Risk Of Advanced Adenomas Research Articles

Association of small versus diminutive adenomas and the risk for metachronous advanced adenomas: data from the New Hampshire Colonoscopy Registry

Limited data are available to investigate the impact of index adenoma size on the risk of metachronous advanced adenomas. Our goal was to examine the impact of having small (5-9mm) versus diminutive (<5mm) adenomas on the future risk of advanced adenomas within the categories for polyps<1 cm currently used in the United States: 1 to 2 and 3 or more tubular adenomas. We included data from individuals participating in the statewide, population-based New Hampshire Colonoscopy Registry (NHCR). Groups were based on index findings: (1) 1 to 2 adenomas<5mm (both diminutive), (2) 1 to 2 adenomas<1 cm (one or both small), (3) 3 to 10 adenomas<5mm (all diminutive), (4) 3 to 10 adenomas<1 cm (one or more small), and (5) advanced adenomas (AA). AAs were defined as adenomas≥1cm or those with villous elements or high-grade dysplasia or colorectal cancer (CRC). Outcomes were the absolute and adjusted risk of metachronous AAs. Covariates included age, sex, body mass index, family history of CRC, lifestyle factors, presence of serrated polyps, and time since the index examination. After adjusting for the covariates, we observed that having 1 to 2 adenomas with at least one 5 to 9mm adenoma (adjusted odds ratio [AOR], 1.54; 95% confidence interval [CI], 1.12-2.11), 3 to 10 diminutive adenomas (AOR, 1.75; 95% CI, 1.03-2.95), 3 to 10 adenomas<1 cm (1 or more small) (AOR, 2.14; 95% CI, 1.39-3.29) or AAs (AOR, 2.77; 95% CI, 2.05-3.74) were associated with an increased risk for metachronous AA compared with having 1 to 2 diminutive adenomas. A further stratification of group 2 showed that those with exactly 2 small adenomas had an absolute risk of future AA of 7.6% (11/144) (95% CI, 4.3%-13.2%), higher than the absolute risk in the 1 to 2 diminutive polyp group, and similar to the risk for 3 to 10 adenomas of 8.2% (95% CI, 5.4-11.9). For individuals with 1 to 2 adenomas<1 cm, having at least 1 small adenoma increased the metachronous risk of AA compared with having only diminutive adenomas. Furthermore, the subset with 2 small adenomas had a risk of future AA similar to the risk for 3 to 10 adenomas. These data suggest that individuals with at least 1 small adenoma may be at higher risk for future AAs and thus require closer follow-up than those with only diminutive adenomas. These data may be valuable to guideline committees for the creation of future surveillance recommendations.

Fecal Hemoglobin Concentration, a Good Predictor of Risk of Advanced Colorectal Neoplasia in Symptomatic and Asymptomatic Patients.

Background: Periodical fecal immunochemical testing (FIT) is a cost-effective strategy in colon cancer screening programmes. FIT is also used as a diagnostic test in symptomatic patients, but data, are scarce.Aim: To determine the association between FIT-Hb concentration and the risk of advanced neoplasia (AN) detected in colonoscopy in two different populations.Methods: The outcomes of colonoscopies performed after a positive FIT (>117 ng/ml) (Sentinel Gold test) result were analyzed in patients included within a population-based CRC screening programme (screening group) and, as diagnostic evaluation in symptomatic patients (symptomatic group). The study was performed between January 1st, 2014 and October 31, 2016. Data are reported as medians with interquartile ranges or frequencies and percentages. Positive predictive value (PPV) at arbitrary fecal hemoglobin concentrations were also reported calculated for AN.Results: We recruited 2742 patients who underwent a colonoscopy procedure, 1515 (53.5%) of them within the CRC screening programme. Patients in the screening group were younger (65.0 ± 3.3 vs. 66.2 ± 13.4 years, p < 0.001) and more frequently male (p < 0.001) vs. the symptomatic group. Colonoscopy found more frequently neoplastic lesions in the screening compared to the symptomatic group (61.9 vs. 44.8% p < 0.001). Hb concentration in FIT was significantly higher in patients with AN compared with patients without AN in both groups (p < 0.001). The age-adjusted risk of AN increased significantly in both groups according to FIT Hb concentration in the Quartile 3 [OR (95% CI): 2.94 (2.33–3.71)] and Quartile 4 [OR: 5.52 (4.36–6.99)]. Males, in both groups showed a higher probability of presenting AN. FIT values were higher for left- than for right-sided AN in the screening, but not in the symptomatic group. Positive predictive values for AN were higher in the screening group in positive FIT tests (range 43.9–70.5%; 117 to >1,000 ng/ml) compared to those in the symptomatic group (36.3–52.5%). Similar trends were observed for cancer diagnosis alone.Conclusions: Male gender, age, and FIT Hb concentration are predictors of risk of advanced adenoma and colorectal cancer and can be used to prioritize colonoscopy in patients with suspected advanced neoplasia, both in screening and in symptomatic patients.

