Risk Of Adenoma Recurrence Research Articles

Do interleukin polymorphisms play a role in the prevention of colorectal adenoma recurrence by dietary flavonols?

Chemopreventive dietary compounds, such as flavonols, may inhibit colorectal carcinogenesis partly by altering cytokine expression and attenuating inflammation. Single nucleotide polymorphisms (SNPs) in the promoter regions of genes encoding cytokines may influence flavonol-induced changes in cytokine expression and consequently cancer risk. Using logistic regression, we estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between SNPs of interleukin (IL)-1β, 6, 8, and 10 alone or combined with flavonol intake or serum IL concentration changes, and adenoma recurrence in 808 participants from the intervention arm of the Polyp Prevention Trial, a 4-year intervention study evaluating the effectiveness of a low-fat, high-fiber, high-fruit and vegetable diet on adenoma recurrence. Overall, SNPs in genes encoding IL-1β, 6, 8, and 10 were not associated with their corresponding serum concentrations or adenoma recurrence. However, individuals homozygous for IL-10 -592 C (OR=2.23, 95% CI: 1.07-4.66, P(interaction)=0.03) orIL-10 -819 C (OR=2.18, 95% CI: 1.05-4.51, P(interaction)=0.05) had an elevated risk of high-risk adenoma recurrence when their serum IL-10 concentrations increased during the trial. In addition, IL-6 -174 GG in combination with above median flavonol intake (OR=0.14, 95% CI: 0.03-0.66) or with decreased IL-6 concentrations (OR=0.14, 95% CI: 0.03-0.65) reduced the risk of advanced adenoma recurrence, although the interaction term was not statistically significant. In conclusion, our results suggest that IL SNPs, in combination with a flavonol-rich diet or decreased serum IL, may lower the risk of adenoma recurrence.

Baseline Plasma Total Homocysteine and Adenoma Recurrence: Results from a Double Blind Randomized Clinical Trial of Aspirin and Folate Supplementation

Elevated plasma total homocysteine (tHcy) is an accepted marker of functional folate deficiency but may have independent effects on colorectal neoplasia risk. It is uncertain whether plasma tHcy is associated with risk at the low levels common in a folate-fortified population. Study subjects, about half of whom were recruited after fortification of grain products with folic acid in the United States and Canada, consisted of 871 individuals with a recent history of one or more colorectal adenomas who were randomized to receive either a 1 mg/day folic acid supplement or a placebo within one of three randomly assigned aspirin treatment groups (placebo, 81, or 325 mg/day). Nonfasting plasma tHcy was determined by a gas chromatograph mass chromatography method. We estimated adjusted risk ratios and 95% confidence intervals (95% CI) for one or more adenoma recurrences for each quartile of baseline plasma tHcy using generalized linear regression with an overdispersed Poisson approximation to the binomial. The Q4/Q1 adjusted risk ratio for any adenoma was 0.98 (95% CI, 0.70-1.38; P trend = 0.17) in the placebo group, and 0.81 (95% CI, 0.58-1.12; P-trend = 0.17) in the folic acid group. Results were similar for adenomas with advanced features. There was no modification by sex, aspirin treatment group or MTHFR 677C>T genotype. Plasma tHcy is not an independent marker for an increase in colorectal adenoma recurrence risk in postfortification populations in which plasma tHcy levels are in the lower range of values. Controlling plasma tHcy levels is unlikely to favorably modify adenoma recurrence risk in folate-fortified populations.

