Association of tea and coffee consumption and biliary tract cancer risk: The Biliary Tract Cancers Pooling Project.

BACKGROUND AND AIMS: Tea and coffee are widely consumed beverages worldwide. We evaluated their association with biliary tract cancer (BTC) incidence. APPROACH AND RESULTS: We pooled data from 15 studies in the Biliary Tract Cancers Pooling Project to evaluate associations between tea and coffee consumption and biliary tract cancer development. We categorized participants as nondrinkers (0 cup/day), moderate drinkers (>0 and <3 cups/day), and heavy drinkers (≥3 cups/day). We estimated multivariable HRs and 95% CIs using Cox models. During 29,911,744 person-years of follow-up, 851 gallbladder, 588 intrahepatic bile duct, 753 extrahepatic bile duct, and 458 ampulla of Vater cancer cases were diagnosed. Individuals who drank tea showed a statistically significantly lower incidence rate of gallbladder cancer (GBC) relative to tea nondrinkers (HR=0.77; 95% CI, 0.64-0.91), and intrahepatic bile duct cancer (IHBDC) had an inverse association (HR=0.81; 95% CI, 0.66-1.00). However, no associations were observed for extrahepatic bile duct cancer (EHBDC) or ampulla of Vater cancer (AVC). In contrast, coffee consumption was positively associated with GBC, with a higher incidence rate for individuals consuming more coffee (HR<3 cups/day =1.29; 95% CI, 1.01-1.66; HR≥3 cups/day =1.49; 95% CI, 1.11-1.99, Ptrend=0.01) relative to coffee nondrinkers. However, there was no association between coffee consumption and GBC when restricted to coffee drinkers. There was little evidence of associations between coffee consumption and other biliary tract cancers. CONCLUSIONS: Tea consumption was associated with a lower incidence of GBC and possibly IHBDC. Further research is warranted to replicate the observed positive association between coffee and GBC.

Plasma metabolomics profiles in Black and White participants of the Adventist Health Study-2 cohort.

BACKGROUND: Black Americans suffer disparities in risk for cardiometabolic and other chronic diseases. Findings from the Adventist Health Study-2 (AHS-2) cohort have shown associations of plant-based dietary patterns and healthy lifestyle factors with prevention of such diseases. Hence, it is likely that racial differences in metabolic profiles correlating with disparities in chronic diseases are explained largely by diet and lifestyle, besides social determinants of health. METHODS: Untargeted plasma metabolomics screening was performed on plasma samples from 350 participants of the AHS-2, including 171 Black and 179 White participants, using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and a global platform of 892 metabolites. Differences in metabolites or biochemical subclasses by race were analyzed using linear regression, considering various models adjusted for known confounders, dietary and/or other lifestyle behaviors, social vulnerability, and psychosocial stress. The Storey permutation approach was used to adjust for false discovery at FDR < 0.05. RESULTS: Linear regression revealed differential abundance of over 40% of individual metabolites or biochemical subclasses when comparing Black with White participants after adjustment for false discovery (FDR < 0.05), with the vast majority showing lower abundance in Blacks. Associations were not appreciably altered with adjustment for dietary patterns and socioeconomic or psychosocial stress. Metabolite subclasses showing consistently lower abundance in Black participants included various lipids, such as lysophospholipids, phosphatidylethanolamines, monoacylglycerols, diacylglycerols, and long-chain monounsaturated fatty acids, among other subclasses or lipid categories. Among all biochemical subclasses, creatine metabolism exclusively showed higher abundance in Black participants, although among metabolites within this subclass, only creatine showed differential abundance after adjustment for glomerular filtration rate. Notable metabolites in higher abundance in Black participants included methyl and propyl paraben sulfates, piperine metabolites, and a considerable proportion of acetylated amino acids, including many previously found associated with glomerular filtration rate. CONCLUSIONS: Differences in metabolic profiles were evident when comparing Black and White participants of the AHS-2 cohort. These differences are likely attributed in part to dietary behaviors not adequately explained by dietary pattern covariates, besides other environmental or genetic factors. Alterations in these metabolites and associated subclasses may have implications for the prevention of chronic diseases in Black Americans.

Proportional troponin changes and risk for outcomes with intervention strategies in non-ST-elevation acute coronary syndrome across kidney function.