Prevalence and characteristics of colonic adenoma in mainland China.

Background and aimTo investigate the prevalence and characteristics of colonic adenoma and advanced colonic adenoma in a large group of patients in mainland China.Materials and methodsWe conducted a cross-sectional study on patients who had undergone colonoscopy examination in a university hospital in mainland China. Colonic adenomas and advanced adenomas were recorded.ResultsThe prevalence of polyps, adenoma, and advanced adenoma was 23.9%, 13.3%, and 3.5%, respectively. Age and sex were independent risk factors for the prevalence of adenoma and advanced adenoma. Polyp size was associated with an increased risk of both colonic adenoma (OR 1.50, 95% CI 1.44–1.56) and advanced adenoma (OR 2.78, 95% CI 2.55–3.03) after sex and age adjustment. Proximal colon polyps were a risk factor for adenoma (OR 1.41, 95% CI 1.20–1.66) and also associated with a significant reduction (44%) in risk of advanced adenoma (OR 0.56, 95% CI 0.36–0.86) compared to distal colon adenoma after sex and age adjustment. A screening indication was associated with a statistically significant decrease in the odds of prevalence of adenoma (OR 0.90, 95% CI 0.81–0.99) and advanced adenoma (OR 0.72, 95% CI 0.59–0.88) compared to a no-screening indication.ConclusionThe overall prevalence of adenoma was low in mainland China. It exhibited a varied pattern with respect to age and sex. Polyp size was a risk factor for both colonic adenoma and its transition to advanced adenoma. Proximal colon polyps were a risk factor for adenoma, but a protective factor for advanced adenoma compared to distal colon adenoma.

Dairy intake during high school and risk of colorectal adenomas in women

Introduction There is substantial evidence including from meta-analyses that higher dairy intake during adulthood is associated with lower risk of colorectal cancer. In contrast, little is known about the association between adolescent dairy intake and risk of colorectal neoplasia. Only two studies have previously investigated the association between dairy intake in early life and later risk of colorectal neoplasia, with conflicting results, but none used a validated dietary assessment tool to define exposure. Therefore, with our study we aimed to investigate the association between dairy intake during adolescence and the risk of colorectal adenomas later in life using data from the large, prospective female cohort Nurses’ Health Study II (NHSII) in which adolescent diet was inquired retrospectively by a validated food frequency questionnaire, and participants were followed prospectively for incidence of colorectal adenomas. Methods The study population consisted of 42,975 women aged between 34 and 51 years who had reported their adolescent diet in a validated food frequency questionnaire about diet during high school (HS-FFQ) in 1998 and had undergone at least one lower bowel endoscopy during the study period, i.e. between the return of the HS-FFQ and May 31st 2011. To investigate the association between adolescent dairy intake and risk of later colorectal adenoma, we used a period-based analysis approach taking into account that NHSII participants may have undergone multiple lower bowel endoscopies during the follow-up period. We used multivariable-adjusted logistic regressions for clustered data (each participant poses a cluster) to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CI). Models were adjusted for potentially confounding factors and dairy intake during adulthood. Results Between 1998 and 2011, 2456 women were diagnosed with at least one adenoma. High dairy consumption during high school was not significantly associated with risk of colorectal adenomas (OR highest versus lowest quintile 0.89, 95% CI 0.76, 1.04). Adolescent dairy consumption was not associated with risk of proximal (OR 1.01, 95% CI 0.81,1.27) adenomas, but a statistically significant inverse association was observed for distal (including rectal) adenomas (OR 0.81, 95% CI 0.66,1.00; P-trend 0.04). Furthermore, the risk of advanced adenomas (large or villous adenomas) was lower for women with high versus low adolescent dairy intake (OR 0.70, 95% CI 0.50, 0.96; P-trend = 0.03). No association between adolescent dairy consumption and risk of non-advanced adenomas was observed (OR 0.97, 95% CI 0.79, 1.20). ORs for distal and advanced adenomas were no longer statistically significant after additional adjustment for dairy calcium intake during high school. When analyzed separately by individual dairy foods, milk, yoghurt or cheese intakes during high school were not significantly associated with risk of colorectal adenoma. Conclusions The findings suggest that dairy intake during adolescence may play a role for later risk of colorectal adenoma, independent of adult dairy intake.