The Association of Obesity with Short- and Long-Term Risk of Adenoma Recurrence: Analysis of the Polyp Prevention Trial and Continued Follow-Up Study: 2010 ACG Colorectal Cancer Prevention Abstract Award

The Association of Obesity with Short- and Long-Term Risk of Adenoma Recurrence: Analysis of the Polyp Prevention Trial and Continued Follow-Up Study: 2010 ACG Colorectal Cancer Prevention Abstract Award

Chemoprevention of colorectal cancer: systematic review and economic evaluation

Chemoprevention of colorectal cancer: systematic review and economic evaluation

Serum Adiponectin, Leptin, C-Peptide, Homocysteine, and Colorectal Adenoma Recurrence in the Polyp Prevention Trial

Serum adiponectin, leptin, C-peptide, and homocysteine are indicators for obesity, hyperinsulinemia, and chronic inflammation, which have all been associated with colorectal cancer. To determine whether serum adiponectin, leptin, C-peptide, and homocysteine are associated with fat, fiber, fruit and vegetable, flavonol, or dry bean intake and colorectal adenoma recurrence. Using logistic regression, we estimated odds ratios (OR) and 95% confidence intervals (95% CI) for adenoma recurrence in 627 participants from the control arm of the Polyp Prevention Trial, a 4-year trial that examined the effectiveness of a low-fat, high-fiber, high-fruit and vegetable diet on adenoma recurrence. Serum concentrations of C-peptide and homocysteine were inversely related to fiber, fruit and vegetable, and flavonol intake and positively related to percentage of calories from fat (all P(trend) < or = 0.01). High homocysteine concentrations were associated with any (4th versus 1st quartile: OR, 2.26; 95% CI, 1.30-3.94) and more than one adenoma recurrence (OR, 2.11; 95% CI, 1.01-4.40). Individuals in the highest, versus lowest, tertile of serum leptin concentration had a decreased risk of advanced adenoma recurrence (OR, 0.22; 95% CI, 0.06-0.79). Our results suggest that serum homocysteine may serve as an indicator of dietary exposure, including a low-fat and high-fiber, high-fruit and vegetable, and high-flavonol diet, as well as colorectal adenoma recurrence. Discovering biomarkers that are both modifiable and can predict cancer risk is critical. We identified serum homocysteine as a novel indicator that is modified by diet and predicts risk of adenoma recurrence.

140 Protective Effect of a Phytoestrogen-Enriched Diet on the Increase in Visceral Sensitivity and Intestinal Permeability Induced by Acute Stress in Female Rats

Background: Studies have suggested obesity as a risk factor for colorectal adenoma recurrence. It is unknown if weight change affects the risk of adenoma recurrence. Aim: We sought to examine whether weight change over a four year period is associated with subsequent colorectal adenoma recurrence. Methods: A total of 1,826 participants with a history of colorectal adenoma had body weight measured at baseline and 4 years later in the Polyp Prevention Trial. Adenoma recurrence was determined by end of trial colonoscopy. We used multinomial regression models to estimate adjusted relative risk ratios (RRR) and 95% confidence intervals (CI) to evaluate body mass index (BMI), weight change over 4 years and the risk of incident non-advanced and advanced adenoma recurrence. Results: A total of 605 (33.1%) participants had non-advanced adenoma recurrence while 118 (6.5%) had advanced adenoma recurrence. Although relative risks in this data set did not quite reach statistical significance, the analytic results suggest that baseline adiposity, especially BMI ≥ 30 kg/m2, is positively associated with adenoma recurrence. When compared with participants with BMI < 25 kg/m2 (n = 466) at baseline, there was an elevated risk of nonadvanced adenoma and advanced adenoma recurrence among participants with BMI = 25 29 kg/m2 (n = 868) (RRR = 1.23; 95%CI: 0.95-1.59 and RRR = 1.02; 95%CI: 0.61-1.68, respectively) and among those with BMI ≥ 30 kg/m2 (n = 492) (RRR = 1.27; 95%CI: 0.951.70 and RRR = 1.63; 95%CI: 0.96-2.78, respectively). When compared with those with relatively stable weight (less than 5 pound weight change) over the 4-year trial, weight gain or loss was not associated with adenoma recurrence (Table); this was consistent regardless of the baseline BMI. Conclusions: We observed a suggestive positive association between baseline BMI and adenoma recurrence; however, weight loss or gain over 4 years does not affect adenoma recurrence irrespective of baseline weight. Adjusted for age, sex, non-steroidal anti-inflammatory drug use, smoking and family history of colorectal cancer