AIMS: This analysis evaluates whether proportional serial cardiac troponin (cTn) change predicts benefit from an early versus delayed invasive, or conservative treatment strategies across kidney function in non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: Patients diagnosed with NSTE-ACS in the Veterans Health Administration between 1999 and 2022 were categorized into terciles (<20%, 20 to ≤80%, >80%) of proportional change in serial cTn. Primary outcome included mortality or rehospitalization for myocardial infarction at 6 and 12 months, in survivors of index admission. Adjusted hazard ratio (HR) with 95% confidence Intervals (95% confidence interval [CI]) were calculated for the primary outcome for an early invasive (≤24 h of the index admission), delayed invasive (>24 h of index admission to 90-days postdischarge), or a conservative management. RESULTS: Chronic kidney disease (CKD) was more prevalent (45.3%) in the lowest versus 42.2% and 43% in middle and highest terciles, respectively (p < 0.001). Primary outcome is more likely for conservative versus early invasive strategy at 6 (HR: 1.44, 95% CI: 1.37-1.50) and 12 months (HR: 1.44, 95% CI: 1.39-1.50). A >80% proportional change demonstrated HR (95% CI): 0.90 (0.83-0.97) and 0.93 (0.88-1.00; p = 0.041) for primary outcome at 6 and 12 months, respectively, when an early versus delayed invasive strategy was used, across CKD stages. CONCLUSIONS: Overall, the invasive strategy was safe and associated with improved outcomes across kidney function in NSTE-ACS. Additionally, >80% proportional change in serial troponin in NSTE-ACS is associated with benefit from an early versus a delayed invasive strategy regardless of kidney function. These findings deserve confirmation in randomized controlled trials.

Systemic Lupus Erythematosus and the Ratio of Omega-3 to Omega-6 Fatty Acids Consumption among Women in the Adventist Health Study-2.

OBJECTIVE: To assess the associations of omega-3 and omega-6 fatty acids consumption, and the ratio between the two, with self-reported doctor told Systemic Lupus Erythematosus (SLE) diagnosis. Further, to assess whether initiation of omega-3 supplements intake was related to time/year of SLE diagnosis. METHODS: Data from 42,398 women in the Adventist Health Study-2 cohort were used for this cross-sectional study. Unconditional logistic regression modeling was used for all analyses with the following candidate covariates: age, race, education, smoking, and body mass index (BMI). RESULTS: Compared to non-cases, participants with a diagnosis of SLE reported higher intakes of total omega-3 fatty acids and about the same intakes of omega-6 fatty acids. Overall, they had higher ratios of omega-3 to omega-6 fatty acids. When assessing odds ratios of SLE diagnosis by quartiles of omega-3 to omega-6 and DHA+EPA to omega-6, there was a positive significant trend (p trend = 0.005). Additionally, among those reporting intake of fish oil, 87% had initiated fish oil consumption around the time of SLE diagnosis. SLE was more likely to occur among Black women compared to White women, among ever smokers compared to never smokers, among overweight women compared to women with normal/underweight, and among women 50-59 years compared to those 30-49 year old. When a smaller 6 year follow-up study identified 64 incident SLE cases and assessed their omega-3 intake at baseline (6 years earlier and before the SLE diagnosis) their intake of omega-3 and fish oil was no different than among non-cases. CONCLUSION: We observed a significant positive association between the ratio of omega-3 to omega-6 fatty acids consumption and prevalence of SLE. Among those with prevalent SLE, their year of starting supplementation of omega-3 and fish oil was closely linked to year of SLE diagnosis. Further, baseline intake of omega-3 fatty acids was not increased among 64 incident SLE cases identified during 6 years of follow-up. Our surprising finding can best be explained by reverse causation. This could be an example of how public health information is assimilated and acted upon by a health conscious public.

Left ventricular diastolic abnormalities in vegetarians compared with non-vegetarians.

Vegetarians have less hypertension, diabetes mellitus and obesity, hence possibly lower risk of congestive heart failure (HF). We studied associations between vegetarian diets and echocardiographic markers of stage B HF. In a cross-sectional study, dietary pattern was ascertained by a validated FFQ. Echocardiograms were interpreted using standardised criteria. Participants were free-living subjects in Southern California who were older Adventist Health Study-2 cohort members. After exclusions, 133 subjects aged >60 years were enrolled. Their mean age was 72·7 (sd 8·7) years, 48·1 % were female, 32 % were African American and 71 % were vegetarian. Non-vegetarians had higher body weight (80·3 (sd 15·17) kg v. 71·3 (sd 16·2), P < 0·005), body surface area (1·92 (sd 0·24) m2v. 1·81 (sd 0·22) m2, P = 0·01) and prevalence of hypertension (63 % v. 47 %, P = 0·10). Adjusting for age, sex, race and physical activity, it is found that vegetarians had greater echocardiographic mitral annular e' velocity (a measure of left ventricular (LV) relaxation) 7·44 v. 6·48 (non-vegetarian) cm/s (P = 0·011) and a yet greater contrast when vegans (7·66 cm/s, P = 0·011) were the group of interest. The ratio mid-to-late-diastolic mitral flow velocity (E/A) was also higher in vegans compared with non-vegetarians (1·02 and 0·84, respectively, P = 0·008). Mediation analyses suggested these associations may be partly related to higher blood pressures and BMI in the non-vegetarians. We conclude that vegetarians, especially vegans, appear to have better LV relaxation and fewer diastolic abnormalities than others. As dietary exposure is modifiable, one may speculate pending further investigation about the potential for reduction of stage B HF and later mortality.