Is Timing Important? The Role of Diet and Lifestyle during Early Life on Colorectal Neoplasia.

To summarize the current evidence on the most important dietary and lifestyle factors in colorectal carcinogenesis during different stages of a lifetime with special emphasis on studies investigating exposure during childhood, adolescence and young adulthood. A number of studies showed that independent of adult obesity, higher body fatness during childhood, adolescence and young adulthood is associated with risk of colorectal cancer later in life. In one large cohort study, the Nurses' Health Study II, adherence to a western pattern diet during adolescence was associated with higher risk of advanced adenoma. The current evidence relating consumption of individual foods and nutrients as well as physical activity during early life to colorectal cancer is sparse and less consistent, at least in part due to limitations in study design, such as sample size, limited data on potential confounders or lack of a validated dietary assessment instrument. As colorectal carcinogenesis is a long process and can take up to several decades to develop, early life risk factors may also be etiologically relevant. The recent rise in early-onset colorectal cancer incidence and mortality in the US, i.e., in individuals younger than 55 years at diagnosis, strongly supports that early life risk factors may influence colorectal carcinogenesis. Considering that the majority of colorectal cancers are preventable, there is an urgent need for well-designed investigations on the role of diet and lifestyle factors throughout the life course and risk of colorectal cancers.

Risk of Advanced Adenoma, Colorectal Cancer, and Colorectal Cancer Mortality in People With Low-Risk Adenomas at Baseline Colonoscopy: A Systematic Review and Meta-Analysis.

We conducted a systematic review and meta-analysis of the risk of advanced adenomas (AAs), colorectal cancer (CRC), and/or CRC-related death among individuals with low-risk adenomas (LRAs). We searched PubMed and Embase for studies published between January 2006 and July 2015. Quality and strength of the evidence were rated using the Newcastle-Ottawa Scale (NOS) and the GRADE framework, respectively. Eleven observational studies (n=64,317) were included. A meta-analysis of eight cohort studies (n=10,139, 3 to 10 years' follow-up) showed a small but statistically significant increase in the incidence of AAs in individuals with LRAs compared with those with a normal baseline colonoscopy (RR 1.55 (95% CI 1.24-1.94); P=0.0001; I2=0%). The pooled 5-year cumulative incidence of AA was 3.28% (95% CI: 1.85-5.10%), 4.9% (95% CI: 3.18-6.97%), and 17.13% (95% CI: 11.97-23.0%) for the no adenoma, LRA, and AA baseline groups, respectively. Two studies, which could not be pooled, showed a reduction in the risk of CRC in individuals with LRAs compared with the general population (standardized incidence ratio 0.68 (95% CI 0.44-0.99) at a median follow-up of 7.7 years and OR 0.4 (95% CI 0.2-0.6) at 3-5 years). One large retrospective cohort study found a 25% reduction in CRC mortality in individuals with LRAs compared with the general population (SMR 0.75 (95% CI 0.63-0.88) at a median follow-up of 7.7 years). We observed a small but significant increase in the risk of AAs in people with LRAs compared with those with a normal baseline colonoscopy, but compared with the general population, people with LRAs have significantly lower risks of CRC and of CRC-related mortality.

Surveillance after positive colonoscopy based on adenoma characteristics

BackgroundPatients with adenomatous polyps are at increased risk for developing colorectal cancer based on the characteristics and number of polyps, but less is known about the individual and combined contribution of these factors. This study aimed to better characterize the risk of advanced adenoma and cancer in patients with positive baseline colonoscopy. MethodsPatients who had polyps at baseline colonoscopy were included in this retrospective cohort study (N=1165) and were categorized into 6 groups: (1) 1–2 non-advanced adenomas (NAA’s), (2) ≥3 NAA’s, (3) advanced tubular adenoma, (4) small tubulovillous adenoma (TVA), (5) large TVA and (6) multiple advanced adenomas (MAA’s). Findings at surveillance colonoscopy were documented in each group. ResultsThe combined incidence of advanced adenoma, ≥3 NAA’s, and colorectal cancer at surveillance colonoscopy was significantly higher in the baseline large TVA (29.2%) than small TVA groups (13.5%, P<0.001), as well as in the MAA’s group (44.1%) compared with large TVA group (P=0.02). The incidence of colorectal cancer, however, was not significantly different between the groups. ConclusionsThe size of the polyp and the number of advanced lesions are more important than its histology for predicting the risk of high-risk metachronous lesions at follow-up.