143 Obesity, Weight Change and the Risk of Adenoma Recurrence in the Polyp Prevention Trial

143 Obesity, Weight Change and the Risk of Adenoma Recurrence in the Polyp Prevention Trial

Abstract 2831: Ornithine decarboxylase polymorphisms and risk of colorectal adenoma

Abstract Introduction: In a recent randomized trial the combination of difluoromethylornithine (DFMO) and the NSAID sulindac was remarkably effective in reducing the risk of colorectal adenoma recurrence. DFMO is a specific inhibitor of ornithine decarboxylase (ODC), which catalyzes the first step in polyamine synthesis. ODC and polyamines, which regulate cell growth and survival, have long been associated with colon carcinogenesis. In previous studies a SNP in the ODC promoter region was associated with risk of adenoma and response to aspirin treatment. The objective of this research was to perform a more comprehensive investigation of the association of adenoma risk with common genetic variation across the entire ODC gene, including potential upstream and downstream regulatory regions. Methods: We investigated the association between genetic variation in the ODC gene and risk of adenoma recurrence among a cohort of 920 participants in the Aspirin/Folate Polyp Prevention Study. Using the Sequenom platform, we genotyped 29 SNPs within a 23kb region. Generalized linear regression was used to compute relative risks (RRs) and 95% confidence intervals (95% CIs) adjusted for age and gender. Interactions terms were used to test whether ODC genotype modified the protective effect of aspirin treatment. Results: As gene frequencies for 26 of the 29 SNPs varied significantly by race/ethnicity, analyses were limited to whites only (86%). There were 7 SNPs associated with increased risk and 3 with decreased risk of adenoma recurrence (see table). In addition, at least three SNPs without any main effect modified the effect of aspirin treatment: rs1405948 (P for interaction=0.048), rs28362422 (P=0.043), and rs4669584 (P=0.050). Conclusion: Our findings suggest that common genetic variation throughout the ODC gene and adjacent regulatory regions influence risk of adenoma recurrence as well as efficacy of aspirin treatment.Association of ODC polymorphisms with adenoma riskSNPRR95% CIP-valueModelMAFLocationrs23575511.231.06-1.440.008dominant0.345′ flankingrs23026141.371.08-1.740.009dominant0.04exon 2rs37526611.351.06-1.720.017dominant0.04intron 5rs10495001.381.08-1.750.009dominant0.04exon 12rs8181620.700.52-0.940.019recessive0.303′ flankingrs109296691.251.06-1.480.009dominant0.113′ flankingrs24634630.760.62-0.930.009recessive0.443′ flankingrs24304201.251.08-1.460.004dominant0.323′ flankingrs116949111.341.13-1.590.001dominant0.113′ flankingrs130009160.770.63-0.040.009recessive0.453′ flanking Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2831.

Abstract 2889: Folic acid for the prevention of colorectal adenomas: Combined analysis of randomized clinical trials

