Antioxidant enzyme and DNA base repair genetic risk scores' associations with systemic oxidative stress biomarker in pooled cross-sectional studies.

Oxidative stress is hypothesized to contribute to the pathogenesis of several chronic diseases. Numerous dietary and lifestyle factors are associated with oxidative stress; however, little is known about associations of genetic factors, individually or jointly with dietary and lifestyle factors, with oxidative stress in humans. We genotyped 22 haplotype-tagging single nucleotide polymorphisms (SNPs) in 3 antioxidant enzyme (AE) genes and 79 SNPs in 14 DNA base excision repair (BER) genes to develop oxidative stress-specific AE and BER genetic risk scores (GRS) in two pooled cross-sectional studies ( = 245) of 30-74-year-old, White, cancer- and inflammatory bowel disease-free adults.

Impact of Common Vitamin D-Binding Protein Isoforms on Supplemental Vitamin D3 and/or Calcium Effects on Colorectal Adenoma Recurrence Risk: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Variants in the vitamin D-binding protein (DBP) gene (GC) encode DBP isoforms that may affect vitamin D metabolism. However, whether these isoforms modify the effects of vitamin D3 and/or calcium supplementation on colorectal adenoma recurrence is unclear. We hypothesized that supplementation effects may be stronger among those with the DBP2 isoform (encoded by the rs4588*A allele), which is associated with vitamin D deficiency and modified the associations of circulating vitamin D with risk for colorectal neoplasms in observational studies.

Associations of DNA Base Excision Repair and Antioxidant Enzyme Genetic Risk Scores with Biomarker of Systemic Inflammation.

Inflammation is implicated in the etiology of various aging-related diseases. Numerous dietary and lifestyle factors contribute to chronic systemic inflammation; genetic variation may too. However, despite biological plausibility, little is known about associations of antioxidant enzyme (AE) and DNA base excision repair (BER) genotypes with human systemic inflammation.

Association of an evolutionary-concordance lifestyle pattern score with incident CVD among Black and White men and women.

Dietary and lifestyle evolutionary discordance is hypothesised to play a role in the aetiology of CVD, including CHD and stroke. We aimed to investigate associations of a previously reported, total (dietary plus lifestyle) evolutionary-concordance (EC) pattern score with incident CVD, CHD and stroke. We used multivariable Cox proportional hazards regression to investigate associations of the EC score with CVD, CHD and stroke incidence among USA Black and White men and women ≥45 years old in the prospective REasons for Geographic and Racial Differences in Stroke study (2003-2017).

Associations of dietary and lifestyle inflammation scores with mortality due to CVD, cancer, and all causes among Black and White American men and women.

One potential mechanism by which diet and lifestyle may affect chronic disease risk and subsequent mortality is through chronic systemic inflammation. In this study, we investigated whether the inflammatory potentials of diet and lifestyle, separately and combined, were associated with all-cause, all-CVD and all-cancer mortality risk. We analysed data on 18 484 (of whom 4103 died during follow-up) Black and White men and women aged ≥45 years from the prospective REasons for Geographic and Racial Differences in Stroke study.

Associations of Evolutionary-Concordance Diet and Lifestyle Pattern Scores with Incident, Sporadic Colorectal Adenoma in a Pooled Case-Control Study.

Differences in diet and lifestyle relative to those of our Paleolithic-era ancestors may explain current high incidences of chronic diseases, including colorectal cancer (CRC), in Westernized countries. Previously reported evolutionary-concordance diet and lifestyle pattern scores, reflecting closeness of diet and lifestyle patterns to those of Paleolithic-era humans, were associated with lower CRC incidence. Separate and joint associations of the scores with colorectal adenoma among men and women are unknown.

Associations of dietary, lifestyle, other participant characteristics, and oxidative balance scores with plasma F-isoprostanes concentrations in a pooled cross-sectional study.