Meat and fish consumption and risk of colorectal adenomas in Korea.

559 Background: Consumption of red meat and alcohol are known risk factors for colorectal cancer. Colorectal adenomas are considered precursors to colorectal cancer through adenoma-carcinoma sequence. The identification of modifiable risk factors for colorectal adenoma contributes to prevent colorectal cancer from progressing. Many studies have suggested that high red meat or processed meat intake is associated with an increased risk of colorectal adenoma. However, the effect of high fish intake on colorectal adenoma has been insufficient in epidemiological studies. The aim of this study is examine the relationship between meat and fish intake and the risk of colorectal adenoma. Methods: The study enrolled participants who visited Seoul National University Hospital Healthcare System Gangnam Center from May to December, 2011. All participants underwent screening colonoscopy and completed validated food frequency questionnaire. The study sample included 414 adenoma patients, 142 advanced adenoma patients and 1160 polyp-free controls. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between meat and fish and colorectal adenoma using multivariate logistic regression. Results: The intake of total meat, red meat, poultry or processed meat showed no clear association with risk of colorectal adenoma or advanced adenoma. A significant negative association between fish intake and risk of advanced adenoma (OR = 0.51, 95% CI = 0.27 – 0.95, p for trend = 0.0281) after adjusting for confounders such as age, BMI, family history of colorectal cancer, alcohol consumption, smoking status, diabetes, total energy intake, fiber, vegetable/fruit and red meat intake. Conclusions: In conclusion, this study showed no clear relationship between the incidence of colorectal adenoma/advanced adenoma and meat intake. Although, high fish intake and incidence of advanced adenoma showed a significant inverse association in Korean.

Metformin therapy and the risk of colorectal adenoma in patients with type 2 diabetes: A meta-analysis.

BackgroundExisting data evaluating the impact of metformin on the colorectal adenoma (CRA) risk in patients suffering from type 2 diabetes (T2D) are limited and controversial. We therefore summarized the studies currently available and assessed the relationship between metformin treatment and risk of CRA in T2D patients.MethodsWe systematically searched databases for eligible studies that explored the impact of metformin treatment on the occurrence of CRA in T2D patients from inception to June 2016. The summary odds ratio (OR) estimates with their 95% confidence interval (CI) were derived using random-effect, generic inverse variance methods. Sensitivity analysis and subgroup analysis were performed.ResultsSeven studies involving 7178 participants met the inclusion criteria. The pooling showed that metformin therapy has a 27% decrease in the CRA risk (OR, 0.73; 95% CI, 0.58 - 0.90). In subgroup analysis, we detected that metformin exhibits significant chemoprevention effects in Asia region (OR, 0.68; 95% CI, 0.48 - 0.96). Similar results were identified in both studies with adjusted ORs and high-quality studies (OR, 0.66; 95% CI, 0.50 - 0.86 and OR, 0.70; 95% CI, 0.58 - 0.84, respectively). Of note, an inverse relationship was noted that metformin therapy may result in a significant decrease in the advanced adenoma risk (OR, 0.52; 95% CI, 0.38 - 0.72). Low heterogeneity was observed, however, the results remained robust in multiplesensitivity analyses.ConclusionsThis meta-analysis indicates that metformin therapy is correlated with a significant decrease in the risk of CRA and advanced adenoma in T2D patients. Further confirmatory studies are warranted.

Statin use and the risk of colorectal adenoma: A meta-analysis.

Although statin use has been reported to reduce the risk of colorectal cancer beyond its cholesterol-lowering effects, the benefit of statins against colorectal adenoma has not been fully clarified. We aimed to investigate the association between statin use and the risk of colorectal adenoma. We conducted a systematic literature search on MEDLINE, EMBASE, and the Cochrane Library using the primary keywords "adenoma," "polyp," "colorectal," "colon," "rectal," "rectum," "neoplasia," "neoplasm," "statin," "3-hydroxy-3-methylglutaryl-coenzyme A," and "HMG-CoA." Studies were included if they evaluated the association between statin use and adenoma and reported relative risks (RRs) or odds ratios or provided data for estimation. Pooled estimates were calculated using the random-effects model. Six studies including 13 239 patients were analyzed. The median proportion of patients with any adenoma was 29.7% (range, 20.9-38.4%) in patients taking statins and 31.2% (range, 19.6-63.4%) in patients not taking statins across included studies. The median proportion of patients with advanced adenoma in those taking statins was 7.7% (range, 3.1-27.2%), whereas that in patients not taking statins was 11.3% (range, 3.5-32.4%). On meta-analysis, statin use did not significantly affect the risk of any adenoma (pooled RR = 0.901; 95% confidence interval [CI], 0.735-1.104); however, it was associated with a lower risk of advanced adenoma (pooled RR = 0.833; 95% CI, 0.750-0.925). Statin use seems to be associated with a reduced risk of advanced adenoma, but not any adenoma. Statins may prevent neoplastic progression of adenomas rather than the development of adenomas.

