investigate the effect of CE in the proximal colon on detection of neoplastic lesions during surveillance in LS. This was a multicenter prospective randomized controlled trial of 246 patients with LS who were randomly assigned (1:1) to conventional WLE (n= 123) or colonoscopy with CE in the proximal colon (n= 123), stratified for previous colorectal adenomas and enrolling center. Two years after baseline colonoscopy, patients underwent colonoscopy with CE in the proximal colon. The primary outcome was the proportion of patients with at least one neoplastic lesion at baseline and after 2 years. Neoplasia detection rates at baseline colonoscopy were 27% for WLE versus 30% for CE (odds ratio [OR], 1.23; 95% confidence interval [CI], 0.69-2.2; P= .56). In the proximal colon, neoplasia detection rates were 16% for WLE versus 24% for CE (OR, 1.6; 95% CI, 0.9-3.1; P= .13). Total procedure time was 9 minutes longer in the CE group. At follow-up after 2 years, neoplasia detection rates were similar in both groups: 26% for the original WLE group versus 28% for the CE group (OR, 1.1; P= .81). CE in the proximal colon for LS surveillance was not superior to WLE with respect to the initial detection of neoplasia, and not associated with reduced neoplasia detection rates after 2 years. The value of CE remains to be established. (Clinical trial registration number: NCT00905710.).

Abstract 3266: Measurement and comparison of the gut microbial communities in fecal, rectal swab, and mucosal samples

Abstract Background: Studies evaluating the gut microbiome frequently use stool. However, stool, which is predominantly composed of luminal bacteria, may not adequately reflect mucosally adherent bacteria. The purpose of this study is to evaluate similarities and differences in gut bacterial measurements and stability in the microbial communities of three different types of samples that could be used to assess different niches of the gut microbiome: rectal swab, stool, and normal rectal mucosa samples. Design: Sixty-eight participants were selected from a personalized chemoprevention trial population of individuals with previous colorectal adenomas who had donated stool, swab, and mucosal samples at baseline and three months later. 16S rRNA amplicon sequencing was conducted for 60 participants at two time points (n=120 stool and 120 swab). Whole-genome shotgun metagenomics DNA sequencing was conducted for 50 participants at two time points (n=100 stool, 28 swab, and 16 mucosal). Results: In swab-stool comparisons, there were substantial taxa differences with some taxa varying largely by sample type (e.g., Thermaceae) while other taxa were predominantly associated with interindividual subject variation (e.g., Desulfovibrionaceae) or by both sample type and participant (e.g., Enterobacteriaceae). At species-level resolution (with WGS sequences) we observed that bacteria associated with colorectal tumors (Escherichia coli and Fusobacterium nucleatum) were of higher relative abundance in swab than stool. There were also statistically significant differences in other bacteria according to the sample type (e.g., Bifidobacterium longum, Bacteroides fragilis). Comparing all three sample types with whole-genome metagenome shotgun sequencing, swab samples were much closer to stool samples than mucosa samples, although all KEGG functional Level 1 and Level 2 pathways were significantly different across all sample types (e.g., transcription and environmental adaptation). However, the individual signature of participants was also observed and was largely stable between two time points. Thus, we found that while the distribution of some taxa was associated with these different sampling techniques, other taxa largely reflected individual differences in the microbial community that were insensitive to sampling technique. Conclusion: There is substantial variability in the assessment of the gut microbial community according to the type of sample. Citation Format: Roshonda B Jones, Xiangzhu Zhu, Emili Moan, Harvey J. Murff, Qi Dai, Martha J. Shrubsole, Anthony A. Fodor, M. Andrea Azcarate-Peril, Reid M. Ness, Douglas L. Seidner. Measurement and comparison of the gut microbial communities in fecal, rectal swab, and mucosal samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3266.

The effect of metformin on the recurrence of colorectal adenoma in diabetic patients with previous colorectal adenoma

