Incidence Of Colorectal Adenomas Research Articles

Abstract 4292: Mitochodrial D-loop polymorphisms are associated with colorectal adenoma risk

Abstract Somatic mutational events in the mitochondria have been detected in adenomatous polyps. However, the contribution of germline variation in the mitochondrial DNA towards risk of colorectal adenomas, well recognized precursor lesions to colorectal cancer, has not been evaluated previously. Hence, we evaluated associations of mitochondrial polymorphisms in the D-loop and non-D loop regions with incident colorectal adenoma in three pooled colonoscopy-based case-control studies (n = 327 colorectal adenoma cases and 420 controls) that used identical methods for case ascertainment and risk factor determination. We sequenced a 1,124 bp fragment to comprehensively identify all genetic variation in the mitochondrial D-loop region, and used the Sequenom platform to genotype 64 previously described tagSNPs in the non-D loop region. We used multivariate unconditional logistic regression to analyze the association between the mitochondrial polymorphisms and colorectal adenoma risk after adjustment for potential confounders. We identified 320 germline mutations in the D-loop region; 30 (9%) had a minor allele frequency (MAF) ≥ 5%. Most of the mutations clustered in the hypervariable regions HV1 (n = 124; 39%) and HV2 (n = 111; 35%) of the D-loop region. Among the nine common polymorphisms (MAF ≥ 5%) in the HV1 region, four polymorphisms (mt16069, mt16278, mt16294, and mt16296) were statistically significantly directly associated with colorectal adenoma risk (odds ratios [OR]: 1.76 - 2.66; p-values: 0.001 - 0.04). In addition, the polyC tract in the HV1 region was inversely associated with colorectal adenoma risk (OR: 0.90; p = 0.03). None of the other polymorphisms in the mitochondrial D-loop region tract was associated with colorectal adenoma risk. After correction for multiple comparisons, none of the mitochondrial tagSNPs in the non-D loop region was associated with colorectal adenoma risk. These findings suggest that polymorphisms in the HV1 region of the mitochondrial D-loop may be associated with colorectal adenoma risk and support further investigation in future studies. Citation Format: Bharat Thyagarajan, Weihua Guan, Veronika Fedirko, Helene Barcelo, Myron D. Gross, Michael Goodman, Roberd M. Bostick. Mitochodrial D-loop polymorphisms are associated with colorectal adenoma risk. [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 4292.

Abstract 1739: Calcium to magnesium intake ratio and colorectal carcinogenesis, results from the Prostate, Lung, Colorectal, and Ovarian cancer screening trial

Abstract Background A recent randomized trial found no effect of calcium supplementation on reducing risk of colorectal adenoma recurrence. However, the role of calcium in carcinogenesis is yet unconfirmed. An earlier trial found calcium treatment only reduced recurrence when the baseline calcium: magnesium intake ratio was <2.6. Nor is it clear whether calcium intake is differentially related to risks of different stages of colorectal carcinogenesis (incident adenoma, adenoma recurrence and incident colorectal cancer). Further, it is unclear if calcium intake or supplementation confers additional protection against incident colorectal cancer in individuals receiving endoscopic screenings. To address these important scientific inquiries, we have conducted analyses within the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. Methods The PLCO is a large, multicenter, population-based randomized trial designed to determine the effects of screening on cancer-related mortality with a median of 12.5 years of follow up. We evaluated the associations between calcium intake and the risks of incident colorectal adenoma (1,147 cases), recurrent adenoma (855 cases) and incident colorectal cancer (697 and 578 cases in intervention and control arms, respectively) among 108,563 PLCO participants aged 55 to 74 years. Odds ratios (OR) and 95% confidence intervals (95%CIs) for incident adenoma and recurrent adenoma, and hazard ratios (HR) and 95%CIs for colorectal cancer incidence were calculated using unconditional logistic regression models and Cox proportional hazard models after adjusting covariates. Results Compared to low calcium intake (<600 mg/day), higher intakes of calcium were not related to a reduced risk of incidence adenoma, but significantly associated with a reduced risk of advanced/multiple adenomas (p for trend, <0.05). Further, the significant inverse association only appeared when calcium:magnesiuim intake ratios between 1.7 and 2.5. No significant association was observed between Ca intake and risk of adenoma recurrence. In the control arm, we found, compared to low calcium intake, higher intakes of calcium were associated with significantly reduced risks of incident colorectal cancer, primarily distal cancer. Again, we found the inverse association may primarily appear in those with calcium:magnesiuim intake ratios between 1.7 and 2.5. In contrast, in the intervention arm (i.e. screening with flexible sigmoidoscopy), overall, we did not find any significant associations. Conclusion Intake of calcium may be more strongly related to reduced risks of incident advanced/multiple adenoma and incident colorectal cancer among those without active screening with flexible sigmoidoscopy than to recurrent adenoma and incident colorectal cancer risks among those with active screening with flexible sigmoidoscopy. Citation Format: Jing Zhao, Xiangzhu Zhu, Martha J. Shrubsole, Todd L. Edwards, Edward L. Giovannucci, Wei Zheng, Qi Dai, PLCO Project Team. Calcium to magnesium intake ratio and colorectal carcinogenesis, results from the Prostate, Lung, Colorectal, and Ovarian cancer screening trial. [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 1739.

