A Protective Role for Arachidonic Acid Metabolites against Advanced Colorectal Adenoma in a Phase III Trial of Selenium

Oxylipins derived from arachidonic acid (ARA) have been implicated in the development of colorectal adenomas and colorectal cancer. The primary purpose of this work was to determine the relationship between plasma levels of oxylipins and colorectal adenoma characteristics at study entry, as well as with the development of a new adenoma during follow-up within a Phase III adenoma prevention clinical trial with selenium (Sel). Secondarily, we sought to determine whether the selenium intervention influenced plasma oxylipin levels. Four oxylipins were quantified in stored plasma samples from a subset of Sel study subjects (n = 256) at baseline and at 12-months. There were significantly lower odds of an advanced adenoma at baseline with higher prostaglandin E2 (PGE2), with an OR (95% CI) of 0.55 (0.33–0.92), and with 5-hydroxyeicosatetraenoic acid (5-HETE) ((0.53 (0.33–0.94)); and of a large adenoma with higher PGE2 ((0.52 (0.31–0.87)). In contrast, no associations were observed between any oxylipin and the development of a new adenoma during follow-up. Selenium supplementation was associated with a significantly smaller increase in 5-HETE after 12 months compared to the placebo, though no other results were statistically significant. The ARA-derived oxylipins may have a role in the progression of non-advanced adenoma to advanced, but not with the development of a new adenoma.

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Regulation of canine platelet function II. Catecholamines

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1983.245.1.r100 ◽

1983 ◽

Vol 245 (1) ◽

pp. R100-R109 ◽

Cited By ~ 1

Author(s):

K. M. Meyers ◽

L. Y. Huston ◽

R. M. Clemmons

Keyword(s):

Arachidonic Acid ◽

Adrenergic Receptor ◽

Dense Granule ◽

Platelet Response ◽

Receptor Agonists ◽

Alpha Adrenergic Receptor ◽

Acid Metabolites ◽

Induced Aggregation ◽

The Relationship ◽

Platelet Shape

The action of epinephrine (E) on canine platelet aggregation is described. Although E did not induce a change in platelet shape or aggregation, potentiation of aggregation induced by the following agents was observed at physiological E concentrations (that is, less than 10 nM/1): arachidonic acid; the dense granule agonists, ADP and serotonin (5-HT); and collagen. Epinephrine-induced potentiation was in part independent of formation of arachidonic acid metabolites, and E potentiated the aggregating action of the bivalent cationophore A23187. Potentiation was inhibited by alpha-adrenergic receptor antagonists phenoxybenzamine, phentolamine, and ergotamine, and mimicked by alpha-adrenergic receptor agonists norepinephrine, clonidine, and in some cases, phenylephrine. The beta-adrenergic receptor agonists isoproterenol and dobutamine inhibited ADP-induced aggregation, and this action was presented by pretreating the platelets with propranolol and dichloroisoproterenol. An augmentation of the aggregation response of platelets to arachidonic acid was observed in blood samples withdrawn when circulating catecholamines were elevated. The physiological implication of epinephrine acting as a gain controller that alters the relationship between actuating signal and the platelet response to an agonist is discussed.

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Colorectal Adenoma Risk Is Increased among Recently Diagnosed Adult Celiac Disease Patients

Gastroenterology Research and Practice ◽

10.1155/2018/6150145 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5

Author(s):

Juan Lasa ◽

Astrid Rausch ◽

Luis Florez Bracho ◽

Josefina Altamirano ◽

Daniela Speisky ◽

...

Keyword(s):

Celiac Disease ◽

Colorectal Adenoma ◽

Colorectal Neoplasia ◽

Adult Patients ◽

Colorectal Adenomas ◽

Screening Colonoscopy ◽

Advanced Adenoma ◽

Adenoma Detection ◽

Adult Celiac Disease ◽

Recent Diagnosis

Background. The association between celiac disease and colorectal neoplasia has been previously studied, but the question whether recently diagnosed celiac patients show an increased colorectal adenoma prevalence remains unanswered. Aims. To compare the prevalence of colorectal adenomas between adult patients with a recent diagnosis of celiac disease versus healthy controls. Materials and Methods. A retrospective case-control study was undertaken. Patients with a diagnosis of celiac disease at an age of 45 years or more who undertook colonoscopy six months before or six months after the initiation of a gluten-free diet were enrolled as cases. Asymptomatic subjects undertaking screening colonoscopy were recruited as controls in a 2 : 1 fashion. The prevalence of colorectal adenomas and the prevalence of advanced adenomas were compared between groups. Results. 57 celiac disease patients and 118 controls were enrolled. There was a greater prevalence of female patients among the celiac group, with no significant differences in terms of age. There were more obese patients among controls and a higher proportion of tabaquism among celiac patients. Adenoma prevalence was significantly higher among celiac patients (47.37% versus 27.97%, p=0.01). Advanced adenoma detection was not different between groups. Conclusion. Adult patients with a recent diagnosis of celiac disease have an increased prevalence of colorectal adenomas.

