Predictors of Incident Serrated Polyps: Results from a Large Multicenter Clinical Trial.

Background: Serrated polyps (SP) are important colorectal cancer precursors, yet their epidemiology is incompletely understood. We measured risk factors for incident sessile-serrated lesions (SSL) and microvesicular (MVHP) and goblet-cell rich (GCHP) hyperplastic polyp subtypes.

Methods: We conducted a cohort study of patients undergoing colonoscopic surveillance nested within a chemoprevention trial.

Circulating Sex Hormones and Risk of Colorectal Adenomas and Serrated Lesions in Men.

Background: Sex hormones have been implicated in the etiology of colorectal neoplasia in women for over 40 years, but there has been very little investigation of the role of these hormones in men.

Methods: Using data from an adenoma chemoprevention trial, we conducted a secondary analysis to examine serum hormone levels [testosterone, androstenedione, DHEA sulfate (DHEAS), and sex hormone binding globulin (SHBG)] and risk of colorectal precursors in 925 men. Multivariable logistic regression models were fit to evaluate adjusted associations between hormone levels and risk of "low-risk" (single tubular adenoma < 1 cm) and "high-risk" lesions (advanced adenoma or sessile serrated adenoma or right-sided serrated polyp or >2 adenomas of any size).

Risk of keratinocyte carcinomas with vitamin D and calcium supplementation: a secondary analysis of a randomized clinical trial.

Background: It is unknown whether dietary supplementation with vitamin D or calcium prevents keratinocyte carcinomas, also known as nonmelanoma skin cancers.

Objectives: This study aimed to determine whether daily vitamin D or calcium supplementation alters the risk of basal cell carcinoma (BCC) or invasive cutaneous squamous cell carcinoma (SCC).

Methods: The Vitamin D/Calcium Polyp Prevention Study is a completed multicenter, double-blind, placebo-controlled, partial 2 × 2 factorial, randomized clinical trial of vitamin D, calcium, or both for the prevention of colorectal adenomas.

Metabolomics Analysis of Aspirin's Effects in Human Colon Tissue and Associations with Adenoma Risk.

Although substantial evidence supports aspirin's efficacy in colorectal cancer chemoprevention, key molecular mechanisms are uncertain. An untargeted metabolomics approach with high-resolution mass spectrometry was used to elucidate metabolic effects of aspirin treatment in human colon tissue. We measured 10,269 metabolic features in normal mucosal biopsies collected at colonoscopy after approximately 3 years of randomized treatment with placebo, 81 or 325 mg/day aspirin from 325 participants in the Aspirin/Folate Polyp Prevention Study.

Folic acid supplementation and risk of colorectal neoplasia during long-term follow-up of a randomized clinical trial.

Background: The Aspirin/Folate Polyp Prevention Study previously found folic acid increased risk of advanced and multiple colorectal adenomas during a surveillance colonoscopy interval starting about 3 y after randomization.

Objective: We conducted secondary analyses to evaluate folic acid effects with additional follow-up after treatment was stopped.

Methods: In total, 1021 participants recently diagnosed with colorectal adenomas were randomly assigned to 1 mg/d of folic acid (n = 516) or placebo (n = 505), with or without aspirin, beginning 6 July 1994.

Body Composition and Aspirin Dose for Colorectal Adenoma Prevention in a Randomized Clinical Trial.

Background: Visceral adiposity is a risk factor for colorectal adenomas, and aspirin is an established chemopreventive agent. Evidence from clinical trials suggests the effectiveness of aspirin at preventing cardiovascular disease and cancer may require higher doses for higher body weight.

Methods: Body mass index, body surface area, fat-free mass, and fat mass were calculated from baseline height and weight in 1,121 participants of the Aspirin/Folate Polyp Prevention Study, a double-blind, placebo-controlled, 3 × 2 factorial randomized clinical trial of low-dose (81 mg/day) or high-dose (325 mg/day) aspirin and/or 1 mg/day folic acid to prevent metachronous colorectal adenomas.

No Evidence for Posttreatment Effects of Vitamin D and Calcium Supplementation on Risk of Colorectal Adenomas in a Randomized Trial.