Prevalence of colorectal adenoma in patients with multiple gastric adenoma or cancers.

517 Background: It has been reported that patients with single gastric cancer or adenoma are at increased risk of colorectal cancer or adenoma. However, the incidence of colorectal adenoma in patients with multiple gastric neoplasms has not been discussed yet. Methods: We retrospectively analyzed the esophagogastroduodenoscopic and colonoscopic findings as well as the clinicopathologic features between October 2012 and July 2014. The aim of this study was to investigate whether the incidence of colorectal adenoma is higher or not in patients with multiple gastric neoplasms than those with a single gastric neoplasm. Results: A total of 164 patients with gastric neoplasm were divided into two groups whether the number of lesions was single or multiple. Among the 138 patients with single gastric neoplasm, 51 patients performed colonoscopy for surveillance study and 9 patients underwent colonoscopy among the 26 patients with multiple gastric neoplasms. Colorectal adenoma were detected in 58.8% (30/51) of the single gastric neoplasm group, and in 88.8% (8/9) of the multiple gastric neoplasms group (p < 0.001). The mean number of colorectal adenomas was significantly higher in the multiple gastric neoplasm group than in the single group. (4.78 vs. 1.94, p = 0.013). The age, sex, BMI, presence of underlying diseases and the degree of gastric dysplasia were not significantly different between the two groups. Conclusions: The prevalence and the number of colorectal adenoma were significantly higher in patients with multiple gastric neoplasms than in those with single gastric neoplasm. Clinical trial information: KUGH14308-001.

Fruit and vegetable intakes and risk of colorectal cancer and incident and recurrent adenomas in the PLCO cancer screening trial.

The roles of fruits and vegetables in colorectal cancer development are unclear. Few prospective studies have assessed the association with adenoma, a known precursor to colorectal cancer. Our aim was to evaluate the association between fruit and vegetable intake and colorectal cancer development by evaluating the risk of incident and recurrent colorectal adenoma and colorectal cancer. Study participants were identified from the intervention arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Fruit and vegetable intake was measured using a self-reported dietary questionnaire. Total fruit and vegetable intake was not associated with reduced incident or recurrent adenoma risk overall, but a protective association was observed for multiple adenomas (Odds ratio 3rd tertile vs. 1st tertile = 0.61, 95% confidence interval (CI): 0.38, 1.00). Higher fruit and vegetable intakes were associated with a borderline reduced risk of colorectal cancer (Hazard ratio (HR) 3rd tertile vs. 1st tertile = 0.82, 95% CI: 0.67, 1.01), which reached significance amongst individuals with high processed meat intakes (HR = 0.74, 95% CI: 0.55, 0.99). Our results suggest that increased fruit and vegetable intake may protect against multiple adenoma development and may reduce the detrimental effects of high processed meat intakes on colorectal cancer risk.

Dietary fiber intake and risk of colorectal cancer and incident and recurrent adenoma in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Dietary fiber has been associated with a reduced risk of colorectal cancer. However, it remains unclear at which stage in the carcinogenic pathway fiber may act or which food sources of dietary fiber may be most beneficial against colorectal cancer development. The objective was to prospectively evaluate the association between dietary fiber intake and the risk of incident and recurrent colorectal adenoma and incident colorectal cancer. Study participants were identified from the intervention arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Participants received flexible sigmoidoscopy at baseline and 3 or 5 y after. Dietary fiber intake was measured by using a self-reported dietary questionnaire. The colorectal cancer, incident adenoma, and recurrent adenoma analyses were based on 57,774, 16,980, and 1667 participants, respectively. Unconditional logistic regression was used to assess the risk of incident and recurrent adenoma, and Cox proportional hazards models were used to assess the risk of colorectal cancer across categories of dietary fiber intake, with adjustment for potential confounders. Elevated total dietary fiber intake was associated with a significantly reduced risk of incident distal colorectal adenoma (ORhighest vs. lowest tertile of intake: 0.76; 95% CI: 0.63, 0.91; P-trend = 0.003) but not recurrent adenoma (P-trend = 0.67). Although the association was not statistically significant for colorectal cancer overall (HR: 0.85; 95% CI: 0.70, 1.03; P-trend = 0.10), a reduced risk of distal colon cancer was observed with increased total fiber intake (HR: 0.62; 95% CI: 0.41, 0.94; P-trend = 0.03). Protective associations were most notable for fiber originating from cereals or fruit. This large, prospective study within a population-based screening trial suggests that individuals consuming the highest intakes of dietary fiber have reduced risks of incident colorectal adenoma and distal colon cancer and that this effect of dietary fiber, particularly from cereals and fruit, may begin early in colorectal carcinogenesis. This trial was registered at clinicaltrials.gov as NCT01696981.