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Risk factors of colorectal adenoma recurrence among individuals under 50 years of age compared to those 50 years of age or older.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.1554 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 1554-1554

Author(s):

Christine Louise Sardo Molmenti ◽

Jingyan Yang ◽

Cynthia A Thomson ◽

Elizabeth A Hibler ◽

Gloria Ho ◽

...

Keyword(s):

Risk Factors ◽

Colorectal Adenoma ◽

Colorectal Adenomas ◽

Age Group ◽

Current Smoking ◽

Adenoma Recurrence ◽

Younger Age ◽

History Of ◽

Colorectal Adenoma Recurrence

1554 Background: Colorectal cancer incidence and mortality are increasing among individuals < 50 years of age. Data are limited regarding the epidemiology of colorectal adenomas in this younger age group. This study investigated and compared risk factors associated with recurrence of adenomas in individuals under and over 50 years of age. Methods: Pooled analyses from the Wheat Bran Fiber and Ursodeoxycholic Acid phase III, randomized, controlled clinical trials included 1,623 participants, aged 40-80 years. Each completed baseline questionnaires related to family history and lifestyle habits, had one or more colorectal adenomas removed at baseline, and had a follow-up colonoscopy during the trial (mean follow up 36 months). Univariate and multivariate logistic regression modeling estimated the association between age and colorectal adenoma recurrence, and evaluate multiple risk factors, while controlling for confounding factors. Results: A statistically significant increased trend was found for colorectal adenoma recurrence with increasing age ( Ptrend= < 0.001). Multivariate logistic regression revealed that risk factors significantly associated with adenoma recurrence in the ≥50 age group (n = 1,523) included history of previous polyps, characteristics of adenomas removed at baseline (multiple adenomas and villous feature), current smoking, and an increased waist circumference. Although risk profile in the < 50 age group (n = 95) shared similarities with that in the ≥50 age group (e.g., current smoking), there were a few notable differences: history of previous polyps was a more prominent predictor for recurrence for the < 50 (OR< 50 = 4.76 and OR≥50 = 1.33, Pinteraction = 0.042), whereas baseline characteristics of adenomas were more important for the ≥50 (multiple adenomas: OR< 50 = 0.40 and OR≥50 = 2.28, Pinteraction = 0.043). Conclusions: Predisposition to colorectal adenoma is a more important risk factor for recurrence in the < 50 as compared to the ≥50. Future studies need to identify susceptibility factors contributing to the increasing incidence of colorectal cancer in this younger age group.

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Fecal Metabolomic Signatures in Colorectal Adenoma Patients Are Associated with Gut Microbiota and Early Events of Colorectal Cancer Pathogenesis

mBio ◽

10.1128/mbio.03186-19 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 8

Author(s):

Minsuk Kim ◽

Emily Vogtmann ◽

David A. Ahlquist ◽

Mary E. Devens ◽

John B. Kisiel ◽

...

Keyword(s):