Existing studies suggest that metformin lowers the risk and mortality of colorectal cancer. However, the effect of metformin on the suppression and prevention of colorectal adenomas is not clear. The aim of this study was to evaluate the effect of metformin on the recurrence of colorectal adenoma in diabetic patients with previous colorectal adenoma. Among 423 diabetic patients who underwent surveillance colonoscopy after resection of colorectal adenoma between 2005 and 2011, 257 patients were retrospectively reviewed. The patients were divided into two groups: one group comprising 106 patients who took metformin and another group comprising 151 patients who did not take metformin. The clinical characteristics, colorectal adenoma recurrence, and valuable factors for adenoma recurrence were analyzed. At surveillance colonoscopy after colonoscopic polypectomy for adenoma, 38 patients (35.8%) exhibited colorectal adenoma among 106 patients who took metformin, compared with 85 patients (56.3%) with colorectal adenoma among 151 patients who did not take metformin (odds ratio 0.434, 95% confidence interval 0.260-0.723, P=0.001). Multivariate Cox analysis showed that metformin was associated with decreased recurrence of colorectal adenoma (hazard ratio 0.572, 95% confidence interval 0.385-0.852, P=0.006) in diabetic patients with previous colorectal adenoma. The cumulative probability of colorectal adenoma recurrence was significantly lower in the metformin group than in the non-metformin group (P=0.001). Metformin use in diabetic patients with previous colorectal adenoma is associated with a lower risk of colorectal adenoma recurrence.

Abstract 1758: Circulating insulin-like growth factors: Correlates and responses to calcium supplementation in colorectal adenoma patients

Abstract Insulin-like growth factor 1 (IGF-1) and its binding proteins are an important part of the IGF/growth hormone axis needed for normal growth and organ function. IGF-1 signaling has also been implicated in tumorigenesis with higher circulating levels of IGF-1 and the molar ratio of IGF-1 to IGF binding protein 3 (IGFBP-3) being directly associated with colorectal, breast, and prostate cancers, as well as with colorectal adenomas. IGF binding protein 2 (IGFBP-2) also appears to be overexpressed in colorectal and lung cancers and leukemias. Limited evidence suggests that various dietary and lifestyle factors may influence circulating levels of IGF-1, IGFBP-2, and IGFBP-3. Among these factors, calcium has been statistically significantly associated with IGF-1, IGFBP-2, and IGFBP-3, but its effects on them have not been tested in a clinical trial. To investigate the effects of supplemental calcium (1.0 or 2.0 g/day) on serum levels of IGF-1, IGFBP-2, and IGFBP-3, we analyzed samples from a randomized, double-blinded, placebo-controlled, dose-response clinical trial of patients with previous sporadic, colorectal adenoma. We also investigated associations of various risk factors with the growth factors at baseline. IGF-1 was measured using an enzyme-linked immunosorbent assay, and IGFBP-2 and IGFBP-3 were measured using quantitative Western ligand blot assays. We found no appreciable effects of calcium over the 4-month treatment period on IGF-1, IGFBP-2, and IGFBP-3. At baseline, lower levels of IGF-1 and IGFBP-3 were associated with being female (P = 0.02 and 0.01, respectively) or older (P = 0.02 and 0.02, respectively); the IGF-1/IGFBP-3 molar ratio was inversely associated with body mass index (BMI) (P = 0.04); and IGFBP-2 was directly associated with age (P = 0.002) but inversely associated with BMI (P < 0.0001). We calculated residuals of non-fat milk intake as a novel method of examining the non-calcium, non-fat component of milk, modeled after the energy adjustment residual method. These residuals were inversely associated with IGFBP-2 (P = 0.05) and directly associated with the IGF-1/IGFBP-3 molar ratio (P = 0.11). Overall, our results do not support that calcium supplementation can modulate circulating levels of IGF-1, IGFBP-2, or IGFBP-3 among patients with previous colorectal adenoma. However, our findings do suggest potential associations of these growth factors with established risk factors for colorectal cancer (age [inversely associated with IGF-1 and IGFBP-3, directly associated with IGFBP-2] and adiposity [inversely associated with IGFBP-2 and the IGF-1/IGFBP-3 molar ratio]). Finally, our results provide new evidence of potential associations of IGF-1, IGFBP-2, and IGFBP-3 with milk intake independent of its calcium and fat content. Citation Format: Caroline Um, Veronika Fedirko, Christine Höflich, W Dana Flanders, Roberd M. Bostick. Circulating insulin-like growth factors: Correlates and responses to calcium supplementation in colorectal adenoma patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1758.