Abstract A46: Body mass index, waist circumference, and the risk of colorectal adenomas: Black Women's Health Study

Abstract Introduction: Overweight and obesity are independent risk factors for colorectal cancer among men and women. Associations of body mass index (BMI) with colorectal cancer risk are stronger among men than women. Evidence on the association of anthropometric factors with colorectal adenoma is more equivocal, especially among women. It has been suggested that the association of BMI with adenomas is weaker among postmenopausal women as compared to premenopausal women but data on this finding is limited. A recent study among participants in the PLCO trial failed to show an association of BMI with either colorectal adenoma or colorectal cancer risk among men and women. However, it is possible that BMI might not be the most relevant marker of obesity-associated colorectal neoplasia risk among women. A large cohort study of European Caucasian women showed a higher risk of colorectal cancer with waist circumference but not BMI. There are relatively few studies that have investigated multiple measures of obesity as risk factors for colorectal adenoma and cancer among women and none have been adequately powered for these analyses among African American women. We investigated the association of BMI and waist circumference as risk factors for colorectal adenoma among postmenopausal African American women in the Black Women's Health Study. Methods: We conducted a nested case-control study among participants in the Black Women's Health Study - a cohort study of 59,000 women followed biennially since 1995. Cases were defined as women diagnosed with incident colorectal adenoma between 1997 and 2011. Only those adenoma cases verified by medical record review were included. Controls were participants who also underwent lower gastrointestinal endoscopy and in whom no adenoma or other polyp was found. 3 controls were matched to each case based on age and follow-up period. Weight, height, and abdominal circumference were self-reported by participants at baseline. Weight and waist circumference were updated based on self-report every two years. BMI was categorized into 3 categories: 18-24.9 kg/m2 (normal BMI), 25-29.9 kg/ m2 (overweight), and ≥30 kg/ m2 (obese). Waist circumference was categorized in quintiles based on the distribution among controls. Using logistic regression models, we obtained odds ratios (OR) for colorectal adenoma in relation to BMI and waist circumference, adjusting for age, education, physical activity, fruit and vegetable intake, family history of colorectal cancer, smoking, alcohol intake, energy intake, aspirin use, menopausal status, and post-menopausal hormone therapy. Results: There were 915 adenoma cases and 2,745 controls. After adjusting for multiple covariates, neither overweight (OR: 1.10, 95% CI: 0.88-1.38) nor obese (OR: 1.09, 95% CI: 0.85-1.41) African-American women were at increased risk of colorectal adenomas than women with normal BMI. Although women in the fifth quintile of waist circumference were at higher risk of colorectal adenomas than those in the first quintile in age-adjusted models, the OR was no longer significant after multivariate adjustment (OR: 1.25, 95% CI: 0.94, 1.67) . Conclusions: We did not find an association of either BMI or waist circumference with colorectal adenomas among African-American women. Our results support the findings from other studies in primarily White women that showed no association of BMI with colorectal adenoma in women. Although the association of waist circumference with adenoma risk was stronger compared to BMI among African-American women in our study, it was not statistically significant. Further research is needed to confirm these findings, and explore the association of BMI and waist circumference with colorectal adenoma in African-American men. Citation Format: Chiranjeev Dash, Julie R. Palmer, Lynn Rosenberg, Jeffrey Yu, Lucile L. Adams-Campbell. Body mass index, waist circumference, and the risk of colorectal adenomas: Black Women's Health Study. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A46.