Purpose: Plasma F-isoprostanes (FiP) concentration, a reliably measured, valid, systemic oxidative stress biomarker, has been associated with multiple health-related outcomes; however, associations of most individual dietary and lifestyle exposures with FiP are unclear, and there is no reported oxidative balance score (OBS) comprising multiple dietary and/or lifestyle components weighted by their associations with FiP.

Methods: To investigate cross-sectional associations of dietary and lifestyle characteristics with plasma FiP concentrations, we used multivariable general linear models to compare adjusted mean FiP concentrations across categories of dietary nutrient and whole-food intakes and lifestyle characteristics in two pooled cross-sectional studies (n = 386). We also developed equal-weight and weighted OBS (nutrient- and foods-based dietary OBS, lifestyle OBS, and total OBS), and compared adjusted mean FiP concentrations across OBS tertiles.

Dietary and Lifestyle Inflammation Scores Are Inversely Associated with Metabolic-Associated Fatty Liver Disease among Iranian Adults: A Nested Case-Control Study.

Background: Diet and lifestyle may affect risk for metabolic-associated fatty liver disease (MAFLD) by chronically elevating systemic inflammation.

Objectives: In this study we investigated the separate and joint associations of dietary and lifestyle inflammation scores (DIS and LIS, respectively) with MAFLD risk.

Methods: For this nested case-control study we identified and recruited 968 patients with MAFLD (defined as having a fatty liver index ≥60 plus ≥1 of the following conditions: overweight or obese, type II diabetes mellitus, evidence of metabolic dysregulation) and 964 controls from among 35-70-y-old men and women in the baseline phase of the Sabzevar Persian Cohort Study.

Associations of Novel Lifestyle- and Whole Foods-Based Inflammation Scores with Incident Colorectal Cancer Among Women.

Background: Chronic inflammation, associated with lifestyle and dietary factors, may contribute to colorectal carcinogenesis. To address this, we investigated associations of previously validated, inflammation biomarker panel-weighted, novel, 4-component lifestyle (LIS) and 19-component predominately whole foods-based dietary (DIS) inflammation scores with incident colorectal cancer (CRC) in the prospective Iowa Women's Health Study (IWHS; 1986-2012;  = 34,254, of whom 1,632 developed CRC).

Methods: We applied the published scores' components' weights, summed the weighted components to constitute the scores (higher scores reflect a higher balance of pro-inflammatory exposures), and investigated LIS- and DIS-CRC associations using multivariable Cox proportional hazards regression.

Associations of dietary and lifestyle oxidative balance scores with mortality risk among older women: the Iowa Women's Health Study.

Purpose: Substantial basic science evidence suggests that oxidative stress may play a role in aging-related health outcomes, including cardiovascular diseases (CVD) and cancer, and oxidative stress markers were linked with all-cause and cause-specific mortality in epidemiologic studies. However, the associations of many individual dietary and lifestyle anti-/pro-oxidant exposures with mortality are inconsistent. Oxidative balance scores (OBS) that incorporated multiple dietary and lifestyle factors were previously developed and reported to reflect the collective oxidative effects of multiple exposures.

Novel Dietary and Lifestyle Inflammation Scores Directly Associated with All-Cause, All-Cancer, and All-Cardiovascular Disease Mortality Risks Among Women.

Background: Exogenous exposures collectively may contribute to chronic, low-grade inflammation and increase risks for major chronic diseases and mortality. We previously developed, validated, and reported a novel, FFQ-based and lifestyle questionnaire-based, inflammation biomarker panel-weighted, predominantly whole foods-based 19-component dietary inflammation score (DIS) and 4-component lifestyle inflammation score (LIS; comprising physical activity, alcohol intake, BMI, and current smoking status). Both scores were more strongly associated with circulating biomarkers of inflammation in 3 populations than were previously reported dietary inflammation indices.

A novel evolutionary-concordance lifestyle score is inversely associated with all-cause, all-cancer, and all-cardiovascular disease mortality risk.