Colorectal Cancer ◽

Gut Microbiota ◽

Colorectal Adenoma ◽

Precancerous Lesions ◽

Colorectal Adenomas ◽

Advanced Adenoma ◽

Bioactive Lipids ◽

Gut Microbes ◽

Cancer Pathogenesis ◽

Composition Profiles

ABSTRACT Colorectal adenomas are precancerous lesions of colorectal cancer (CRC) that offer a means of viewing the events key to early CRC development. A number of studies have investigated the changes and roles of gut microbiota in adenoma and carcinoma development, highlighting its impact on carcinogenesis. However, there has been less of a focus on the gut metabolome, which mediates interactions between the host and gut microbes. Here, we investigated metabolomic profiles of stool samples from patients with advanced adenoma (n = 102), matched controls (n = 102), and patients with CRC (n = 36). We found that several classes of bioactive lipids, including polyunsaturated fatty acids, secondary bile acids, and sphingolipids, were elevated in the adenoma patients compared to the controls. Most such metabolites showed directionally consistent changes in the CRC patients, suggesting that those changes may represent early events of carcinogenesis. We also examined gut microbiome-metabolome associations using gut microbiota profiles in these patients. We found remarkably strong overall associations between the microbiome and metabolome data and catalogued a list of robustly correlated pairs of bacterial taxa and metabolomic features which included signatures of adenoma. Our findings highlight the importance of gut metabolites, and potentially their interplay with gut microbes, in the early events of CRC pathogenesis. IMPORTANCE Colorectal adenomas are precursors of CRC. Recently, the gut microbiota, i.e., the collection of microbes residing in our gut, has been recognized as a key player in CRC development. There have been a number of gut microbiota profiling studies for colorectal adenoma and CRC; however, fewer studies have considered the gut metabolome, which serves as the chemical interface between the host and gut microbiota. Here, we conducted a gut metabolome profiling study of colorectal adenoma and CRC and analyzed the metabolomic profiles together with paired microbiota composition profiles. We found several chemical signatures of colorectal adenoma that were associated with some gut microbes and potentially indicative of future CRC. This study highlights potential early-driver metabolites in CRC pathogenesis and guides further targeted experiments and thus provides an important stepping stone toward developing better CRC prevention strategies.

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Prevalence of adenomatous polyposis in a fecal immunochemical test-based colorectal cancer screening program and risk of advanced neoplasia during follow-up

Endoscopy ◽

10.1055/a-1660-5353 ◽

2021 ◽

Author(s):

Sabela Carballal ◽

Ariadna Sánchez ◽

Leticia Moreira ◽

Jesús-Eduardo Cuellar Monterrubio ◽

Julio Bernuy ◽

...

Keyword(s):

Cumulative Incidence ◽

Screening Program ◽

Fecal Immunochemical Test ◽

Colorectal Adenomas ◽

Advanced Adenoma ◽

Multivariable Logistic Regression Analysis ◽

Crc Screening ◽

Advanced Neoplasia ◽

Immunochemical Test

Background and study aims: current guidelines recommend genetic counseling and intensive colonoscopy surveillance for patients with ≥10 colorectal adenomas based on scarce data. We investigated the prevalence of this condition in a FIT (fecal immunochemical test)-based colorectal (CRC) screening program and the incidence of metachronous lesions during follow-up. Patients and methods: we retrospectively included all FIT-positive participants with ≥10 adenomas at index colonoscopy between 2010 and 2018. Surveillance colonoscopies (SVC) were collected until 2019. Patients with inherited syndromes, serrated polyposis syndrome, total colectomy or lacking surveillance data, were excluded. Cumulative incidence of CRC and advanced neoplasia (AN) were analyzed by Kaplan-Meyer analysis. Risk factors of metachronous AN were investigated by multivariable logistic-regression analysis. Results: 215/9,582 (2.2%) participants had ≥10 adenomas. Germline genetic testing was performed in 92% of patients with ≥20 adenomas identifying 2 (3.3%) inherited syndromes. 3-year cumulative incidence of CRC and AN was 1%, and 16%, respectively. In 39 (24.2%) patients no polyps were found at first SVC. The presence of advanced adenoma was independently associated with a higher risk of AN at first SVC (OR: 3.91, 95% confident interval : 1.12-13.62; p=0.03). Beyond the first SVC, the risk of metachronous AN was lower. Conclusions: the prevalence of ≥10 adenomas in a FIT-based CRC screening program is 2.2% and a small proportion of inherited syndromes are detected even amongst those with ≥ 20 adenomas. Low rate of post-colonoscopy CRC is observed and the risk of AN beyond the first SVC tends to progressively decrease throughout successive follow-up.

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PUFA levels in erythrocyte membrane phospholipids are differentially associated with colorectal adenoma risk

British Journal Of Nutrition ◽

10.1017/s0007114517001490 ◽

2017 ◽

Vol 117 (11) ◽

pp. 1615-1622 ◽

Cited By ~ 8

Author(s):

Samara B. Rifkin ◽

Martha J. Shrubsole ◽

Qiuyin Cai ◽

Walter E. Smalley ◽

Reid M. Ness ◽

...