Abstract 1889: Paleolithic and Mediterranean diet pattern scores and their associations with biomarkers of inflammation and oxidative balance

Abstract Chronic inflammation is associated with poor diet quality as well as risk for cancer and other chronic diseases. A diet-inflammation association may relate to evolutionary discordance. We investigated associations of two diet pattern scores, the “Paleolithic” and the Mediterranean, with circulating levels of two inflammation-related biomarkers, C-reactive protein (CRP), an acute inflammatory protein, and F2-isoprostanes, a reliable marker of lipid peroxidation in vivo, in a colonoscopy-based, pooled case-control study of incident sporadic colorectal adenomas (N = 646). We created diet scores from responses on a modified Willett food-frequency questionnaire, and measured plasma levels of CRP and F2-isoprostanes by ELISA and GCMS, respectively. Both diet scores were calculated and categorized into quintiles, and their associations with the biomarker levels were estimated using unconditional logistic regression. The multivariable-adjusted odds ratios (OR) comparing those in the highest relative to those in the lowest quintiles of the Paleolithic and Mediterranean diet scores, were, respectively, 0.73 (95% confidence interval [CI] 0.39, 1.36; Ptrend = 0.35) and 0.71 (95% CI 0.36, 1.40; Ptrend = 0.12) for CRP levels, and 0.35 (95% CI 0.17, 0.74; Ptrend <0.01) and 0.64 (95% CI 0.29, 1.40; Ptrend = 0.03) for F2-isoprostanes levels. These findings, which are particularly strong for the inverse Paleolithic diet score-F2-isoprostanes association, suggest that diets that are more “Paleolithic-” or Mediterranean-like may be associated with lower levels of systemic inflammation and oxidative stress. Citation Format: Kristine Whalen, Marji McCullough, W. Dana Flanders, Terryl J. Hartman, Suzanne Judd, Roberd M. Bostick. Paleolithic and Mediterranean diet pattern scores and their associations with biomarkers of inflammation and oxidative balance. [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 1889. doi:10.1158/1538-7445.AM2015-1889

In vitro and in vivo anti-cancer activity of tangeretin against colorectal cancer was enhanced by emulsion-based delivery system

The oral bioavailability and efficacy of citrus polymethoxyflavone, tangeretin, was attenuated by its poor aqueous solubility. An emulsion-based delivery system was utilized to enhance the anti-tumourigenesis activity of tangeretin. The in vitro anti-proliferative activity of tangeretin was first evaluated using methyl thiazol tetrazolium bromide (MTT) test on colonic carcinoma cell lines, HCT116 and HT29. The utilization of emulsion system significantly improved the efficacy of tangeretin at dosing concentrations at 12.5 and 25 µM. The effectiveness of the emulsion system in enhancing the in vivo oral efficacy of tangeretin against colorectal cancer development was also evaluated by azoxymethane/dextran sodium sulphate (AOM/DSS)-induced colitis related colon tumourigenesis model. The tumour incidence, multiplicity, and pathological signs of colorectal adenoma were significantly reduced when tangeretin emulsion was applied. The regulation on tumourigenesis related protein expression was more effective in mice treated with tangeretin emulsion than unformulated suspension. Our finding indicated that emulsion-based delivery system was an effective means to increase the oral efficacy of tangeretin. This study is the first successful demonstration of the effect of delivery system on the oral efficacy of nutraceutical using long-term animal model.

Mo1940 Prevalence and Risk Factors of Colonic Adenomas Among 1133 40-49 Years Old Undergoing Screening Colonoscopy

Growing evidence suggests that metabolic syndrome is not only a cluster of risk factors for cardiovascular disease and type 2 diabetes, but also for some cancer including a colorectal cancer. We have previously shown that insulin resistance, an increased visceral fat, hypoadiponectinemia and low-grade systemic inflammation assessed by serum IL-6 levels are linked to the risk of colorectal adenoma. Recently, it has been reported that chemerin, as a novel adipokine, can act as a chemoattractant for immune cells. And obesity, insulin resistance and inflammation have shown to have elevated serum levels of chemerin. However, the role of chemerin in human colorectal adenoma is still unknown. Therefore, we investigated the relationship between serum chemerin levels and the incidence of colorectal adenoma. Methods: We conducted a total colonoscopy-based cross-sectional case-control study. 76 male individuals with an endoscopically diagnosed colorectal adenoma were enrolled along with 72 age-matched male for our control group. Both cohort groups underwent health checkups, between 2007 and 2009, at Tohoku Central Hospital. Serum levels of chemerin were measured in samples of venous blood obtained from the participants after an overnight fast. The risk for colorectal adenoma was evaluated by logistic regression analysis. Results: In the colorectal adenoma group, the mean levels of serum insulin, fasting, plasma glucose, value of HOMA-IR and HbA1c were higher than those in the control group. There were no differences between the groups in the proportions of current smokers, alcohol consumers, mean BMI, bold pressure and serum triglyceride. The mean concentration of serum chemerin was significantly higher in the colorectal adenoma group than in the control group (791±354 ng/ml vs. 538±401 ng/ml, p<0.001). In multivariate analysis, high chemerin level (above the median) was associated with the incidence of colorectal adenoma (OR 2.9, 95%CI; 1.456.09) after adjustment for age, blood pressure, BMI, triglyceride, HOMA-IR and HbA1c. In conclusion, the present study suggests that increased serum levels of chemerin are positively associated with the incidence of colorectal adenoma in men. Our study indicates that chemerin may play an important role in the development of human colorectal adenoma. To confirm our findings in this study, further replication and research are required to elucidate the underlying the mechanisms. This will enable us to gain a better understanding of the link between metabolic syndrome and colorectal adenoma.