Purpose: Evolutionary discordance may contribute to the high burden of chronic disease-related mortality in modern industrialized nations. We aimed to investigate the associations of a 7-component, equal-weight, evolutionary-concordance lifestyle (ECL) score with all-cause and cause-specific mortality.

Methods: Baseline data were collected in 2003-2007 from 17,465 United States participants in the prospective REasons for Geographic and Racial Differences in Stroke (REGARDS) study.

Sucrose Intakes and Incident Colorectal Cancer Risk among Women.

Background: High sucrose intakes are hypothesized to increase colorectal cancer (CRC) risk by several mechanisms, and sucrose intakes have been consistently positively associated with CRC risk in case-control studies. However, all but one prospective study reported a null sucrose-CRC association. The only prospective study to report a positive association was the Iowa Women's Health Study (IWHS) of 35,221 cancer-free Iowa women, aged 55 - 69 years old at baseline in 1986, after four years of follow up.

Effects of Supplemental Calcium and Vitamin D on Circulating Biomarkers of Gut Barrier Function in Patients with Colon Adenoma: A Randomized Clinical Trial.

Gut barrier dysfunction promotes chronic inflammation, contributing to several gastrointestinal diseases, including colorectal cancer. Preliminary evidence suggests that vitamin D and calcium could prevent colorectal carcinogenesis, in part, by influencing gut barrier function. However, relevant human data are scarce.

Dietary and Lifestyle Oxidative Balance Scores and Incident Colorectal Cancer Risk among Older Women; the Iowa Women's Health Study.

Background: Basic science literature strongly supports a role of oxidative stress in colorectal cancer (CRC) etiology, but in epidemiologic studies, associations of most individual exposures with CRC have been weak or inconsistent. However, recent epidemiologic evidence suggests that the collective effects of these exposures on oxidative balance and CRC risk may be substantial.

Methods: Using food frequency and lifestyle questionnaire data from the prospective Iowa Women's Health Study (1986-2012), we investigated associations of 11-component dietary and 4-component lifestyle oxidative balance scores (OBS) with incident CRC using multivariable Cox proportional hazards regression.

Inflammation Modulation by Vitamin D and Calcium in the Morphologically Normal Colorectal Mucosa of Patients with Colorectal Adenoma in a Clinical Trial.

Increased COX-2 and decreased 15-hydroxyprostaglandin dehydrogenase (15-HPGD) expression promote prostaglandin-mediated inflammation and colorectal carcinogenesis. Experimental studies suggest that vitamin D and calcium may inhibit these pathways, but their effects on colorectal tissue COX-2 and 15-HPGD expression in humans are unknown. We tested the effects of supplemental vitamin D (1,000 IU/day) and/or calcium (1,200 mg/day) on COX-2 and 15-HPGD expression in the morphologically normal rectal mucosa from 62 paients with colorectal adenoma in a placebo-controlled chemoprevention trial.

Associations of Novel Dietary and Lifestyle Inflammation Scores with Incident, Sporadic Colorectal Adenoma.

Background: Colorectal carcinogenesis is mechanistically linked to inflammation and is highly associated with diet and lifestyle factors that may affect chronic inflammation. We previously developed dietary (DIS) and lifestyle (LIS) inflammation scores, comprising inflammation biomarker-weighted components, to characterize the collective contributions of 19 food groups and four lifestyle exposures to systemic inflammation. Both scores were more strongly directly associated with circulating inflammation biomarkers in three validation populations, including a subset of the study population described below, than were the previously reported dietary inflammatory index and empirical dietary inflammatory pattern.

Associations of Novel Dietary and Lifestyle Inflammation Scores With Incident Colorectal Cancer in the NIH-AARP Diet and Health Study.