Keyword(s):

Arachidonic Acid ◽

Erythrocyte Membrane ◽

Colorectal Adenoma ◽

Conditional Logistic Regression ◽

Colorectal Polyp ◽

Colorectal Adenomas ◽

Membrane Phospholipids ◽

Increased Risk ◽

Advanced Adenomas ◽

Adenoma Risk

AbstractDietary intake of PUFA has been associated with colorectal neoplasm risk; however, results from observational studies have been inconsistent. Most prior studies have utilised self-reported dietary measures to assess fatty acid exposure which might be more susceptible to measurement error and biases compared with biomarkers. The purpose of this study was to determine whether erythrocyte phospholipid membrane PUFA percentages are associated with colorectal adenoma risk. We included data from 904 adenoma cases and 835 polyp-free controls who participated in the Tennessee Colorectal Polyp Study, a large colonoscopy-based case–control study. Erythrocyte membrane PUFA percentages were measured using GC. Conditional logistic regression was used to calculate adjusted OR for risk of colorectal adenomas with erythrocyte membrane PUFA. Higher erythrocyte membrane percentages of arachidonic acid was associated with an increased risk of colorectal adenomas (adjusted OR 1·66; 95 % CI 1·05, 2·62, Ptrend=0·02) comparing the highest tertile to the lowest tertile. The effect size for arachidonic acid was more pronounced when restricting the analysis to advanced adenomas only. Higher erythrocyte membrane EPA percentages were associated with a trend towards a reduced risk of advanced colorectal adenomas (Ptrend=0·05). Erythrocyte membrane arachidonic acid percentages are associated with an increased risk of colorectal adenomas.

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Predictors of High-Risk Adenoma Occurrence at Surveillance Colonoscopy in Patients Who Undergo Colorectal Adenoma Removal

Digestive Diseases ◽

10.1159/000489925 ◽

2018 ◽

Vol 36 (5) ◽

pp. 354-361 ◽

Cited By ~ 1

Author(s):

Jin Lee ◽

Joo Wan Seo ◽

Ho Chan Sim ◽

Joon Hyuk Choi ◽

Nae-Yun Heo ◽

...

Keyword(s):

High Risk ◽

Old Age ◽

Colorectal Adenoma ◽

Cumulative Incidence ◽

Incidence Rates ◽

Colorectal Adenomas ◽

Age Group ◽

Surveillance Colonoscopy ◽

Adenoma Recurrence

Objectives: Surveillance colonoscopy is recommended after polypectomy because adenoma recurrence is common. The aim of this study was to evaluate the predictors of high-risk adenoma occurrence at surveillance colonoscopy in patients who undergo colorectal adenoma removal and to clarify the association between age and recurrent colorectal adenoma. Methods: This retrospective study included 563 patients who had colorectal adenomas at baseline colonoscopy and who underwent surveillance colonoscopy. The risk factors for recurrent adenoma were evaluated and the 5-year cumulative incidence rates of overall and high-risk adenoma were compared according to age group. Results: During a mean follow-up period of 3.1 years, 305 (54.2%) patients had overall adenoma recurrence, and 80 (14.2%) patients had high-risk adenoma at surveillance colonoscopy. In a multivariate analysis, old age (≥60 years) and presence of multiple adenomas (3 or more) were significantly associated with high-risk adenoma (p = 0.002 and p = 0.006 respectively). The 5-year cumulative incidence rates of high-risk adenoma were 7.4, 16.7, and 24.1% in the < 50, 50–59, and ≥60 years group respectively (p < 0.001). Conclusions: Old age (≥60 years) and presence of multiple adenomas (3 or more) were strongly associated with the occurrence of high-risk adenoma at surveillance colonoscopy. The 5-year cumulative incidence of high-grade adenoma was significantly high in the old age group.

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Dairy intake during adolescence and risk of colorectal adenoma later in life

British Journal of Cancer ◽

10.1038/s41416-020-01203-x ◽

2021 ◽

Author(s):

Katharina Nimptsch ◽

Dong Hoon Lee ◽

Xuehong Zhang ◽

Mingyang Song ◽

Maryam S. Farvid ◽

...