Abstract Studies have suggested that poor folate status is associated with a higher risk of colorectal adenomas and cancer. However, some epidemiological and animal studies have provided contradictory evidence. Data from a few randomized clinical trials of folic acid supplementation for the prevention of colorectal adenomas have been reported. Two small trials reported at least suggestions of benefit, but this was not observed in two much larger trials, the Aspirin/Folate Polyp Prevention Study (AFPPS) and the United Kingdom Colorectal Adenoma Prevention (ukCAP). Findings from Nurses’ Health Study/Health Professional Follow-Up Study (NHS/HPFS) showed no overall risk reduction, but some indications of decreased risks in selected subgroups of individuals. To obtain more precise clinical evidence on the effects of folic acid on incident adenoma occurrence, we conducted a collaborative pooled analysis of the largest trials: AFPPS, NHS/HPFS and the ukCAP trials, focusing on the treatment periods of the studies. To address the possibility that there may be subgroups of individuals who may be more susceptible to the effects of folic acid in the large bowel, we conducted a stratified analysis by selected patient characteristics and dietary exposures. Participants included 2,007 men and women with a recent history of adenomas randomized to 0.5 or 1.0 mg/day of folic acid (n=1,008) or placebo (n=999) who had a follow-up colonoscopy 6 to 42 months after randomization (mean=30.6 (SD=8.1) months). We used random-effects meta-analysis to estimate risk ratios (RR's) and 95% confidence intervals (CI). The RR comparing folic acid vs. placebo for the occurrence of at least one adenoma was 0.99 (95% CI=0.84−1.16). For advanced lesions, the RR was 1.05 (95% CI=0.80-1.39). There was a non-significant increased risk among individuals with two or more baseline adenomas (RR, 1.14; 95% CI=0.98 -1.33) and no association among those with only one adenoma at baseline (RR, 0.88; 95% CI=0.73-1.06, P-interaction=0.03). Folic acid supplementation was also associated with a non-significantly increased risk of adenomas for individuals in the highest tertile of baseline plasma folate (&amp;gt;25 nmol/L) (RR, 1.19; 95% CI=0.92-1.53), and a non-significantly lower risk in those in the lowest tertile (&amp;lt;13.5 nmol/L) (RR, 0.79; 95% CI=0.43-1.43, P-interaction=0.39). Among non-drinkers, there was a non-significant increase in risk of adenoma recurrence in the folic acid groups (RR=1.33, 95% CI=0.63-2.81), in contrast to a null effect among subjects who consumed one or more drinks per day (RR= 0.95, 95% CI=0.54-1.69, p-interaction=0.74). Similar results were observed for advanced lesions. Results from this pooled analysis suggest that during the first few years of folic acid use, there is no clear decrease or increase in the occurrence of new adenomas in patients with a recent adenoma history. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2889.

Meta‐analysis: folic acid in the chemoprevention of colorectal adenomas and colorectal cancer

Folic acid has been identified as a possible agent for the chemoprevention of colorectal cancer. To assess the effectiveness of folic acid in reducing the recurrence of adenomas (precursors of colorectal cancer) among populations with a history of adenomas and the incidence of colorectal cancer within average-risk populations. Systematic review of randomized controlled trials comparing folic acid alone, or with other agents, vs. placebo. Eight databases were searched for relevant trials. Meta-analysis was performed. The literature search retrieved 3785 citations. Six studies met the inclusion criteria. Meta-analysis of three studies in individuals with a history of adenomas showed no statistically significant difference in the relative risk of adenoma recurrence (RR 0.93, P = 0.27). A sensitivity analysis of the two higher quality trials changed the direction of effect (RR 1.16, P = 0.11). Meta-analysis of three trials in general populations demonstrated no statistically significant effect on the relative risk of colorectal cancer (RR 1.13, P = 0.54). In all three analyses, outcome event rates were higher in individuals receiving folic acid. There is no evidence that folic acid is effective in the chemoprevention of colorectal adenomas or colorectal cancer for any population.

Abstract A112: Flavonol intake may modify the association between interleukin genetic polymorphisms and colorectal adenoma recurrence in the polyp prevention trial