Metabolomic profiles of obesity and subgingival microbiome in periodontally healthy individuals: A cross-sectional study.

AIM: Since blood metabolomic profiles of obese individuals are known to be altered, our objective was to examine the association between obesity-related metabolic patterns and subgingival microbial compositions in obese and non-obese periodontally healthy individuals. MATERIALS AND METHODS: Thirty-nine periodontally healthy subjects were enrolled. Based on body mass index scores, 20 subjects were categorized as lean and 19 as obese. A comprehensive periodontal examination was performed. Subgingival plaque and blood samples were collected. Plaque samples were analysed for bacteria using 16S rDNA sequencing. Untargeted metabolomic profiling (mass spectrometry) was used to quantify metabolites in serum. RESULTS: Obese subjects were statistically associated with several periodontopathic taxa including Dialister invisus, Prevotella intermedia, Prevotella denticola, Fusobacterium nucleatum_subsp.vincentii, Mogibacterium diversum, Parvimonas micra and Shuttleworthia satelles. In obese individuals, an amino acid-related metabolic pattern was elevated; however, there was a decrease in metabolic patterns related to lipids and cofactor/vitamins. These metabolic perturbations were associated with multiple subgingival bacterial species that differentiated lean from obese individuals. CONCLUSIONS: Obesity-related perturbations in circulating blood metabolites are associated with the development of periodontopathic bacterial colonization in the subgingival microbiome and consequently may increase the risk for periodontal disease in obese individuals.

Obesity Is Associated with a Weakened Gingival Inflammatory Cytokine Response.

Background and Objectives: An obesity-related elevated body mass index (BMI) across life is associated with chronic low-grade inflammation and increased levels of C-reactive protein (CRP) in blood. CRP is a marker and promoter of inflammation. The objectives of this study were to examine the effect of obesity on the relationship between peripheral and gingival CRP levels and to examine the effects of gingival CRP levels on gingival fluid inflammatory cytokines in periodontitis-resistant obese individuals. Materials and Methods: Thirty-nine participants in good periodontal health were recruited. Twenty patients were classified as lean and nineteen as obese based on their BMI levels. A thorough periodontal assessment was carried out. Gingival crevicular fluid (GCF) and blood samples were collected. Both GCF and blood samples were analyzed for interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-17A (IL-17A), and CRP. Results: GCF CRP levels were significantly higher in the obese than in the lean individuals. No statistically significant differences were noted between the two groups in either GCF or blood in terms of any of the inflammatory cytokine levels. IL-17A was not detected in the GCF of most subjects in both groups. GCF CRP levels were positively associated with blood CRP levels, and the association tended to be stronger in the obese individuals. GCF CRP showed no associations with GCF IL-10 in both groups. Although GCF CRP levels were positively associated with multiple GCF inflammatory cytokines (e.g., IL-1ß, IL-6, IL-8, and TNF-α) in all subjects, the associations tended to be weaker in the obese individuals (e.g., IL-1ß, IL-6, and TNF-α). Furthermore, the levels of the GCF inflammatory cytokines IL-6 and TNF-α were decreased in the obese individuals. Conclusions: Obesity unfavorably influences the relationship between blood and GCF CRP levels and promotes increased CRP levels in GCF. Collectively, the findings suggest a weakened inflammatory cytokine response in the gingival tissues of obese individuals.

Cancer risk in living kidney donors.

Living kidney donors are screened for transmissible diseases including cancer. Outcomes following donation are excellent, but concern exists regarding development of chronic kidney disease, and cancer risk is unknown. We used linked transplant and cancer registry data to identify incident cancers among 84,357 kidney donors in the United States (1995-2017). We compared risk with the general population using standardized incidence ratios (SIRs). For selected cancers, we used Poisson regression to compare donors with 47,451 Adventist Health Study 2 (AHS-2) participants, who typically have healthy lifestyles. During follow-up, 2843 cancers were diagnosed in donors, representing an overall deficit (SIR 0.79, 95%CI 0.76-0.82). None of 46 specified cancer sites occurred in excess relative to the general population, and 15 showed significant deficits (SIR < 1.00). Compared with AHS-2 participants, donors had similar incidence of liver cancer, melanoma, breast cancer, and non-Hodgkin lymphoma but, starting 7 years after donation, elevated incidence of colorectal cancer (adjusted incidence rate ratio 2.07, 95%CI 1.54-2.79) and kidney cancer (2.97, 1.58-5.58, accounting for the presence of a single kidney in donors). Elevated kidney cancer incidence may reflect adverse processes in donors' remaining kidney. Nonetheless, cancer risk is lower than in the general population, suggesting that enhanced screening is unnecessary.