The association between location, age and advanced colorectal adenoma characteristics: a propensity-matched analysis

Purpose: Evidence supports an association between certain colorectal adenoma characteristics and predisposition to cancer. The association between anatomical location of colorectal adenoma, age and advanced adenomas needs attention. The objective of this study was to evaluate the possible association between occurrence of sporadic advanced adenomas with location and age.Materials and methods: A cross-sectional study using baseline data from index colonoscopy from a randomized controlled trial evaluating chemopreventive treatment against recurrence of colorectal adenomas was performed. Inclusion criteria for patients were one adenoma of >1 cm in diameter or multiple adenomas of any size, or an adenoma of any size and familial disposition for colorectal cancer. Multivariate regression and propensity score-matched analyses were used to correlate location of adenomas and age with advanced adenoma features.Results: In this study, 2149 adenomas were removed in 1215 patients. Advanced colorectal adenomas primarily occurred in the anal part of the colon. Older age was associated with more adenomas and more oral occurrence of adenomas, as well as a higher risk of advanced adenomas. Surprisingly, specifically for the oral adenomas the risk of advanced adenoma seems to be lower for older patients compared with younger.Conclusions: This study presents new results with regard to association between age, location of adenomas and risk of advanced adenomas. The results indicate that sigmoidoscopy for screening purposes may be obsolete, and add to the existing literature on which future guidelines for screening may be based.

Genetic Variants Associated with Colorectal Adenoma Susceptibility.

BackgroundCommon low-penetrance genetic variants have been consistently associated with colorectal cancer risk.AimTo determine if these genetic variants are associated also with adenoma susceptibility and may improve selection of patients with increased risk for advanced adenomas and/or multiplicity (≥ 3 adenomas).MethodsWe selected 1,326 patients with increased risk for advanced adenomas and/or multiplicity and 1,252 controls with normal colonoscopy from population-based colorectal cancer screening programs. We conducted a case-control association study analyzing 30 colorectal cancer susceptibility variants in order to investigate the contribution of these variants to the development of subsequent advanced neoplasia and/or multiplicity.ResultsWe found that 14 of the analyzed genetic variants showed a statistically significant association with advanced adenomas and/or multiplicity: the probability of developing these lesions increased with the number of risk alleles reaching a 2.3-fold risk increment in individuals with ≥ 17 risk alleles.ConclusionsNearly half of the genetic variants associated with colorectal cancer risk are also related to advanced adenoma and/or multiplicity predisposition. Assessing the number of risk alleles in individuals within colorectal cancer screening programs may help to identify better a subgroup with increased risk for advanced neoplasia and/or multiplicity in the general population.

252 Risk of Advanced Adenoma, Colorectal Cancer, and Colorectal Cancer Mortality in Individuals With Low Risk Adenomas on Baseline Colonoscopy: A Systematic Review and Meta-Analysis

252 Risk of Advanced Adenoma, Colorectal Cancer, and Colorectal Cancer Mortality in Individuals With Low Risk Adenomas on Baseline Colonoscopy: A Systematic Review and Meta-Analysis

Exam 2: Risk of Advanced Adenomas in Siblings of Individuals With Advanced Adenomas: A Cross-Sectional Study

Exam 2: Risk of Advanced Adenomas in Siblings of Individuals With Advanced Adenomas: A Cross-Sectional Study