Vitamin D and calcium supplementation are postulated to have chemopreventive effects against colorectal neoplasia, yet in our previously reported randomized trial, there was no overall efficacy of calcium and/or vitamin D against colorectal adenoma recurrence. It is possible vitamin D and calcium chemopreventive effects are not detectable until beyond the 3- to 5-year follow-up captured in that trial. Accordingly, we explored possible vitamin D and calcium effects on posttreatment (observational) adenoma occurrence.

Body mass index, calcium supplementation and risk of colorectal adenomas.

Calcium supplementation (1,200 mg/day) did not significantly reduce colorectal adenomas in our recent randomized, controlled trial (Vitamin D/Calcium Polyp Prevention Study, VCPPS, 2004-2013) in contrast to our previous trial (Calcium Polyp Prevention Study, CPPS, 1988-1996). To reconcile these findings, we identified participant characteristics that differed between the study populations and modified the effect of calcium supplementation on adenomas or high-risk findings (advanced or multiple adenomas). Compared to the CPPS, more participants in the VCPPS were obese (body mass index (BMI) ≥30 kg/m ; 37.

Calcium and vitamin D supplementation and increased risk of serrated polyps: results from a randomised clinical trial.

Objective: Serrated lesions such as sessile serrated adenomas or polyps (SSA/Ps) are important colorectal cancer precursors, but aetiological factors for these lesions are largely unknown. We aimed to determine the effects of calcium and vitamin D supplementation on the incidence of serrated polyps (SPs) in general and hyperplastic polyps and SSA/Ps specifically.

Design: Participants with one or more adenoma at baseline were randomised to receive 1200 mg/day of elemental calcium, 1000 IU/day of vitamin D, both or neither agent.

Lifestyle and Other Factors Explain One-Half of the Variability in the Serum 25-Hydroxyvitamin D Response to Cholecalciferol Supplementation in Healthy Adults.

Background: Many factors have been associated with serum 25-hydroxyvitamin D [25(OH)D] concentrations in observational studies, with variable consistency. However, less information is available on factors affecting the magnitude of changes in serum 25(OH)D resulting from vitamin D supplementation.

Objective: This study aimed to identify factors associated with the serum 25(OH)D response to supplementation with 1000 IU cholecalciferol/d during the first year of a large, multicenter, randomized, placebo-controlled colorectal adenoma chemoprevention trial.

Randomized controlled trials: who fails run-in?

Background: Early identification of participants at risk of run-in failure (RIF) may present opportunities to improve trial efficiency and generalizability.

Methods: We conducted a partial factorial-design, randomized, controlled trial of calcium and vitamin D to prevent colorectal adenoma recurrence at 11 centers in the United States. At baseline, participants completed two self-administered questionnaires (SAQs) and a questionnaire administered by staff.

Association between adenoma location and risk of recurrence.

Background And Aims: The biological environment varies across the colorectum and may therefore affect neoplastic growth differently in the proximal and distal colon. The aim of the study was to evaluate the risk for recurrent adenomas and their anatomic location based on adenoma location at baseline colonoscopy.

Methods: Data were extracted from 3 adenoma prevention trials (n = 2430).

A Trial of Calcium and Vitamin D for the Prevention of Colorectal Adenomas.

Background: Epidemiologic and preclinical data suggest that higher intake and serum levels of vitamin D and higher intake of calcium reduce the risk of colorectal neoplasia. To further study the chemopreventive potential of these nutrients, we conducted a randomized, double-blind, placebo-controlled trial of supplementation with vitamin D, calcium, or both for the prevention of colorectal adenomas.

Methods: We recruited patients with recently diagnosed adenomas and no known colorectal polyps remaining after complete colonoscopy.

Calcium supplementation increases blood creatinine concentration in a randomized controlled trial.

Background: Calcium supplements are widely used among older adults for osteoporosis prevention and treatment. However, their effect on creatinine levels and kidney function has not been well studied.

Methods: We investigated the effect of calcium supplementation on blood creatinine concentration in a randomized controlled trial of colorectal adenoma chemoprevention conducted between 2004-2013 at 11 clinical centers in the United States.