The association between dietary patterns and a doctor diagnosis of systemic lupus erythematosus: the Adventist Health Study-2.

OBJECTIVE: The aim of our study was to assess the association between a diagnosis of Systemic Lupus Erythematosus (SLE) and dietary pattern as well as demographic factors among subjects in the Adventist Health Study-2 (AHS-2) cohort. METHODS: Multivariable logistic regression modeling was used to assess the association between prevalence of self-reported SLE and dietary patterns (vegetarian, pesco-vegetarian and non-vegetarian). Potential confounding variables included were age, gender, race, education, and smoking history among 77,795 AHS-2 participants. RESULTS: There was a dose-response association between the prevalence of SLE with vegetarian diets, ordered by content of animal meats. The stricter vegetarians had 25% lower odds of reporting that they were currently being treated for SLE (OR = 0.75, 95% CI 0.56, 1.02) with intermediate levels for the pesco-vegetarians who eat fish (OR 0.88, 95% CI 0.57, 1.36), compared to non-vegetarians. As expected, there were also significant associations between the prevalence of SLE with sex, race, age, and smoking. Significantly fewer men were diagnosed with SLE compared to women (OR = 0.14, 95% CI: 0.08, 0.22). Compared to non-Hispanic Whites, non-Hispanic Blacks were significantly more likely to report a diagnosis of SLE (OR 1.69, 95% CI 1.29, 2.21). A significantly lower proportion of 30-39 year olds (OR 0.51, 95% CI 0.29, 0.90) reported a diagnosis of SLE when compared to those 60 or older. Also, ever smokers were more likely to report prevalent SLE than those who had never smoked (OR 1.71, 95% CI 1.27, 2.31). CONCLUSION: We found that vegetarians had lower odds of doctor-diagnosed SLE with an increasing trend in prevalence from stricter vegetarians to pesco-vegetarians to non-vegetarians. We also note that the association with other demographic factors in AHS-2 was similar to that found in other studies. Future studies may focus on assessing the incidence and severity of the disease among vegetarians and non-vegetarians.

Glycemic status, non-traditional risk and left ventricular structure and function in the Jackson Heart Study.

BACKGROUND: Left ventricular structure and function abnormalities may be an early marker of cardiomyopathy among African Americans with diabetes (DM) even in the absence of coronary artery disease (CAD), arrhythmia, valvular heart disease and end-stage renal disease (ESRD). This study examined the association of prediabetes (PDM), DM and HbA1c with left ventricular structure and function among Jackson Heart Study (JHS) participants without traditional risk factors. METHODS: Retrospective cross-sectional analyses of the association of PDM, DM and HbA1c with, left ventricular ejection fraction (LV EF), fractional shortening (LV FS), stroke volume index (SVI), cardiac index (CI), left ventricular end diastolic volume index (LVEDVI), left ventricular end systolic volume index (LVESVI), relative wall thickness (RWT), myocardial contraction fraction (MCF) and left ventricular mass index (LVMI). The study was conducted in 2234 adult JHS participants without preexisting CAD, arrhythmia, valvular heart disease or ESRD. Statistical analyses included descriptive, univariate and covariate adjusted linear regression analyses. Sensitivity analyses to explore the impact of hypertension on study outcomes were also carried out. RESULTS: DM compared with no DM was associated with lower, SVI (- 0.96 ml/m2, p = 0.029), LVEDVI (- 1.44 ml/m2 p = 0.015), and MCF (- 1.90% p = 0.007) but higher CI (0.14 L/min/m2, p < 0.001), RWT (0.01 cm, p = 0.002) and LVMI (2.29 g/m2, p = 0.009). After further control for DM duration, only CI remaining significantly higher for DM compared with no DM participants (0.12 L/min/m2, p = 0.009). PDM compared with no PDM was associated with lower, SVI (- 0.87 ml/m2, P = 0.024), LVEDVI (- 1.15 ml/m2 p = 0.003) and LVESVI (- 0.62 ml/m2 p = 0.025). HbA1c ≥ 8.0% compared with HbA1c < 5.7% was associated with lower SVI (- 2.09 ml/m2, p = 0.004), LVEDVI (- 2.11 ml/m2 p = 0.032) and MCF (- 2.94% p = 0.011) but higher CI (0.11 L/min/m2, p = 0.043) and RWT (0.01 cm, p = 0.035). CONCLUSIONS: Glycemic status is associated with important left ventricular structure and function changes among African Americans without prior CAD, arrhythmia, valvular heart disease and ESRD. Longitudinal studies may further elucidate these relationships.