Plasma Inflammatory Markers and Risk of Advanced Colorectal Adenoma in Women

Evidence remains inconclusive about the association of systemic inflammatory markers with colorectal neoplasia. We investigated whether circulating inflammatory markers were associated with risk of advanced colorectal adenoma. We measured plasma macrophage inhibitory cytokine-1 (MIC-1), C-reactive protein (CRP), interleukin-6 (IL6), and soluble TNF receptor 2 (sTNFR-2) in blood samples drawn from 32,826 women in 1989 to 1990 in the Nurses' Health Study. Through 2008, we documented 757 cases of advanced colorectal adenomas (≥1 cm or any size with advanced histology); each case was matched by age and time of blood draw with one control randomly selected from participants who underwent lower endoscopy and did not have neoplasia. Plasma MIC-1 was associated with higher risk of advanced adenoma (Ptrend = 0.04), with an OR of 1.55 (95% confidence interval, 1.03-2.32) comparing extreme quintiles of MIC-1 after adjusting for colorectal cancer-risk factors and other inflammatory markers. Among cases, MIC-1 level was positively associated with the number of adenomas (P < 0.001) and gradually increased from adenomas located in the rectum, distal colon, and up to the proximal colon. There was a strong positive association between MIC-1 and risk of adenomas with multiplicity, ≥1 cm size and location in the proximal colon (all Ptrend < 0.05). CRP, IL6, or sTNFR-2 was not associated with adenoma risk. In conclusion, plasma MIC-1 was associated with higher risk of colorectal adenoma, especially multiple, large, and proximal adenomas. Our results provide further support for a role for MIC-1 in carcinogenesis and the potential for MIC-1 as an adjunctive biomarker for detection of advanced colorectal adenoma.

Risk of Advanced Adenomas in Siblings of Individuals With Advanced Adenomas: A Cross-Sectional Study

The risk of colorectal neoplasms among siblings of patients with advanced adenomas is not clear. We determined the prevalence of advanced adenomas in the siblings of patients with advanced adenomas and compared it with that of siblings of individuals without these lesions. In a blinded, cross-sectional study, colonoscopies were performed (from 2010 through 2014), at 2 hospitals in Hong Kong on 200 asymptomatic siblings of patients with advanced adenomas (exposed; mean age, 58.2 ± 6.3 years; adenomas ≥10 mm, high-grade dysplasia, villous, or tubulovillous) and 400 age- and sex-matched siblings of subjects with normal findings from colonoscopies and no family history of colorectal cancer (unexposed; mean age, 58.1 ± 6 years). We recruited 1 sibling per family. The primary outcome was prevalence of advanced adenomas. Baseline demographics (ie, aspirin use, smoking, body mass index, and metabolic diseases) did not differ significantly between exposed and unexposed individuals. The prevalence of advanced adenoma was 11.5% among the exposed subjects and 2.5% among the unexposed subjects (matched odds ratio [mOR] = 6.05; 95% confidence interval [CI]: 2.74-13.36; P < .001). The prevalence of adenomas ≥10 mm was higher among exposed than unexposed siblings (10.5% vs 1.8%; mOR = 8.59; 95% CI: 3.44-21.45; P < .001), as was the prevalence of villous adenomas (5.5% vs 1.3% in unexposed; mOR = 6.28; 95% CI: 2.02-19.53; P = .001) and all colorectal adenomas (39.0% vs 19.0% in unexposed; mOR = 3.29; 95% CI: 2.16-5.03; P < .001). Two cancers were detected in exposed siblings and none in unexposed siblings. In a cross-sectional study of subjects undergoing colonoscopy in Hong Kong, siblings of individuals with at least 1 advanced adenoma had a 6-fold increased odds of advanced adenoma compared with subjects who had a sibling with a screening colonoscopy with no identified neoplasia. ClinicalTrials.gov, Number: NCT01593098.

Evaluation of pro-inflammatory markers plasma C-reactive protein and urinary prostaglandin-E2 metabolite in colorectal adenoma risk.

C-reactive protein (CRP) is a pro-inflammatory protein with potential as a biomarker in predicting colon cancer risk. However, little is known regarding its association with risk of colorectal adenomas, particularly by subtypes. We conducted a colonoscopy-based matched case-control study to assess whether elevated plasma CRP levels may be associated with colorectal adenoma risk and further whether this association may be modified by urinary prostaglandin E2 metabolite (PGE-M), a biomarker of systemic prostaglandin E2 production. Included in the study were 226 cases with a single small tubular adenoma, 198 cases with multiple small tubular adenomas, 283 cases with at least one advanced adenoma, and 395 polyp-free controls. No apparent association between CRP level and risk of single small tubular adenomas was found (ptrend = 0.59). A dose-response relationship with CRP level was observed for risk of either multiple small tubular adenomas (OR = 2.01, 95%CI = 1.10-3.68 for the highest versus lowest tertile comparison; ptrend = 0.03) or advanced adenomas (OR = 1.81, 95%CI = 1.10-2.96 for the highest versus lowest tertile comparison; ptrend = 0.02). In a joint analysis of CRP level and PGE-M, risk of multiple or advanced adenoma was greatest among those with highest levels of both CRP and PGE-M in comparison to those with low CRP and low PGE-M (OR = 3.72, 95%CI = 1.49-9.72). Our results suggest that elevated CRP, particularly in the context of concurrent elevated PGE-M, may be a biomarker of multiple or advanced adenoma risk in a screening age population. © 2015 Wiley Periodicals, Inc.