C-reactive protein and risk of colorectal adenomas or serrated polyps: a prospective study.

Serum C-reactive protein (CRP) is a sensitive marker of systemic inflammation. Because there is a well-recognized relationship between local inflammation and colorectal cancer, we aimed to evaluate whether serum CRP levels were associated with the occurrence of colorectal adenomas and serrated polyps using data from a large adenoma prevention trial. A total of 930 participants with a history of colorectal adenomas were enrolled in a randomized trial of calcium supplementation (1,200 mg/day) for the prevention of colorectal adenomas.

Vitamin D3 supplementation and upper respiratory tract infections in a randomized, controlled trial.

Background: Randomized controlled trials testing the association between vitamin D status and upper respiratory tract infection (URTI) have given mixed results. During a multicenter, randomized controlled trial of colorectal adenoma chemoprevention, we tested whether 1000 IU/day vitamin D(3) supplementation reduced winter episodes and duration of URTI and its composite syndromes, influenza-like illness (ILI; fever and ≥2 of sore throat, cough, muscle ache, or headache) and colds (no fever, and ≥2 of runny nose, nasal congestion, sneezing, sore throat, cough, swollen or tender neck glands).

Methods: The 2259 trial participants were aged 45-75, in good health, had a history of colorectal adenoma, and had a serum 25-hydroxyvitamin D level ≥12 ng/mL.

Constipation and a low-fiber diet are not associated with diverticulosis.

Background & Aims: Asymptomatic diverticulosis is commonly attributed to constipation caused by a low-fiber diet, although evidence for this mechanism is limited. We examined the associations between constipation and low dietary fiber intake with risk of asymptomatic diverticulosis.

Methods: We performed a cross-sectional study that analyzed data from 539 individuals with diverticulosis and 1569 without (controls).

CYP2C9 variants increase risk of colorectal adenoma recurrence and modify associations with smoking but not aspirin treatment.

Purpose: The cytochrome P450 2C9 enzyme (CYP2C9) is involved in metabolism of endogenous compounds, drugs, and procarcinogens. Two common nonsynonymous polymorphisms in CYP2C9 are associated with reduced enzyme activity: CYP2C9*2 (rs1799853, R144C) and CYP2C9*3 (rs1057910, I359L).

Methods: We investigated whether CYP2C9 genotype was associated with risk of colorectal adenoma and/or modified associations with aspirin treatment or cigarette smoking in a cohort of 928 participants in a randomized trial of aspirin chemoprevention.

Variants downstream of the ornithine decarboxylase gene influence risk of colorectal adenoma and aspirin chemoprevention.

Increased mucosal polyamine levels and ornithine decarboxylase (ODC) activity are associated with an increased risk of colorectal neoplasia and aspirin treatment reduces risk. Previous studies suggest that a single-nucleotide polymorphism (SNP) in the promoter of the ODC gene (rs2302615) may be associated with adenoma risk and/or response to aspirin chemoprevention. However, a comprehensive investigation of common genetic variation in the region of ODC gene is lacking.

Folic acid and prevention of colorectal adenomas: a combined analysis of randomized clinical trials.

Observational data suggest that lower folate status is associated with an increased risk of colorectal neoplasia, implying that folate may be useful as a chemopreventive agent. We conducted a combined analysis of three large randomized trials of folic acid supplementation for the prevention of metachronous adenomas in patients with an adenoma history. Participants included 2,632 men and women who had a history of adenomas randomized to either 0.

Baseline plasma total homocysteine and adenoma recurrence: results from a double blind randomized clinical trial of aspirin and folate supplementation.

Background: Elevated plasma total homocysteine (tHcy) is an accepted marker of functional folate deficiency but may have independent effects on colorectal neoplasia risk. It is uncertain whether plasma tHcy is associated with risk at the low levels common in a folate-fortified population.

Methods: Study subjects, about half of whom were recruited after fortification of grain products with folic acid in the United States and Canada, consisted of 871 individuals with a recent history of one or more colorectal adenomas who were randomized to receive either a 1 mg/day folic acid supplement or a placebo within one of three randomly assigned aspirin treatment groups (placebo, 81, or 325 mg/day).