Abstract Background: Interleukin (IL) 1β, 6, and 8 are pro-inflammatory cytokines that may promote colorectal carcinogenesis, whereas IL-10 is an anti#x2010;inflammatory cytokine with pro- and anti-carcinogenic effects. Single nucleotide polymorphisms (SNPs) in the promoter regions of these cytokine genes may alter inflammation and consequently colorectal carcinogenesis. Flavonols, found in fruits and vegetables, have anti-inflammatory and chemopreventive properties and they may modify the effect of SNPs in IL-encoding genes on colorectal carcinogenesis. Aims: To determine whether SNPs in IL-1β, 6, 8, and 10 were associated with their corresponding serum concentrations and adenoma recurrence and whether flavonol consumption modified these associations. Methods: Using logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for SNPs in IL-encoding genes, flavonol intake, and risk of adenoma recurrence in 1,687 participants of the Polyp Prevention Trial, a 4-year trial of a low-fat, high-fiber, high-fruit &amp; -vegetable, flavonol-rich diet. Results: Overall, SNPs in genes encoding IL-1s, IL-6, IL-8, IL-10 were not associated with their corresponding serum concentrations or adenoma recurrence. However, statistically significant interactions were observed between flavonol intake and IL-8 -251 T &amp;gt; A genotype for any (P = 0.04) and advanced adenoma recurrence (P = 0.01). Individuals consuming above the median level of flavonol intake and had IL-8 -251 AA (vs. TT) had an increased risk of any (OR = 1.54, 95% CI: 1.00–2.39) and advanced adenoma recurrence (OR = 4.44, 95% CI: 1.32–15.0). Conclusion: Our results suggest that flavonol consumption may modify the association between IL-8 SNPs and colorectal adenoma recurrence. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A112.

Uracil misincorporation into DNA and folic acid supplementation

Folate deficiency decreases thymidylate synthesis from deoxyuridylate, which results in an imbalance of deoxyribonucleotide that may lead to excessive uracil misincorporation (UrMis) into DNA during replication and repair. We evaluated the relation between UrMis in different tissues and the effect of folate supplementation on UrMis. We analyzed UrMis concentrations in rectal mucosa (n = 92) and white blood cells (WBCs; n = 60) among individuals randomly assigned to receive supplementation with 1 mg folate/d or placebo, who were then evaluated for colorectal adenoma recurrence. As expected, total homocysteine was significantly lower among the study participants who received active folate treatment (Wilcoxon's P = 0.003) than among those in the placebo group. The median UrMis concentration in rectal mucosa and WBCs among individuals treated with folate was not significantly lower than that in those who received placebo (Wilcoxon's P = 0.17). UrMis concentrations in both rectal mucosa and WBCs did not correlate significantly with folate measured in plasma and red blood cells. UrMis in rectal mucosa was marginally associated with an increased risk of adenoma recurrence (odds ratio per SD: 1.43; 95% CI: 0.91, 2.25). UrMis measurements in WBCs are not a robust surrogate for UrMis measurements in the rectal mucosa (Spearman correlation coefficient = 0.23, P = 0.08). Furthermore, folate supplementation in an already replete population (half treated with folic acid supplements and all exposed to folic acid fortification of the food supply) was not significantly associated with reduced UrMis in rectal mucosa cells or WBCs. Large-scale studies are needed to evaluate whether excessive UrMis concentrations are an important risk factor for colorectal neoplasia. This trial was registered at clinicaltrials.gov as NCT00272324.

The Effect of Strict Adherence to a High-Fiber, High-Fruit and -Vegetable, and Low-Fat Eating Pattern on Adenoma Recurrence

Individual differences in dietary intake are thought to account for substantial variation in cancer incidence. However, there has been a consistent lack of effect for low-fat, high-fiber dietary interventions and risk of colorectal cancer. These inconsistencies may reflect the multistage process of cancer as well as the range and timing of dietary change. Another potential reason for the lack of effect is poor dietary adherence among participants in these trials. The authors examined the effect of strict adherence to a low-fat, high-fiber, high-fruit and -vegetable intervention over 4 years among participants (n = 1,905) in the US Polyp Prevention Trial (1991-1998) on colorectal adenoma recurrence. There was a wide range of individual variation in the level of compliance among intervention participants. The most adherent participants, defined as "super compliers" (n = 210), consistently reported that they met or exceeded each of the 3 dietary goals at all 4 annual visits. Multivariate logistic regression models were used to estimate the association between dietary adherence and adenoma recurrence. The authors observed a 35% reduced odds of adenoma recurrence among super compliers compared with controls (odds ratio = 0.65, 95% confidence interval: 0.47, 0.92). Findings suggest that high compliance with a low-fat, high-fiber diet is associated with reduced risk of adenoma recurrence.