Abstract 4584: VDR genotype modifies vitamin D efficacy for colorectal adenoma prevention in a randomized controlled trial

Abstract Objective: Although epidemiological and pre-clinical research suggests that vitamin D and calcium supplementation reduce colorectal carcinogenesis, we found that they had no effect on risk of colorectal adenoma recurrence in a recently completed randomized controlled trial (Vitamin D/Calcium Polyp Prevention Study, NCT00153816). We now examine whether the effect of supplementation may be modified by common genetic variants in vitamin D and calcium pathway genes previously associated with 25-hydroxyvitamin D levels or other health outcomes. Methods: 41 candidate single nucleotide polymorphisms (SNPs) in 7 genes (GC, DHCR7, CYP2R1, CYP27B1, CYP24A1, VDR and CASR) were genotyped in non-Hispanic white trial participants (N = 1,676). All had at least one adenoma at a baseline colonoscopy and were randomized to treatment with vitamin D3 (1000 IU/day), calcium (1200 mg/day), both or placebo in a modified 2×2 factorial design. Participants were followed until a subsequent colonoscopy 3 or 5 years later and assessed for the presence of at least one adenoma or advanced adenoma (adenoma ≥1 cm, or with &amp;gt;25% villous histology and/or high-grade dysplasia, or cancer). Adjusted risk ratios (RRs) and 95% confidence intervals (CIs) were used to estimate genotype effects, treatment effects and interactions. To account for multiple testing, based on the effective number of independent SNPs, statistical significance was defined as p&amp;lt;0.002. Results: VDR SNP rs731236 (Taq1, minor allele frequency 0.39) statistically significantly modified the effect of vitamin D3 treatment on advanced adenomas (interaction RR = 0.49, 95% CI = 0.31-0.76, P = 0.001) but not on any adenoma (interaction RR = 0.94, 95% CI = 0.80-1.11, P = 0.48). Among participants (N = 249, 15%) with the homozygous variant genotype, the risk of an advanced adenoma was 15.2% among those randomized to placebo, and 3.2% among those randomized to vitamin D; a risk reduction of 78% for vitamin D supplementation (RR = 0.22, 95% CI = 0.08-0.63, P = 0.005). In contrast, among participants with one or more wild type allele (N = 1400, 85%), the risk of an advanced adenoma was 8.8% among those randomized to placebo, and 10.5% among those randomized to vitamin D; an apparent risk increase of 19% for vitamin D supplementation (RR = 1.19, 95% CI = 0.86-1.64, P = 0.3). Several other VDR SNPs in linkage disequilibrium with rs731236 had borderline statistically significant interactions. However, there were only nominally statistically significant (P&amp;lt;0.05) interactions of SNP genotypes with calcium treatment on adenoma outcomes. Conclusions: Our results suggest that the effect of vitamin D3 supplementation on colorectal carcinogenesis depends on common genetic variants in VDR, with a 78% reduction in risk of advanced adenomas in individuals with the rs731236 homozygous variant genotype, and no benefit in individuals with one or more wild type alleles. Note: This abstract was not presented at the meeting. Citation Format: Elizabeth L. Barry, Leila A. Mott, Judith R. Rees, Dennis J. Ahnen, Roberd M. Bostick, Robert S. Bresalier, Douglas J. Robertson, Robert W. Summers, John A. Baron. VDR genotype modifies vitamin D efficacy for colorectal adenoma prevention in a 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 4584. doi:10.1158/1538-7445.AM2015-4584

Su1674 Incidence of Colonic Neoplasia in Patients With Breast Cancer: Updated Systematic Review and Meta-Analysis