Abstract 1791: Effects of calcium and vitamin D supplementation on circulating markers of inflammation

Abstract Chronic inflammation plays a major role in colon carcinogenesis. Recent evidence from experimental models suggests that vitamin D and calcium may reduce systemic inflammation and local inflammation in the colorectum, thus contributing to reducing risk for colorectal neoplasia. However, human experimental evidence to support these purported anti-inflammatory effects remains inconclusive, coming from very few, small, mainly short-term clinical studies with a variety of doses and administration regimens, with and without calcium supplementation in very different patient populations, and with a limited number of inflammatory biomarkers measured. To address this, we tested the effects of calcium (1.2 g/d) and/or vitamin D3 (1,000 IU/d) supplementation for 3 or 5 years on circulating pro- (IFNγ, TNFα, IL-6, IL-8, IL-12p40) and anti-inflammatory (IL-10) cytokines in 471 participants with previous colorectal adenoma in a recently completed, multi-center, randomized, double-blind, placebo-controlled, modified 2 × 2 factorial chemoprevention clinical trial (NCT00153816). The cytokines were measured in plasma using multiplex electrochemiluminescence detection-based immunoassays. Over a 3- or 5-year treatment period, we found no appreciable effects of calcium and/or vitamin D supplementation on pro-inflammatory cytokines (all P-values > 0.3). However, there was a suggestion that vitamin D may favorably modulate concentrations of IL-10, an anti-inflammatory cytokine. In the calcium, vitamin D, and calcium plus vitamin D groups, the relative increase vs. placebo in IL-10 from baseline to end of follow-up was 3% (P = 0.78), 15% (P = 0.15), 13% (P = 0.35). Our preliminary results indicate no considerable effects of calcium and vitamin D treatment on circulating pro-inflammatory cytokines, and might suggest that vitamin D may increase circulating levels of anti-inflammatory cytokine IL-10, which plays an important role in the Th2-type immune response. Citation Format: Veronika Fedirko, Julia Latash, Roberd M. Bostick, Elizabeth L. Barry, John A. Baron on behalf of Investigators in the PPS4 Study. Effects of calcium and vitamin D supplementation on circulating markers of inflammation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1791.

Effects of calcium supplementation on biomarkers of inflammation and oxidative stress in colorectal adenoma patients: a randomized controlled trial.

Inflammation and oxidative stress play important roles in colorectal carcinogenesis. There is strong evidence that calcium reduces risk for colorectal neoplasms, possibly through its ability to bind bile acids and prevent their colonic toxicity (which occurs via an oxidative mechanism and results in an inflammatory response). In a previously reported pilot, randomized, controlled trial among sporadic colorectal adenoma patients we found that those on 2.0 g/day of calcium, relative to those on placebo, had an estimated drop in a combined cytokine z-score of 48% (P = 0.18) over 6 months. To follow-up these promising preliminary findings, we tested the efficacy of two doses of supplemental calcium (1.0 or 2.0 g/day) relative to placebo on modulating circulating biomarkers of inflammation [C-reactive protein (CRP) and 10 cytokines] and oxidative stress (F2-isoprostanes) over a 4-month treatment period among 193 patients with previous sporadic, colorectal adenoma in a randomized, double-blinded, placebo-controlled clinical trial. The inflammation markers were measured in plasma using electrochemiluminescence detection-based immunoassays, and F2-isoprostanes were measured in plasma using gas chromatography-mass spectrometry. Over a 4-month treatment period, we found no appreciable effects of calcium on CRP, cytokines, or F2-isoprostanes (P > 0.4), overall or within strata of several major risk factors for colorectal carcinogenesis, such as body mass index and regular use of nonsteroidal anti-inflammatory drugs. Overall, our results provide no evidence that calcium supplementation favorably modulates concentrations of circulating biomarkers of inflammation or oxidative stress over 4 months among patients with a previous colorectal adenoma.

Abstract 938: Circulating biomarkers of gut barrier function: Correlates and responses to calcium supplementation among sporadic colorectal adenoma patients in a dose-response randomized controlled trial