Lower Utilization of Colorectal Cancer Screening Among Vegetarians, Adventist Health Study-2.

This study aims to examine lifestyle predictors of the utilization of colorectal cancer screening. Using modified Poisson regression, we studied self-reported colorectal cancer screening utilization (colonoscopy or fecal occult blood test) with various dietary and lifestyle characteristics among 33,922 subjects aged 51 + years in the Adventist Health Study-2, a large population-based prospective cohort study. According to the multivariable-adjusted models, vegetarians were less likely to report screening: vegans, prevalence ratio (PR) = 0.80 (95% confidence interval 0.77-0.83); lacto-ovo-vegetarians (0.95 [0.93-0.97]); and semi-vegetarians (0.97 [0.94-0.99]) compared to non-vegetarians. Blacks were more likely than non-Blacks to be screened (1.04 [1.02-1.06]) and males were less likely (0.93 [0.92-0.95]) to utilize the screening tests. Older subjects were more likely to be screened, and unmarried and divorced/widowed subjects were less likely to screen. Education, personal income, and BMI were positively associated with screening, with p-value for trend < 0.001 for all three variables. A family history of colorectal cancer was associated with higher screening prevalence (1.15 [1.12-1.17]). Our stratified analyses on race and gender with dietary patterns showed non-Hispanic White vegans (PR = 0.77 [0.74-0.81]) and male vegans (PR = 0.76 [0.72-0.81]) were least likely compliant with colorectal cancer screening (p = 0.009 and p = 0.04, respectively). Vegans may believe that their personal risk for colorectal cancer is low due to their healthy lifestyle, resulting in lack of compliance to colorectal cancer screening. It remains to be seen whether vegans in AHS-2 also experience higher incidence of colorectal cancer or are diagnosed at a later stage.

Cross-sectional comparisons of subgingival microbiome and gingival fluid inflammatory cytokines in periodontally healthy vegetarians versus non-vegetarians.

BACKGROUND: Vegetarian diets are known to reduce inflammation. The objective of this study was to test the hypothesis that reduced inflammation associated with a vegetarian diet would promote a more commensal subgingival bacterial profile. METHODS: A total of 39 periodontally healthy subjects (PD ≤3 mm, bleeding on probing <10%) were enrolled. Dietary intake was assessed by a food frequency questionnaire. A comprehensive periodontal examination was performed. Gingival crevicular fluid (GCF) and subgingival plaque samples were collected. GCF samples were assessed for interleukin-1ß, interleukin-6, interleukin-8, tumor necrosis factor-alpha, and interleukin-10. Plaque samples were analyzed for bacteria using 16S rDNA sequencing on an Illumina platform. GenBank database was used for taxonomy classification. RESULTS: Twenty-three subjects were categorized as vegetarian and 16 non-vegetarians. Clinical periodontal measures and GCF cytokine levels were statistically comparable between the two groups. Measures of microbial richness and alpha diversity were also comparable between the two dietary groups. Vegetarians harbored higher levels of phyla associated with gingival health (Actinobacteria, and Proteobacteria). Two species known to be associated with periodontitis (Mogibacterium timidum and Veillonella rogosae) were prominent in non-vegetarians. Pearson's correlations between GCF inflammatory cytokines and microbial taxa differed between vegetarians and non-vegetarians. In vegetarians, the anti-inflammatory cytokine IL-10 positively correlated with two species known to be associated with periodontal health (Peptidiphaga sp. HMT183 and Rothia aeria). CONCLUSIONS: Diet is directly and indirectly associated with the microbial composition of subgingival plaque. A vegetarian diet may promote a subgingival microbiota associated with periodontal health.

Validation of estimated glycaemic index and glycaemic load, stratified by race, in the Adventist Health Study-2 (AHS-2).