Mo1937 Chemerin As a Risk Factor for Human Colorectal Adenoma

Growing evidence suggests that metabolic syndrome is not only a cluster of risk factors for cardiovascular disease and type 2 diabetes, but also for some cancer including a colorectal cancer. We have previously shown that insulin resistance, an increased visceral fat, hypoadiponectinemia and low-grade systemic inflammation assessed by serum IL-6 levels are linked to the risk of colorectal adenoma. Recently, it has been reported that chemerin, as a novel adipokine, can act as a chemoattractant for immune cells. And obesity, insulin resistance and inflammation have shown to have elevated serum levels of chemerin. However, the role of chemerin in human colorectal adenoma is still unknown. Therefore, we investigated the relationship between serum chemerin levels and the incidence of colorectal adenoma. Methods: We conducted a total colonoscopy-based cross-sectional case-control study. 76 male individuals with an endoscopically diagnosed colorectal adenoma were enrolled along with 72 age-matched male for our control group. Both cohort groups underwent health checkups, between 2007 and 2009, at Tohoku Central Hospital. Serum levels of chemerin were measured in samples of venous blood obtained from the participants after an overnight fast. The risk for colorectal adenoma was evaluated by logistic regression analysis. Results: In the colorectal adenoma group, the mean levels of serum insulin, fasting, plasma glucose, value of HOMA-IR and HbA1c were higher than those in the control group. There were no differences between the groups in the proportions of current smokers, alcohol consumers, mean BMI, bold pressure and serum triglyceride. The mean concentration of serum chemerin was significantly higher in the colorectal adenoma group than in the control group (791±354 ng/ml vs. 538±401 ng/ml, p<0.001). In multivariate analysis, high chemerin level (above the median) was associated with the incidence of colorectal adenoma (OR 2.9, 95%CI; 1.456.09) after adjustment for age, blood pressure, BMI, triglyceride, HOMA-IR and HbA1c. In conclusion, the present study suggests that increased serum levels of chemerin are positively associated with the incidence of colorectal adenoma in men. Our study indicates that chemerin may play an important role in the development of human colorectal adenoma. To confirm our findings in this study, further replication and research are required to elucidate the underlying the mechanisms. This will enable us to gain a better understanding of the link between metabolic syndrome and colorectal adenoma.

Association of gastric hyperplastic polyps with synchronous colorectal neoplasia

Objective To evaluate the association of gastric hyperplastic polyps with colorectal neoplasia. Methods Data of consecutive patients who underwent esophagogastroduodenoscopy(EGD) and colonoscopy between January 2011 and December 2013 were reviewed retrospectively. They were compared with patients without gastric polyps who also underwent EGD in the same period. The relationship between gastric polyps and colorectal neoplasia was analyzed. Results The incidence of colorectal neoplasia in gastric hyperplastic polyps group was higher than that of the control group[24.0%(46/192) VS 10.4%(40/384), P=0.000]. An increased incidence of colorectal adenomas in gastric hyperplastic polyps group was found, but there was no difference in the incidence of colorectal cancer in gastric hyperplastic polyps group and control group[2.1%(4/192) VS 2.3%(9/384), P=1.000]. Stratification analysis suggested that the incidence of colorectal neoplasia in gastric hyperplastic polyps group who aged over 50 was significantly higher than that in the control group[28.5%(43/151) VS 10.6%(29/274), P=0.017], regardless of different genders and the number of gastric hyperplastic polyps. Conclusion The incidence of colorectal neoplasia in gastric hyperplastic polyps has significantly increased, especially in those aged over 50 years, regardless of different genders and the number of gastric hyperplastic polyps. Such patients should undergo colonoscopy to detect colorectal neoplasia. Key words: Gastroscopes; Colonoscopes; Gastric hyperplastic polyps; Colorectal neoplasia

The MIRACLE trial: A randomized, controlled trial comparing green tea extract versus placebo for the prevention of metachronous colon adenomas in a screening population.