Abstract Gut barrier dysfunction contributes to several gastrointestinal disorders, including inflammatory bowel diseases and colorectal cancer, but factors associated with intestinal hyperpermeability have rarely been assessed in human populations, and there is very limited clinical trial evidence on whether gut barrier function may be modified by dietary factors. To address these gaps, we 1) evaluated factors associated with baseline circulating biomarkers of gut barrier function, and 2) tested the effect of calcium on these biomarkers over a 4-month treatment period among patients with previous colorectal adenoma in a randomized, double-blinded, placebo-controlled clinical trial (n = 193). Patients were randomized to placebo (n = 66), 1.0 g calcium (n = 64), or 2.0 g calcium (n = 63) daily. Circulating levels of anti-flagellin and anti-lipopolysaccharide (LPS) immunoglobulins (Igs) as markers of colonic hyperpermeability were measured at baseline and at 4-month follow-up via ELISA. At baseline, mean levels of anti-flagellin and anti-LPS IgA but not IgG were higher among men and those with a larger body mass index (BMI), a larger waist circumference, and higher levels of plasma C-reactive protein. Mean anti-flagellin IgG levels were higher among those with higher proinflammatory cytokine scores. We did not observe effects of calcium on anti-flagellin or anti-LPS Igs: the relative change of a combined permeability score (defined as the sum of the optical densities of all biomarkers) from baseline to follow-up was 0.07 (95% confidence interval [CI] -0.13, 0.27) for each treatment group relative to the placebo group (p-values ≥ 0.5). Our results suggest that 1) men and those with a larger BMI or waist circumference may have greater gut permeability, 2) markers of gut permeability and systemic inflammation may be directly associated with one another, and 3) supplemental calcium administered for 4 months may not modify circulating levels of biomarkers of gut barrier function. Citation Format: Baiyu Yang, Roberd M. Bostick, Andrew T. Gewirtz, Hao Quang Tran, Veronika Fedirko. Circulating biomarkers of gut barrier function: Correlates and responses to calcium supplementation among sporadic colorectal adenoma patients in a dose-response randomized controlled trial. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 938. doi:10.1158/1538-7445.AM2015-938

Effects of Calcium and Vitamin D Supplementation on Markers of Colonic Permeability

Impaired gut barrier function contributes to inflammatory bowel diseases and colorectal carcinogenesis. Recent evidence from experimental models indicates that calcium and vitamin D may beneficially modulate colonic permeability; however, to date, there are no reported human studies that investigated this hypothesis. To address this, we tested the effects of calcium (1.2 g/d) and/or vitamin D3 (1,000 IU/d) supplementation for 3 or 5 years on circulating biomarkers of colonic hyperpermeability (anti‐flagellin and anti‐lipopolysaccharide immunoglobulins [Igs], IgA and IgG) in 175 participants with previous colorectal adenoma from a recently completed, multi‐center, randomized, double‐blind, placebo‐controlled, modified 2 x 2 factorial chemoprevention clinical trial (NCT00153816). Igs were measured in plasma via ELISA. The relative change in a combined permeability score (CPS, defined as the sum of the optical densities of all biomarkers) from baseline to follow‐up was ‐2%, 1%, and 4% in the calcium, calcium plus vitamin D, and vitamin D groups vs. placebo, respectively (all P‐values > 0.5). At baseline, the CPS was higher among men (P = 0.02) and the severely obese (BMI >35 kg/m2; P = 0.002). Our preliminary results indicate no effect of calcium and vitamin D treatment on markers of colonic permeability, and suggest that men and those who are obese may have greater gut permeability.

Chemoprevention of colorectal cancer with ursodeoxycholic acid: Pro

Colorectal cancer is the third and second most common cancer among men and women, respectively, in France. Interest in the chemoprevention of colorectal cancer has increased over the last two decades. Experimental data strongly suggest that ursodeoxycholic acid (UDCA) may have chemopreventative actions in colorectal cancer. UDCA is able to inhibit tumor development in azoxymethane and in dextran-related colitis models. In high-risk populations such as subjects with previous colorectal adenoma removal or inflammatory bowel disease, five out of 10 published studies suggested beneficial effects with UDCA on colonic carcinogenesis. In the azoxymethane model, UDCA inhibited tumor development by counteracting the tumor-promoting effects of secondary bile acids such as deoxycholic acid (DCA). The opposing effects of UDCA and DCA on lipid raft composition may be central to their effects on colonic tumorigenesis. Differential effects of DCA and UDCA on growth factor and inflammatory signals involved in colorectal carcinogenesis, such as epidermal growth factor receptor (EGFR) signaling and COX-2 expression, very likely mediate their opposing effects on colonic tumor promotion and tumor inhibition, respectively.