OBJECTIVE: Few studies have validated FFQ estimates of dietary glycaemic index (GI) and load (GL). We investigated how well our estimates of overall GI and GL from FFQs correlate with estimates from repeated 24 h recall data to validate overall GI and GL in the Adventist Health Study-2 (AHS-2). DESIGN: The AHS-2 is a prospective population-based cohort of 95 873 Seventh-day Adventist adult church members enrolled from 2002 to 2007 to investigate diet, cancer and mortality. SETTING: A 204-item FFQ was used to assess race- and gender-specific validity of GI and GL and 24 h recall data, from the calibration sub-study, were used as the reference. PARTICIPANTS: The 734 calibration study participants were randomly selected by church and included approximately equal numbers of blacks and whites but were otherwise similar to the whole cohort with respect to gender, age, education and vegetarian status. RESULTS: The deattenuated correlation coefficients for overall GI ranged from 0·19 (95 % CI -0·06, 0·53) in black men to 0·46 (95 % CI 0·40, 0·60) in black women, with both non-black men and women falling between those values (0·45 (95 % CI 0·35, 0·65) and 0·38 (95 % CI 0·27, 0·57), respectively). GL correlations were somewhat higher for all study participants. When looking at the entire cohort, the deattenuated validity correlation value for overall GI was (r 0·38, 95 % CI 0·36, 0·47) and GL was (r 0·39, 95 % CI 0·34, 0·49). CONCLUSIONS: Our findings support the cautious use of our FFQ in epidemiological studies when assessing associations of overall GI and GL with disease risk. However, observed differences by race should be considered when interpreting results.

Lower rates of cancer and all-cause mortality in an Adventist cohort compared with a US Census population.

BACKGROUND: Previous research suggests that Adventists, who often follow vegetarian diets, live longer and have lower risks for many cancers than others, but there are no national data and little published comparative data for black subjects. METHODS: This study compared all-cause mortality and cancer incidence between the nationally inclusive Adventist Health Study 2 (AHS-2) and nonsmokers in US Census populations: the National Longitudinal Mortality Study (NLMS) and its Surveillance, Epidemiology, and End Results substudy. Analyses used proportional hazards regression adjusting for age, sex, race, cigarette smoking history, and education. RESULTS: All-cause mortality and all-cancer incidence in the black AHS-2 population were significantly lower than those for the black NLMS populations (hazard ratio [HR] for mortality, 0.64; 95% confidence interval [CI], 0.59-0.69; HR for incidence, 0.78; 95% CI, 0.68-0.88). When races were combined, estimated all-cause mortality was also significantly lower in the AHS-2 population at the age of 65 years (HR, 0.67; 95% CI, 0.64-0.69) and at the age of 85 years (HR, 0.78; 95% CI, 0.75-0.81), as was cancer mortality; this was also true for the rate of all incident cancers combined (HR, 0.70; 95% CI, 0.67-0.74) and the rates of breast, colorectal, and lung cancers. Survival curves confirmed the mortality results and showed that among males, AHS-2 blacks survived longer than white US subjects. CONCLUSIONS: Substantially lower rates of all-cause mortality and cancer incidence among Adventists have implications for the effects of lifestyle and perhaps particularly diet on the etiology of these health problems. Trends similar to those seen in the combined population are also found in comparisons of black AHS-2 and NLMS subjects.

Associations between reproductive factors and biliary tract cancers in women from the Biliary Tract Cancers Pooling Project.

BACKGROUND & AIMS: Gallbladder cancer (GBC) is known to have a female predominance while other biliary tract cancers (BTCs) have a male predominance. However, the role of female reproductive factors in BTC etiology remains unclear. METHODS: We pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study. RESULTS: During 21,681,798 person-years of follow-up, 875 cases of GBC, 379 of intrahepatic bile duct cancer (IHBDC), 450 of extrahepatic bile duct cancer (EHBDC), and 261 of ampulla of Vater cancer (AVC) occurred. High parity was associated with risk of GBC (HR ≥5 vs. 0 births 1.72; 95% CI 1.25-2.38). Age at menarche (HR per year increase 1.15; 95% CI 1.06-1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13; 95% CI 1.04-1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19; 95% CI 1.09-1.31) and EHBDC (HR 1.11; 95% CI 1.01-1.22) in Asian women only. CONCLUSION: We observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest that sex hormones have distinct effects on cancers across the biliary tract that vary by geography. LAY SUMMARY: Our findings show that the risk of gallbladder cancer is increased among women who have given birth (especially women with 5 or more children). In women from Asian countries, later age at menarche increases the risk of gallbladder cancer, intrahepatic bile duct cancer and extrahepatic bile duct cancer. We did not see this same association in women from Western countries. Age at menopause was not associated with the risk of any biliary tract cancers.

Tomato consumption and intake of lycopene as predictors of the incidence of prostate cancer: the Adventist Health Study-2.