TPS786 Background: Prevention of colorectal cancer is a major health care issue. After polypectomy there is an increased risk of polyp recurrence and various means of chemoprevention have been tried to prevent this. NSAIDs have been shown to be effective but confer side effects such as gastrointestinal bleeding. Nutraceuticals such as polyphenols from tea plants have demonstrated remarkable therapeutic and preventive effects in molecular, epidemiological and some clinical trials. However, their value in preventing colorectal polyps has not been demonstrated in a large, randomized trial. The beneficial safety profile of decaffeinated green tea extract and accumulating evidence of its cancer preventive potential justify and require, in our view, a validation of this compound for the nutriprevention of colorectal adenoma. Good accessibility and low costs might render this neutraceutical a top candidate for wider use as nutritional supplement in colon cancer prevention. Methods: Randomized, double blinded, placebo-controlled, multicenter trial. After a one month run-in period with verum, 918 patients (age: 50-80 years) who have undergone polypectomy within the last 6 months will be randomized to receive either decaffeinated green tea extract (containing 150 mg epigallocatechin gallate (EGCG) two times daily) or placebo over a period of three years. Primary outcome: Incidence of metachronous colorectal adenomas (tubulovillous, tubular, villous, serrated lesions) at the 3 year follow-up colonoscopy. Secondary outcomes: Occurrences, number, localization, size and histological subtypes of adenomas, frequency of colorectal carcinoma. In addition, genetic and biochemical biomarkers in blood samples and genetic alterations (Ras, B-raf, microRNAs) in tissue samples of adenomas will be analyzed (biobanking subprojects). Additionally, nutrikinetics and nutrigenetics of EGCG and other catechins will be assessed in healthy volunteers. Patient recruitment has started in November 2011. At September 2014, 785 patients were recruited and 651 patients were randomized. We expect the last patient out in Spring 2018. (Trial identifier NCT01360320) Clinical trial information: NCT01360320.

A prospective evaluation of C-peptide levels and colorectal adenoma incidence

BackgroundObesity is a recognised positive risk factor for colorectal adenoma and colorectal cancer. Obesity is associated with insulin resistance and compensatory hyperinsulinaemia, and circulating insulin and C-peptide, a biomarker of insulin levels, have been positively associated with colorectal cancer risk. However, whether a similar relationship exists for colorectal adenomas, an established colorectal cancer precursor, is unclear. MethodsIn a nested case-control study of 273 colorectal adenoma cases and 355 matched controls from the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, serum C-peptide levels were measured by a chemiluminescent immunometric assay. Multivariable unconditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI) for colorectal adenoma within quartiles of C-peptide. Further, to explore the temporal stability of C-peptide, repeat samples from the incident adenoma cases (n=50) and controls (n=30), over a 5-year period were assayed and the intra-class correlations (ICC) estimated. ResultsIn a multivariable model that included established colorectal adenoma risk factors, C-peptide levels were not associated with colorectal adenoma (Q4 vs. Q1, OR 0.83, 95% CI: 0.52–1.31; P-trend 0.32); similar null associations were observed by gender, by adenoma subsite and for advanced adenomas. Among control participants, the ICC value over a 5-year period was 0.66. ConclusionOur results suggest that higher C-peptide levels were not associated with colorectal adenoma incidence in this study population. Other biological pathways associated with obesity may be more relevant to the early stages of colorectal tumorigenesis.

Inhibitory effect of metformin therapy on the incidence of colorectal advanced adenomas in patients with diabetes.

Background/AimsMetformin use has been associated with decreased colorectal cancer risk and mortality among diabetic patients. Recent research suggests that metformin use may decrease the incidence of colorectal adenomas in diabetic patients with previous colorectal cancer. This study aimed to assess the clinical effect of metformin use on the development of colorectal adenomas in diabetic patients without previous colorectal cancer.MethodsAmong 604 consecutive diabetic patients who underwent colonoscopic surveillance after initial colonoscopy between January 2002 and June 2012, 240 patients without previous colorectal cancer were enrolled in this study and were divided in two groups: 151 patients receiving metformin and 89 patients not receiving metformin. Patient demographics and clinical characteristics as well as the colorectal adenoma incidence rate were retrospectively analyzed.ResultsThe incidence rate of total colorectal adenomas was not different according to metformin use (P=0.349). However, the advanced adenoma incidence rate was significantly lower in the metformin group compared with the non-metformin group (relative risk [RR], 0.09; P=0.011). Metformin use was independently associated with a decreased incidence of advanced colorectal adenomas after adjustment for clinically relevant factors (RR, 0.072; P=0.016). In addition, the cumulative development rate of advanced adenomas during follow-up was significantly lower in the metformin group compared with the non-metformin group (P=0.007).ConclusionsMetformin use in diabetic patients without previous colorectal cancer is associated with a lower risk of advanced colorectal adenomas.