Using the Results of a Baseline and a Surveillance Colonoscopy to Predict Recurrent Adenomas With High-Risk Characteristics

Suggested intervals for postpolypectomy surveillance colonoscopy are currently based on the adenoma findings from the most recent examination. To determine the risk for clinically significant adenoma recurrence on the basis of the results of 2 previous colonoscopies. Prospective cohort study. Academic and private centers in North America. Participants in an adenoma chemoprevention trial in which all participants had 1 or more adenoma found on complete colonoscopy at entry. For this analysis, only participants whose qualifying adenoma was their first were included. All participants then underwent second and third study colonoscopies at roughly 3-year intervals. Proportion of patients with high-risk findings at the third study colonoscopy--either at least 1 advanced (> or = 1 cm or advanced histology) adenoma or multiple (> or = 3) adenomas. Fifty-eight of 564 participants (10.3%) had high-risk findings at the third study examination. If the second examination showed high-risk findings, then results from the first examination added no significant information about the probability of high-risk findings on the third examination (18.2% for high-risk findings on the first examination vs. 20.0% for low-risk findings on the first examination; P = 0.78). If the second examination showed no adenomas, then the results from the first examination added significant information about the probability of high-risk findings on the third examination (12.3% if the first examination had high-risk findings vs. 4.9% if the first examination had low-risk findings; P = 0.015). This observational study cannot specifically examine adenoma recurrence risk at intervals suggested for patients with low-risk adenomas (for example, 5 years vs. 10 years). Information from 2 previous examinations may help identify low-risk populations that benefit little from intense surveillance. Surveillance guidelines might be tailored in selected patients to use information from 2 previous examinations, not just the most recent one. National Institutes of Health.

Does the Location of Adenoma At Baseline Predict the Location of Subsequent Recurrence? Evidence from the Polyp Prevention Trial

Background: Studies have suggested possible biological differences between proximal and distal colon neoplasia. There is limited prospective data on the role of location in colorectal carcinogenesis. Aim: To examine whether the baseline location of adenoma predict the location of subsequent recurrence. Methods: The Polyp Prevention Trial was a 4-year, multicenter, randomized control trial which evaluated the effect of a low fat, high fiber, fruits and vegetable diet on the risk of colorectal adenoma recurrence. A total of 1,864 participants had complete information on the location of their baseline adenomas and completed the trial. We examined the association between baseline adenoma location on subsequent distal (rectosigmoid to splenic flexure) and proximal (transverse colon to cecum) adenoma recurrence. We used multinomial regression models to estimate the Relative Risks (RR) and 95% confidence intervals (CI). Results: A total of 1,131 (60.7%) subjects did not have adenoma recurrence while 733 (39.3%) subjects had adenoma recurrence (228 distal only; 369 proximal only; and 136 in both distal and proximal colon). Overall, given adenoma recurrence, there was a tendency towards a proximal shift (Table). In multivariable analysis with adjustment for age, sex, body mass index, family history of colorectal cancer and use of non-steroidal anti-inflammatory drugs, subjects with only proximal adenoma at baseline were less likely to have only distal adenoma recurrence (RR = 0.69; 95% CI: 0.47-1.00), but were more likely to have proximal adenoma recurrence (RR = 1.58; 95% CI: 1.20-2.09). Participants with proximal and distal adenomas at baseline were more likely to have adenoma recurrence in both locations: (RR = 1.61; 95% CI: 1.11-2.33) for distal only and (RR = 2.11; 95% CI: 1.53-2.90) for proximal only adenoma recurrence. Conclusions: Our study suggests a proximal shift of metachronous adenomas and subjects with adenomas in both distal and proximal colon are at the highest risk of adenoma recurrence.