Su1674 Incidence of Colonic Neoplasia in Patients With Breast Cancer: Updated Systematic Review and Meta-Analysis Jennifer H. Lai, Gavin Park, Lauren B. Gerson* Gastroenterology, California Pacific Medical Center, San Francisco, CA; Internal Medicine, California Pacific Medical Center, San Francisco, CA Background: Patients with breast cancer are advised to undergo screening for colon cancer every 5 years due to a perceived increase in cancer risk. Methods: We searched Pubmed (1970-2014) and Cochrane Central Registry of Clinical Trials and included the following search terms: “colorectal neoplasms,” “genes, BRACA1”, “genes BRCA2,” “breast neoplasms,” as well as title words “breast and colorectal” with text word “screening.” The initial analysis included cohort studies that assessed prevalence of colorectal cancer (CRC) in patients with breast cancer. Subsequent analysis focused on case-control studies that assessed prevalence of advanced colonic adenomas and/or cancer in patients with breast cancer. We used Comprehensive Meta-Analysis (CMA, Version 3, Biostat, Inc) to perform the statistical analysis including construction of Forest plots, and assessment of heterogeneity and/or publication bias. For cohort studies, results were reported as pooled prevalence rates with 95% confidence intervals (CI). We determined odds ratios (OR) for casecontrol studies using random effects modeling. Subjects with a diagnosis of breast cancer who had undergone subsequent screening colonoscopy examinations after the initial cancer diagnosis were included. Results: The search yielded 93 articles. We included 30 cohort studies and 9 case-control studies in the analysis. The 30 cohort studies included 2,228,229 patients with breast cancer of whom 21353 (0.9%) developed subsequent colorectal cancer. The pooled prevalence rate of CRC was 0.9% (95% CI 0.7-1%, pZ0). There was significant heterogeneity between studies (IZ99%, pZ0.0) but no evidence of publication bias. In the 4 case-control studies (including 17,827 breast cancer patients and 70,242 controls) reporting numbers of patients subsequently diagnosed with CRC, a non-significant increase in CRC was reported for breast cancer patients (OR 1.2, 95% CI 0.4-3.3, pZ0.7). There were 4 case-control studies assessing risk of adenomatous polyps (including 610 patients with breast cancer and 882 controls) demonstrating an increased risk of advanced adenoma that was not statistically significant (OR 1.8, 95% CI 0.9-3.8, pZ0.08) with moderate heterogeneity between studies (IZ70%, pZ0.003) There was insufficient data to perform subgroup analyses on the usage of tamoxifen and subsequent CRC risk or mean patient age for cases compared to controls. Conclusions: The overall rate of colorectal cancer did not appear to be increased in patients with breast cancer. Colorectal cancer screening in these patients should occur according to current society guidelines.

Effect of Obesity and Demographic Factors on Advanced Adenoma Detection Rate Among Type 2 Diabetes Mellitus Patients

Introduction: Adenomatous polyps are known precursors of colorectal cancer (CRC). CRC screening recommendations are for individuals with average risk without consideration of special subgroups like diabetic population. There may not be one best screening algorithm, but optimal strategies need to be defined for different population subgroups. We designed our study to measure the effect of race, gender, age, and obesity on advanced adenoma detection rate (AADR) among diabetes mellitus type 2 (DM2) patients. Methods: The retrospective study involved chart review of DM2 patients undergoing outpatient colonoscopy at our center. Only subjects with screening colonoscopy as an indication were included. Subjects with incomplete colonoscopy or with personal history of CRC, IBD, HNPCC, FAP, or colectomy were excluded. Anesthesia, colonoscopy, and pathology reports were reviewed to collect the data related to age, gender, race, weight, height, polyp, adenoma, and advanced adenoma. Based on BMI, the subjects were grouped into 4 categories (1-BMI<25, 2-BMI-25 to 29.9, 3-BMI-30 to 39.9, 4- BMI 40 and above). Binomial logistic regression model was used to analyze the data. Results: Six hundred twenty-three subjects with male to female ratio of 1:1.3 satisfied the inclusion criteria. Ethnically 69.8% were African Americans (AA), 8.2% Whites (W), 10.4% Hispanics (H), 10% Asians (As) and 1.4 % others. AADR was 11.7% for female and 15.8% for male. AADR was 11.3%, 13.1%, 13.8% and 19.6% for As, AA, H and W respectively. AADR was 10.6% for 50-59 years age group, 17.8% for 60-69 years age group and 13.1% for 70-79 years age group (p-value <.05). AADR for category 1, 2, 3, and 4 was 11.9%, 12.4%, 13.8%, and 17.8% respectively (p-value >.05). Conclusion: Males have higher AADR in comparison to females. Whites have a much higher risk for advanced adenoma in comparison to African Americans, Hispanics and Asians in our population. The risk for advanced adenoma increases with age (till 70 years of age) and then trends down. There is a positive correlation between BMI and AADR. Male gender, Age, White race and Obesity increases the risk for CRC precursor lesions among DM2 patients.