Background: Chronically higher inflammation, likely contributed to by dietary and lifestyle exposures, may increase risk for colorectal cancer (CRC). To address this, we investigated associations of novel dietary (DIS) and lifestyle (LIS) inflammation scores with incident CRC in the prospective National Institutes of Health-American Association of Retired Persons Diet and Health Study (N = 453 465).

Methods: The components of our previously developed and externally validated 19-component DIS and 4-component LIS were weighted based on their strengths of associations with a panel of circulating inflammation biomarker concentrations in a diverse subset (N = 639) of participants in the REasons for Geographic and Racial Differences in Stroke Study cohort.

Association of prediagnostic vitamin D status with mortality among colorectal cancer patients differs by common, inherited vitamin D-binding protein isoforms.

Lower prediagnostic circulating 25-hydroxyvitamin D (25[OH]D)-considered the best marker of total vitamin D exposure-is associated with higher mortality risk among colorectal cancer (CRC) patients. However, it is unknown whether this association differs by the vitamin D-binding protein (GC) isoform Gc2 (encoded by GC rs4588*C>A, Thr436Lys), which may substantially affect vitamin D metabolism and modify associations of 25(OH)D with colorectal neoplasm risk. Prediagnostic 25(OH)D-mortality associations according to Gc2 isoform were estimated using multivariable Cox proportional hazards regression among 1281 CRC cases (635 deaths, 483 from CRC) from two large prospective cohorts conducted in the United States (Cancer Prevention Study-II) and Europe (European Prospective Investigation into Cancer and Nutrition).

Association of Circulating Vitamin D With Colorectal Cancer Depends on Vitamin D-Binding Protein Isoforms: A Pooled, Nested, Case-Control Study.

Background: Higher circulating 25-hydroxyvitamin-D [25(OH)D] concentrations are consistently inversely associated with colorectal cancer (CRC) risk in observational studies. However, it is unknown whether this association depends on the functional rs4588*A (Thr436Lys) variant encoding the vitamin D-binding protein-2 (DBP2) isoform, which may affect vitamin D status and bioavailability.

Methods: We analyzed data from 1710 incident CRC cases and 1649 incidence-density-matched controls nested within three prospective cohorts of mostly Caucasians.

Development and Validation of Novel Dietary and Lifestyle Inflammation Scores.

Background: Chronically higher inflammation, which may partly result from diet and lifestyle, is implicated in risk for multiple chronic diseases. The dietary inflammatory index (DII) and empirical dietary inflammatory pattern (EDIP), developed to characterize dietary contributions to systemic inflammation, have several limitations. There are no scores to characterize contributions of lifestyle to inflammation.

Effects of supplemental calcium and vitamin D on tight-junction proteins and mucin-12 expression in the normal rectal mucosa of colorectal adenoma patients.

The physical gut barrier, comprised of a thick mucus layer and the epithelium, plays an important role in defense against microbes and foreign antigens. Calcium and vitamin D may be involved in maintaining the integrity of the intestinal mucosal barrier, the dysfunction of which may lead to endotoxemia and inflammation, and contribute to colorectal carcinogenesis. We investigated supplemental calcium (1200 mg, daily) and/or vitamin D (1000 IU daily) effects on intestinal barrier function-related biomarkers in a subset of 105 participants from a large colorectal adenoma recurrence chemoprevention clinical trial.

Associations of calcium and dairy product intakes with all-cause, all-cancer, colorectal cancer and CHD mortality among older women in the Iowa Women's Health Study.

Ca and dairy product intakes may be inversely associated with all-cause and cause-specific mortality, and non-Ca components of dairy products, such as insulin-like growth factor-1, may be independently associated with mortality. We investigated associations of Ca and dairy product intakes with all-cause, all-cancer, colorectal cancer (CRC) and CHD mortality among 35 221 55- to 69-year-old women in the prospective Iowa Women's Health Study, who were cancer-free in 1986. We assessed diet using a Willett FFQ, and associations using multivariable Cox proportional hazards regression.

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.