Utilization and Yield of Surveillance Colonoscopy in the Continued Follow-Up Study of the Polyp Prevention Trial

Prospective information on the use and yield of surveillance colonoscopy is limited. We examined the use and yield of surveillance colonoscopy among participants in the Polyp Prevention Trial (PPT) after the 4-year dietary intervention trial ended. We followed a cohort of 1297 participants. We calculated the cumulative probability of posttrial colonoscopy and investigated the yield and predictive factors for adenoma and advanced adenoma recurrence over a mean time of 5.9 years. Seven-hundred seventy-four subjects (59.7%) had a repeat colonoscopy. Among 431 subjects with low-risk adenomas (1-2 nonadvanced adenomas) at baseline and no adenoma recurrence at the end of the PPT (lowest-risk category), 30.3% underwent a repeat colonoscopy within 4 years. Among 55 subjects who had high-risk adenomas (advanced adenoma and/or > or =3 nonadvanced adenomas) at baseline and again at the final PPT colonoscopy (highest-risk category), 41.3% had a colonoscopy within 3 years and 63.5% had an examination within 5 years. The cumulative yield of advanced adenoma through 6 years was 3.6% for the lowest-risk category, 38.9% for the highest-risk category, and ranged from 6.6% to 13.8% for intermediate-risk categories. An advanced adenoma at the final PPT colonoscopy was associated significantly with an advanced adenoma recurrence during surveillance (hazard ratio, 6.2; 95% confidence interval, 2.5-15.4). Surveillance colonoscopy was overused for low-risk subjects and underused for high-risk subjects. Advanced adenoma yield corresponded with the adenoma risk category. Resource consumption can be better managed by aligning use with the risk of adenoma recurrence.

Abstract A62: Magnesium, calcium, and colorectal adenoma recurrence: Results from a randomized trial

Abstract A62 Background Mean magnesium intake in the US population is similar to that in East Asian populations with traditionally low risks of colorectal cancer and other chronic diseases, while the ratio of calcium to magnesium is much higher in the US population. It was recently reported that intakes of calcium or magnesium were associated with a reduced risk of adenoma or hyperplastic polyps only when dietary ratios of calcium to magnesium intake was low. Objective To test whether calcium supplementation reduces the risk of colorectal adenoma recurrence only when calcium/magnesium intake ratio is low. Design: The Calcium Polyp Prevention Study was a double-blind, placebo-controlled, randomized trial of 4 years of calcium supplementation (1000 mg) for the prevention of colorectal adenoma recurrence among 930 subjects. Participants underwent two follow-up colonoscopies, 1 year and 4 years after the qualifying exam. A validated semi-quantitative food frequency questionnaire was given at study entry and year 4 to obtain subjects’ usual diet over the previous year. The primary outcome in this analysis was the recurrence of adenomas during the main risk period (i.e. adenomas detected after the year 1 colonoscopy through the year 4 exam). This end point allowed for a latent period of calcium effect and minimized the number of adenomas overlooked at the qualifying colonoscopy. Results We found that dietary ratios of calcium to magnesium intake modified the effect of calcium treatment on adenoma recurrence (p for interaction: 0.075 for all adenoma and 0.046 for tubular adenoma during the main risk period). Calcium supplementation reduced the risk of adenoma recurrence only if the dietary ratio of calcium to magnesium intake was low before treatment and remained low during the treatment period. The RR (95%CI) was 0.68 (0.52-0.90) among those with the baseline ratio below the median in comparison to 0.98 (95%CI=0.75-1.28) for those above. Findings were similar when the intake ratio at year 4 was considered and when we repeated the analyses using adenomas detected during the full study period (e.g. including adenomas identified at year 1) and found very similar results. The sample size, however, became small when advanced adenomas were used as outcome; none of the associations were significant in the stratified analyses by calcium: magnesium ratio and the calcium effect did not differ substantially by ratio stratum (p for interaction, 0.575). We also found that high dietary intake of magnesium was related to a reduced risk of adenoma recurrence among subjects in the calcium treatment arm with a low ratio of calcium to magnesium intake; the RRs (95%CIs) for any adenoma were 0.66 (0.39-1.13) and 0.58 (0.32-1.06) for the intermediate and the highest intake tertiles vs. the lowest intake tertile of magnesium (p for trend, 0.054). There was no association observed in the placebo arm. Conclusions: We found that calcium supplementation reduced the risk of adenomas only among subjects with a low calcium:magnesium intake ratio. These findings, if confirmed, may provide a new avenue for the personalized prevention of colorectal cancer. The abstract is on behalf of the Polyp Prevention Study Group. Citation Information: Cancer Prev Res 2008;1(7 Suppl):A62.