Do we need colonoscopy in patients with gastric adenomas? The risk of colorectal adenoma in patients with gastric adenomas

Gastric polyps are found frequently in various colonic polyposis syndromes. Genetic alterations of several genes occur in gastric adenomas and colorectal adenomas. However, it is unknown whether patients with gastric adenomas are at higher risk for colorectal adenomas. To investigate the prevalence rate of colorectal adenoma in patients with gastric adenomas and to determine the association between the presence of gastric adenomas and synchronous colorectal adenomas. A retrospective, cross-sectional, case-control study. Single center: Center for Health Promotion of Samsung Medical Center. This study involved 87 patients with gastric adenomas and 174 sex-matched and age-matched controls among 19,019 participants who underwent EGD and colonoscopy simultaneously or within 6 months of each other from January 2001 to December 2008 at the Center for Health Promotion of Samsung Medical Center. EGD and colonoscopy. The prevalence rate of colorectal adenoma in patients with gastric adenomas. The 87 gastric adenoma patients included 72 men and 15 women. Colorectal adenomas were identified in 42 (48.3%) of 87 cases and in 58 (33.3%) of 174 controls (P = .022). The prevalence of colorectal adenoma was significantly higher in the gastric adenoma group than in the control group. The mean size and number of colorectal adenomas were not significantly different between the two groups. The majority of colorectal adenomas were located in distal colonic segments in the gastric adenoma group in contrast with proximal colonic segments in the control group. Multivariate logistic regression analysis revealed that independent risk factors for colorectal adenoma were the presence of gastric adenomas (odds ratio [OR], .915; 95% confidence interval [CI], 1.044-3.513) and increasing age over 55 years (OR, 2.943; 95% CI, 1.558-5.560). Lack of data on previous colorectal adenomas and possible confounding factors such as hyperlipidemia or diabetes mellitus. The risk of colorectal adenoma increases significantly in patients with gastric adenomas and in patients over age 55. A screening colonoscopy may be necessary for patients with gastric adenomas to detect colorectal adenomas.

Folic Acid and Vitamin B-12 Supplementation Does Not Favorably Influence Uracil Incorporation and Promoter Methylation in Rectal Mucosa DNA of Subjects with Previous Colorectal Adenomas ,

Adequate folate availability is necessary to sustain normal DNA synthesis and normal patterns of DNA methylation and these features of DNA can be modified by methylenetetrahydrofolate reductase (MTHFR) C677T genotype. This study investigated the effect of MTHFR C677T genotype and daily supplementation with 5 mg folic acid and 1.25 mg vitamin B-12 on uracil misincorporation into DNA and promoter methylation. Subjects (n = 86) with a history of colorectal adenoma and MTHFR CC or TT genotype were randomly assigned to receive folic acid plus vitamin B-12 or placebo for 6 mo. Uracil misincorporation and promoter methylation of 6 tumor suppressor and DNA repair genes were assessed in DNA from rectal biopsies at baseline and after the intervention. The biomarkers did not differ between the treated group and the placebo group after 6 mo compared with baseline. The uracil concentration of DNA increased in the treated group (5.37 fmol/μg DNA, P = 0.02), whereas it did not change in the placebo group (P = 0.42). The change from baseline of 4.01 fmol uracil/μg DNA tended to differ between the groups (P = 0.16). An increase in promoter methylation tended to occur more often in the intervention group than in the placebo group (OR = 1.67; P = 0.08). This study suggests that supplementation with high doses of folic acid and vitamin B-12 may not favorably influence uracil incorporation and promoter methylation in subjects with previous colorectal adenomas. Because such alterations may potentially increase the risk of neoplastic transformation, more research is needed to fully define the consequences of these molecular alterations.

Prolonged Effect of Calcium Supplementation on Risk of Colorectal Adenomas in a Randomized Trial

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. 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. 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. 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.

Screening for early colorectal cancer.

There is now solid evidence from randomized trials suggesting that it is possible to reduce mortality from colorectal cancer by 15% to 25% by screening with fecal occult blood tests (FOBTs). The major benefit results from detection of early cancer in average-risk persons above 50 years of age who have a positive test followed by colonoscopy. However, it has to be demonstrated that the same acceptability can be reached in the general population as that obtained in trials. Many countries must establish a screening organization in a limited area to learn how satisfactory quality assurance can be obtained before a country-wide screening program is set up. So far, screening has not resulted in a reduced incidence of colorectal cancer in true population studies despite removal of two to three times as many possible precursors compared to controls. Cost-effectiveness will probably be as good as that known from screening for breast cancer with mammography and better than that for cervical cancer. However, the calculations are based on the unhydrated Hemoccult-II test in randomized trials. More sensitive methods would be attractive, but none has yet been evaluated properly in average-risk persons. There is no general agreement how to screen high risk groups such as patients with previous colorectal adenomas and carcinomas, one or two first-degree relatives with colorectal neoplasia, or ulcerative colitis. Families with familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer, however, are presented with firm guidelines. Genetic screening has been helpful in no more than these two small groups in the colorectal carcinoma universe.