Irritable bowel syndrome and the incidence of colorectal neoplasia: a prospective cohort study with community-based screened population in Taiwan.

Background:We aim to report the prevalence of irritable bowel syndrome (IBS) and elucidate the influence of IBS on the incidence of colorectal neoplasm through a community-screening-based, longitudinal follow-up study.Methods:We enroled 39 384 community residents aged 40 years or older who had participated in a community-based colorectal cancer-screening programme with an immunochemical faecal occult test since 1999. We followed a cohort that was free of colorectal neoplasm (excluding colorectal neoplasm at baseline) to ascertain the incident colorectal neoplasm through each round of screening and used a nationwide cancer registry. Information on IBS was obtained by linking this screened cohort with population-based health insurance claim data. Other confounding factors were also collected via questionnaire or biochemical tests.Results:The overall period prevalence of IBS was 23%, increasing from 14.7% for subjects aged 40–49 years to 43.7% for those aged 70 years and more. After controlling for age, gender and family history of colorectal cancer, screenees who had been diagnosed as having IBS exhibited a significantly elevated level (21% adjusted hazard ratio (HR)=1.21 (95% CI: 1.02–1.42)) of incident colorectal adenoma compared with those who had not been diagnosed with IBS. A similar finding was noted for invasive carcinoma; however, the size of the effect was of borderline statistical significance (adjusted HR=1.20 (95% CI: 0.94–1.53)).Conclusions:IBS led to an increased risk for incident colorectal neoplasm.

Oats and bowel disease: a systematic literature review.

Whole-grain foods such as oats may protect against colorectal cancer and have benefits on inflammatory bowel disease and coeliac disease. The present study aimed to systematically review the literature describing intervention studies that investigated the effects of oats or oat bran on risk factors for bowel disease. A literature search was conducted using Embase, Medline and the Cochrane library, which identified 654 potential articles. Thirty-eight articles describing twenty-nine studies met the inclusion criteria. Two studies carried out in participants with a history of colorectal adenomas found no effects of increased oat-bran intake on indirect risk makers for colorectal cancer. One of two interventions with oat bran in patients with ulcerative colitis showed small improvements in the patients' conditions. Most of the eleven studies carried out in adults with coeliac disease showed no negative effects of uncontaminated oat consumption. The fourteen studies carried out in volunteers with no history of bowel disease suggest that oats or oat bran can significantly increase stool weight and decrease constipation, but there is a lack of evidence to support a specific effect of oats on bowel function compared with other cereals. A long-term dietary intake of oats or oat bran could benefit inflammatory bowel disorders, but this remains to be proven. A protective effect on colorectal adenoma and cancer incidence has not yet been convincingly shown. The majority of patients with coeliac disease could consume up to 100g/d of uncontaminated oats, which would increase the acceptability of, and adherence to, a gluten-free diet.

Incidence of colorectal adenomas: birth cohort analysis among 4.3 million participants of screening colonoscopy.

Most colorectal cancers develop from adenomas. We aimed to estimate sex- and age-specific incidence rates of colorectal adenomas and to assess their potential implications for colorectal cancer screening strategies. Sex- and age-specific incidence rates of colorectal adenomas were derived by a birth cohort analysis using data from 4,322,085 screening colonoscopies conducted in Germany and recorded in a national database in 2003-2012. In addition, cumulative risks of colorectal cancer among colonoscopically neoplasm-free men and women were estimated by combining adenoma incidence rates with previously derived adenoma-colorectal cancer transition rates. Estimated annual incidence in percentage (95% confidence interval) in age groups 55-59, 60-64, 65-69, 70-74, and 75-79 was 2.4 (2.2-2.6), 2.3 (2.1-2.6), 2.4 (2.1-2.6), 2.2 (1.8-2.5), and 1.8 (1.2-2.3) among men, and 1.4 (1.3-1.5), 1.5 (1.4-1.7), 1.6 (1.4-1.8), 1.6 (1.3-1.8), and 1.2 (0.8-1.6) among women. Estimated 10- and 15-year risks of clinically manifest colorectal cancer were 0.1% and 0.5% or lower, respectively, in all groups assessed. Annual incidence rates of colorectal adenomas are below 2.5% and 2% among men and women, respectively, and show little variation by age. Risk of clinically manifest colorectal cancer is expected to be very small within 10 years and beyond after negative colonoscopy for men and women at all ages. The use of rescreening after a negative screening colonoscopy above 60 years of age may be very limited.