Dopamine D2receptor polymorphisms and adenoma recurrence in the Polyp Prevention Trial

Epidemiological evidence suggests that obesity may be causally associated with colorectal cancer. Dopamine and the dopaminergic reward pathway have been implicated in drug and alcohol addiction as well as obesity. Polymorphisms within the D2 dopamine receptor gene (DRD2) have been shown to be associated with colorectal cancer risk. We investigated the association between DRD2 genotype at these loci and the risk of colorectal adenoma recurrence in the Polyp Prevention Trial. Odds ratios (OR) and 95% confidence intervals (CI) for risk of adenoma recurrence were calculated using unconditional logistic regression. Individuals with any, multiple (>or=2) or advanced adenoma recurrence after 4 years were compared to those without adenoma recurrence. Variation in intake of certain dietary components according to DRD2 genotype at 3 loci (rs1799732; rs6277; rs1800497) was also investigated. The DRD2 rs1799732 CT genotype was significantly associated with all adenoma recurrence (OR: 1.30; 95% CI: 1.01, 1.69). The rs1800497 TT genotype was also associated with a significantly increased risk of advanced adenoma recurrence (OR: 2.40; 95% CI: 1.11, 5.20). The rs1799732 CT and rs1800497 TT genotypes were significantly associated with adenoma recurrence in the Polyp Prevention Trial. Increased risk of adenoma recurrence as conferred by DRD2 genotypes may be related to difference in alcohol and fat intake across genotypes.

Polyp Surveillance

Surveillance after colonic polypectomy is important to detect and remove missed synchronous polyps and cancers and new metachronous polyps or cancers. The authors review methods of surveillance and the risk of recurrent adenomas and provide surveillance recommendations.

Hyperplastic Polyps and the Risk of Adenoma Recurrence in the Polyp Prevention Trial

Recent studies have suggested that some hyperplastic polyps may be associated with an increased risk of colorectal cancer. Prospective information on the risk of adenoma recurrence associated with hyperplastic polyps is limited. We sought to investigate whether the coexistence of hyperplastic polyps with adenomas increases the risk of adenoma recurrence. We used unconditional logistic regression models to examine the association between baseline hyperplastic polyps and subsequent adenoma recurrence during a 3-year follow-up evaluation, among 1637 participants in the Polyp Prevention Trial. A total of 437 participants (26.7%) had hyperplastic polyps coexisting with adenomas at baseline. Of these, 132 (30.2%) had at least one hyperplastic polyp in the proximal colon, whereas 305 (69.8%) had only distal hyperplastic polyps. When compared with subjects without any hyperplastic polyps at baseline, there was no statistically significant association between the presence of baseline hyperplastic polyps and recurrence of any adenoma (odds ratio [OR], 1.19; 95% confidence interval [CI], 0.94-1.51) or advanced adenoma (OR, 1.25; 95% CI, 0.78-2.03). Also, there was no association between hyperplastic polyp location and adenoma recurrence (OR, 1.01; 95% CI, 0.69-1.48) for any proximal hyperplastic polyp (OR, 1.26; 95% CI, 0.96-1.65) and for distal hyperplastic polyps. The coexistence of hyperplastic polyps with adenomas, irrespective of location, does not confer an increased risk of adenoma recurrence beyond that of adenomas alone within 3 years of follow-up evaluation. Prospective long-term studies on adenoma recurrence risk associated with hyperplastic polyps in screening populations are needed.