PURPOSE: Studies have controversially suggested that prostate cancer, the most common cancer among Western men, is less common among those with a high intake of tomato products and lycopene. We examine multivariable associations between the intake of tomatoes and lycopene, and risk of prostate cancer. METHODS: In a prospective study of 27,934 Adventist men without prevalent cancer, Cox proportional hazard regression analyses were used to address the objectives. Dietary measurement error was partially corrected with regression calibration. RESULTS: 1226 incident cases of prostate cancer, 355 of them aggressive, were identified during 7.9 years of follow-up. Consumption of canned and cooked tomatoes more than four times a week was associated with a HR = 0.72 (95% CI 0.55, 0.94, P = 0.02) comparing to risk in those never consuming this food. Treating this as a continuous variable, adjusting for confounders, produces a similar result, HR = 0.86 (95% CI 0.75, 0.99), comparing 64 g/day with zero intakes (questionnaire data). Regression calibration, although less precise, suggests a yet stronger and statistically significant inverse relationship, comparing a 24-h dietary recall intake of 71 g/day canned and cooked tomato product, with zero intake. Uncalibrated multivariable-adjusted competing risk analyses do not find differences in tomato associations between aggressive and non-aggressive prostate cancers although power for aggressive cancers is limited. CONCLUSION: Consumption of canned and cooked tomatoes may reduce the risk of prostate cancer. These products contain more available lycopene. However, an observational study cannot exclude confounding by some unidentified, prostate cancer preventive factor. Clinical Trial Registry: ClinicalTrials.gov Identifier: NCT03615599.

Ovarian cancer risk factors by tumor aggressiveness: An analysis from the Ovarian Cancer Cohort Consortium.

Ovarian cancer risk factors differ by histotype; however, within subtype, there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and death, independent of histology. Among 1.3 million women from 21 prospective cohorts, 4,584 invasive epithelial ovarian cancers were identified and classified as highly aggressive (death in <1 year, n = 864), very aggressive (death in 1 to < 3 years, n = 1,390), moderately aggressive (death in 3 to < 5 years, n = 639), and less aggressive (lived 5+ years, n = 1,691). Using competing risks Cox proportional hazards regression, we assessed heterogeneity of associations by tumor aggressiveness for all cases and among serous and endometrioid/clear cell tumors. Associations between parity (phet = 0.01), family history of ovarian cancer (phet = 0.02), body mass index (BMI; phet ≤ 0.04) and smoking (phet < 0.01) and ovarian cancer risk differed by aggressiveness. A first/single pregnancy, relative to nulliparity, was inversely associated with highly aggressive disease (HR: 0.72; 95% CI [0.58-0.88]), no association was observed for subsequent pregnancies (per pregnancy, 0.97 [0.92-1.02]). In contrast, first and subsequent pregnancies were similarly associated with less aggressive disease (0.87 for both). Family history of ovarian cancer was only associated with risk of less aggressive disease (1.94 [1.47-2.55]). High BMI (≥35 vs. 20 to < 25 kg/m2 , 1.93 [1.46-2.56] and current smoking (vs. never, 1.30 [1.07-1.57]) were associated with increased risk of highly aggressive disease. Results were similar within histotypes. Ovarian cancer risk factors may be directly associated with subtypes defined by tumor aggressiveness, rather than through differential effects on histology. Studies to assess biological pathways are warranted.

Plasma, Urine, and Adipose Tissue Biomarkers of Dietary Intake Differ Between Vegetarian and Non-Vegetarian Diet Groups in the Adventist Health Study-2.

BACKGROUND: Differences in food composition, nutrient intake, and various health outcomes have been reported for vegetarians and non-vegetarians in the Adventist Health Study-2 (AHS-2) cohort. OBJECTIVE: We sought to determine whether biomarkers of dietary intake also differed between individuals classified as vegetarian (vegan, lacto-ovo-vegetarian, pesco-vegetarian, semi-vegetarian) and non-vegetarians based on patterns of consumption of meat, dairy, and eggs. METHODS: Fasting plasma, overnight urine, and adipose tissue samples were collected from a representative subset of AHS-2 participants classified into 5 diet groups (vegan, lacto-ovo-vegetarian, pesco-vegetarian, semi-vegetarian, non-vegetarian) who also completed food-frequency questionnaires. Diet-related biomarkers including carotenoids, isoflavones, enterolactone, saturated and polyunsaturated fatty acids, and vitamins were analyzed in 840 male and female participants. Multiple linear regression was used to examine the association between diet pattern and biomarker abundance, comparing each of 4 vegetarian dietary groups to non-vegetarians, and adjusted mean values were calculated. Bonferroni correction was applied to control for multiple testing. RESULTS: Vegans had higher plasma total carotenoid concentrations (1.6-fold, P < 0.0001), and higher excretion of urinary isoflavones (6-fold, P < 0.0001) and enterolactone (4.4-fold) compared with non-vegetarians. Vegans had lower relative abundance of saturated fatty acids including myristic, pentadecanoic, palmitic, and stearic acids (P < 0.0001). Vegans had higher linoleic acid (18:2ω-6) relative to non-vegetarians (23.3% compared with 19.1%) (P < 0.0001), and a higher proportion of total ω-3 fatty acids (2.1% compared with 1.6%) (P < 0.0001). Results overall were similar but less robust for lacto-ovo- and pesco-vegetarians. 1-Methylhistidine was 92% lower in vegans, and lower in lacto-ovo- and pesco-vegetarians by 90% and 80%, respectively, relative to non-vegetarians (P < 0.0001). CONCLUSION: AHS-2 participants following vegan, and lacto-ovo- or pesco-vegetarian diet patterns have significant differences in plasma, urine, and adipose tissue biomarkers associated with dietary intakes compared with those who consume a non-vegetarian diet. These findings provide some validation for the prior classification of dietary groups within the AHS-2 cohort.