Dietary B vitamin and methionine intake and MTHFR C677T genotype on risk of colorectal tumors in Lynch syndrome: the GEOLynch cohort study.

Dietary intake of B vitamins and methionine, essential components of DNA synthesis and methylation pathways, may influence colorectal tumor (CRT) development. The impact of B vitamins on colorectal carcinogenesis in individuals with Lynch syndrome (LS) is unknown but is important given their high lifetime risk of developing neoplasms. The role of MTHFR C677T genotype in modifying these relationships in LS individuals is also unclear. We investigated associations between dietary intakes of folate, vitamins B2, B6, B12, and methionine and CRT development in a prospective cohort study of 470 mismatch repair gene mutation carriers. Dietary intakes were assessed by food frequency questionnaire. Cox regression models with robust sandwich covariance estimation, adjusted for age, sex, physical activity, number of colonoscopies during person-time, NSAID use, and mutual vitamins were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). Analyses were also stratified by MTHFR C677T genotype. During a median person-time of 28.0months, 131 persons developed a CRT. Fifty-one of these persons developed an incident colorectal adenoma, while there were four persons who developed an incident colorectal carcinoma. Compared to the lowest tertile of intake, adjusted HRs (95% CIs) for CRT development in the highest tertile were 1.06 (0.59-1.91) for folate, 0.77 (0.39-1.51) for vitamin B2, 0.98 (0.59-1.62) for vitamin B6, 1.24 (0.77-2.00) for vitamin B12, and 1.36 (0.83-2.20) for methionine. Low vitamin B2 and low methionine intake were statistically significantly associated with an increased risk of CRT in MTHFR 677TT individuals compared to a combined reference of persons with low intake and CC genotype. There was no suggestion that intake of any dietary B vitamin or methionine was associated with CRT development among those with LS.

Oxidative Balance Score, Colorectal Adenoma, and Markers of Oxidative Stress and Inflammation

An oxidative balance score (OBS) that combines pro- and antioxidant exposures was previously reported to be associated with incident sporadic colorectal adenoma. We extend the previous analyses by assessing associations of the OBS and colorectal adenoma with circulating biomarkers of oxidative stress [F2-isoprostanes (FIP) and fluorescent oxidation products (FOP)], and inflammation [C-reactive protein (CRP)]. Using pooled data from two previously conducted colonoscopy-based case-control studies of incident, sporadic colorectal adenoma (n = 365), the OBS was constructed and divided into three approximately equal intervals, with the lowest interval used as the reference. Biomarker levels were dichotomized as "high" versus "low" based on the median values among controls. Multivariable logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). For the OBS-adenoma association, the ORs (95% CIs) for the middle and highest (relative to the lowest) score intervals were 0.81 (0.46-1.43) and 0.39 (0.17-0.89), respectively. The corresponding OBS category-specific ORs (95% CIs) were 0.50 (0.25-1.01) and 0.25 (0.10-0.65) for FIP, 2.01 (1.13-3.75) and 3.48 (1.51-8.02) for FOP, and 0.57 (0.31-1.04) and 0.21 (0.09-0.49) for CRP. The ORs (95% CIs) reflecting associations of adenoma with high levels of FIP, FOP, and CRP were 1.89 (1.08-3.30), 1.82 (1.11-2.99), and 1.45 (0.88-2.40), respectively. As hypothesized, the OBS was inversely associated with colorectal adenoma and circulating FIP and CRP levels. The reason for the unexpected direct OBS-FOP association is unknown. These data support the use of combined measures of pro- and antioxidant exposures in studies of colorectal neoplasia.

Epigenetic Modifications and Cell Signaling Pathways in GI Carcinogenesis and Prevention

Our team is the Innovation Team of Ministry of Education of China. We have bee engaged in studies on pathogenesis mechanism, prevention and treatment. We first established and verified a mathematical model for chronic atrophic gastritis risk screening. We also found that there are abnormal DNA methylation, histone modifications and non-coding RNAs during GI carcinogenesis. The result from RCT indicated that primary prevention with 1 mg d -1 folic acid supplementation could reduce the incidence of colorectal adenoma. Our group has received the National Second Prize for Progress in Science and Technology in 2008.