Keyword(s):

Colorectal Cancer ◽

Colorectal Adenoma ◽

Colorectal Adenomas ◽

Colorectal Carcinogenesis ◽

Advanced Adenoma ◽

Anatomical Site ◽

Inverse Association ◽

Dairy Intake ◽

Dairy Consumption ◽

Adenoma Risk

Abstract Background Higher dairy intake during adulthood has been associated with lower colorectal cancer risk. As colorectal carcinogenesis spans several decades, we hypothesised that higher dairy intake during adolescence is associated with lower risk of colorectal adenoma, a colorectal cancer precursor. Methods In 27,196 females from the Nurses’ Health Study 2, aged 25–42 years at recruitment (1989), who had completed a validated high school diet questionnaire in 1998 and undergone at least one lower bowel endoscopy between 1998 and 2011, logistic regression for clustered data was used to calculate odds ratios (ORs) and 95% confidence intervals (CI). Results Colorectal adenomas were diagnosed in 2239 women. Dairy consumption during adolescence was not associated with colorectal adenoma risk (OR highest vs. lowest [≥4 vs. ≤1.42 servings/day] quintile [95% CI] 0.94 [0.80, 1.11]). By anatomical site, higher adolescent dairy intake was associated with lower rectal (0.63 [0.42, 0.95]), but not proximal (1.01 [0.80, 1.28]) or distal (0.97 [0.76, 1.24]) colon adenoma risk. An inverse association was observed with histologically advanced (0.72 [0.51, 1.00]) but not non-advanced (1.07 [0.86, 1.33]) adenoma. Conclusions In this large cohort of younger women, higher adolescent dairy intake was associated with lower rectal and advanced adenoma risk later in life.

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The Risk of Colorectal Adenoma in Nonalcoholic or Metabolic-Associated Fatty Liver Disease

Biomedicines ◽

10.3390/biomedicines9101401 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1401

Author(s):

Ji-Yeon Seo ◽

Jung-Ho Bae ◽

Min-Sun Kwak ◽

Jong-In Yang ◽

Su-Jin Chung ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Hepatic Fibrosis ◽

Colorectal Adenoma ◽

Fatty Liver Disease ◽

Colorectal Adenomas ◽

Metabolic Dysfunction ◽

Advanced Fibrosis ◽

Increased Risk ◽

The Relationship

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease associated with various metabolic disorders. Metabolic dysfunction-associated fatty liver disease (MAFLD) emphasizes metabolic dysfunction in NAFLD. Although the relationship between NAFLD and colorectal adenomas has been suggested, the effect of MAFLD on colorectal adenoma has yet to be investigated. In this study, we examined the relationship between NAFLD/MAFLD and colorectal adenoma in comparison with other metabolic factors. Methods: Examinees who underwent colonoscopy and abdominal ultrasonography on the same day from January 2012 to December 2012 were included. NAFLD was diagnosed according to the findings of ultrasonography. The Fibrosis-4 (FIB-4) index was used as a surrogate marker for advanced hepatic fibrosis. A logistic regression model was used to analyze the risk of NAFLD/MAFLD for colorectal adenoma. Results: The prevalence of NAFLD and MAFLD was 37.5% and 32.8%, respectively. In the multivariate analysis, male sex, older age, diabetes, and smoking increased the risk of colorectal adenoma. NAFLD and MAFLD were the most important risk factors for colorectal adenoma only in females [adjusted odds ratio (OR) 1.43 and 95% confidence interval (CI) 1.01–2.03, and OR 1.55, 95% CI 1.09–2.20, respectively]. NAFLD and MAFLD with an advanced fibrosis index were significantly associated with an increased risk of colorectal adenoma. (NAFLD: OR 1.38, 95% CI, 1.04–1.83, p = 0.027; MAFLD: OR 1.45, 95% CI, 1.13–1.96, p = 0.004, respectively). Conclusion: NAFLD and MAFLD were significantly associated with a higher risk of colorectal adenomas, especially in females. NAFLD and MAFLD with advanced fibrosis were associated with an increased risk of colorectal adenoma. Colonoscopic examinations may be emphasized for patients with NAFLD/MAFLD, for women, or patients with the presence of hepatic fibrosis.

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

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.559 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 559-559

Author(s):

Sun Young Yang ◽

Eun Young Doo ◽

Young Sun Kim ◽

Jung Eun Lee ◽

Jiyoung Youn ◽

...

Keyword(s):

Colorectal Cancer ◽

Risk Factors ◽

Colorectal Adenoma ◽

Red Meat ◽

Fish Intake ◽

Colorectal Adenomas ◽

Advanced Adenoma ◽

Processed Meat ◽

Meat Intake ◽

High Fish

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.

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