Comparison of phytosterol intake from FFQ with repeated 24-h dietary recalls of the Adventist Health Study-2 calibration sub-study.

We evaluated the performance of an FFQ in estimating phytosterol intake against multiple 24-h dietary recalls (24HDR) using data from 1011 participants of the calibration sub-study of the Adventist Health Study-2 (AHS-2) cohort. Dietary assessments of phytosterol intake included a self-administered FFQ and six 24HDR and plasma sterols. Plasma sterols were determined using the GLC flame ionisation method. Validation of energy-adjusted phytosterol intake from the FFQ with 24HDR was conducted by calculating crude, unadjusted, partial and de-attenuated correlation coefficients (r) and cross-classification by race. On average, total phytosterol intake from the FFQ was 439·6 mg/d in blacks and 417·9 mg/d in whites. From the 24HDR, these were 295·6 mg/d in blacks and 351·4 mg/d in whites. Intake estimates of ß-sitosterol, stigmasterol, other plant sterols and total phytosterols from the FFQ had moderate to strong correlations with estimates from 24HDR (r 0·41-0·73). Correlations were slightly higher in whites (r 0·42-0·73) than in blacks (r 0·41-0·67). FFQ estimates were poorly correlated with plasma sterols as well as 24HDR v. plasma sterols. We conclude that the AHS-2 FFQ provided reasonable estimates of phytosterol intake and may be used in future studies relating phytosterol intake and disease outcomes.

Meal Frequency and Timing Are Associated with Changes in Body Mass Index in Adventist Health Study 2.

Background: Scientific evidence for the optimal number, timing, and size of meals is lacking.Objective: We investigated the relation between meal frequency and timing and changes in body mass index (BMI) in the Adventist Health Study 2 (AHS-2), a relatively healthy North American cohort.Methods: The analysis used data from 50,660 adult members aged ≥30 y of Seventh-day Adventist churches in the United States and Canada (mean ± SD follow-up: 7.42 ± 1.23 y). The number of meals per day, length of overnight fast, consumption of breakfast, and timing of the largest meal were exposure variables. The primary outcome was change in BMI per year. Linear regression analyses (stratified on baseline BMI) were adjusted for important demographic and lifestyle factors.Results: Subjects who ate 1 or 2 meals/d had a reduction in BMI per year (in kg · m-2 · y-1) (-0.035; 95% CI: -0.065, -0.004 and -0.029; 95% CI: -0.041, -0.017, respectively) compared with those who ate 3 meals/d. On the other hand, eating >3 meals/d (snacking) was associated with a relative increase in BMI (P < 0.001). Correspondingly, the BMI of subjects who had a long overnight fast (≥18 h) decreased compared with those who had a medium overnight fast (12-17 h) (P < 0.001). Breakfast eaters (-0.029; 95% CI: -0.047, -0.012; P < 0.001) experienced a decreased BMI compared with breakfast skippers. Relative to subjects who ate their largest meal at dinner, those who consumed breakfast as the largest meal experienced a significant decrease in BMI (-0.038; 95% CI: -0.048, -0.028), and those who consumed a big lunch experienced a smaller but still significant decrease in BMI than did those who ate their largest meal at dinner.Conclusions: Our results suggest that in relatively healthy adults, eating less frequently, no snacking, consuming breakfast, and eating the largest meal in the morning may be effective methods for preventing long-term weight gain. Eating breakfast and lunch 5-6 h apart and making the overnight fast last 18-19 h may be a useful practical strategy.