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Background A growing body of literature suggests chronically higher bile acid (BA) concentrations may be associated with multiple health conditions. Diet may affect BA metabolism and signaling; however, evidence from human populations is lacking. Objectives We systematically investigated cross-sectional associations of a priori–selected dietary components (fiber, alcohol, coffee, fat) with circulating BA concentrations. Methods We used targeted, quantitative LC-MS/MS panels to measure 15 circulating BAs in a subset of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC; n  = 2224) and Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO; n  = 986) comprising Finnish male smokers and United States men and women, respectively. We used multivariable linear regression to estimate associations of each dietary component with log-transformed BAs; exponentiated coefficients estimate proportional differences. We included the median of the dietary component quartile in linear regression models to test for trend. Results In ATBC, fiber was inversely associated with multiple circulating BAs. The proportional difference was –10.09% (95% CI: −19.29 to 0.16; P- trend = 0.04) when comparing total BAs among those in the highest relative to the lowest fiber quartile. Alcohol, trans fat, and polyunsaturated fat were positively associated with BAs in ATBC. The proportional difference comparing total BAs among those in the highest relative to the lowest alcohol quartile was 8.76% (95% CI: –3.10 to 22.06; P- trend = 0.03). Coffee and monounsaturated fat were inversely associated with BAs. The proportional difference comparing total BAs among those in the highest relative to the lowest coffee quartile was –24.03% (95% CI: –31.57 to –15.66; P- trend < 0.0001). In PLCO, no dietary components were associated with BAs except fiber, which was inversely associated with tauroursodeoxycholic acid. Conclusions Alcohol, coffee, certain fat subtypes, and fiber were associated with circulating concentrations of multiple BAs among Finnish male smokers. Given the potential role of BAs in disease risk, further investigation of the effects of diet on BAs in humans is warranted. [ABSTRACT FROM AUTHOR]

Background: Coffee has been consistently associated with lower risk of liver cancer and chronic liver disease, suggesting that coffee affects mechanisms underlying disease development.Methods: We measured serum metabolites using untargeted metabolomics in 1:1 matched nested case-control studies of liver cancer (n = 221 cases) and fatal liver disease (n = 242 cases) in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention cohort (n = 29 133). Associations between baseline coffee drinking and metabolites were identified using linear regression; conditional logistic regression models were used to identify associations with subsequent outcomes.Results: Overall, 21 metabolites were associated with coffee drinking and also each subsequent endpoint; nine metabolites and trigonelline, a known coffee biomarker, were identified. Tyrosine and two bile acids, glycochenodeoxycholic acid (GCDCA) and glycocholic acid (GCA), were inversely associated with coffee but positively associated with both outcomes; odds ratios (ORs) comparing the 90th to 10th percentile (modeled on a continuous basis) ranged from 3.93 (95% confidence interval [CI] = 2.00 to 7.74) for tyrosine to 4.95 (95% CI = 2.64 to 9.29) for GCA and from 4.00 (95% CI = 2.42 to 6.62) for GCA to 6.77 (95% CI = 3.62 to 12.65) for GCDCA for liver cancer and fatal liver disease, respectively. The remaining six metabolites and trigonelline were positively associated with coffee drinking but inversely associated with both outcomes; odds ratio ranged from 0.16 to 0.37. Associations persisted following diet adjustment and for outcomes occurring greater than 10 years after blood collection.Conclusions: A broad range of compounds were associated with coffee drinking, incident liver cancer, and liver disease death over 27 years of follow-up. These associations provide novel insight into chronic liver disease and liver cancer etiology and support a possible hepatoprotective effect of coffee. [ABSTRACT FROM AUTHOR]

Background: The nonessential amino acid cysteine is known to be involved in many antioxidant and anticarcinogenic pathways. Cysteinylglycine is a pro-oxidant metabolite of glutathione and a precursor of cysteine. Objective: To examine the relation between serum cysteine and cysteinylglycine and risk of gastric adenocarcinomas, esophageal squamous cell carcinomas, and head and neck squamous cell carcinomas, we conducted a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention study of male Finnish smokers aged 50-69 y at baseline. Design: In total, 170 gastric adenocarcinomas, 68 esophageal squamous cell carcinomas, and 270 head and neck squamous cell carcinomas (identified from the Finnish Cancer Registry) were matched one-to-one with cancer-free control subjects on age and the date of serum collection. We calculated ORs and 95% CIs with the use of a multivariate-adjusted conditional logistic regression. Results: Cysteine had a U-shaped association with gastric adenocarcinomas; a model that included a linear and a squared term had a significant global P-test (P = 0.036). Serum cysteinylglycine was inversely associated with adenocarcinomas of the gastric cardia (OR for above the median compared with below the median: 0.07; 95% CI: 0.01, 0.70; n = 38 cases) but not for other sites. Both cysteine and cysteinylglycine were not associated with esophageal squamous cell carcinoma or head and neck squamous cell carcinoma. Conclusions: We observed associations between serum cysteine and cysteinylglycine with upper gastrointestinal cancer risk. Future studies are needed to replicate these findings. This trial was registered at clininicaltrials.gov as NCT00342992. [ABSTRACT FROM AUTHOR]

Background: Reducing cigarettes per day may lower the risk of lung cancer compared with continuing to smoke at the same intensity. Other changes in smoking behaviors, such as increasing cigarette consumption or quitting for a period and relapsing, may also affect lung cancer risk., Methods: We examined changes in smoking status and cigarettes per day among 24 613 Finnish male smokers aged 50-69 years who participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Longitudinal data on smoking were collected during study follow-up visits 3 times a year (approximately every 4 months) between 1985 and 1993. Incident lung cancer patients through 2012 were identified by the Finnish Cancer Registry. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression., Results: Compared with smoking 20 cigarettes per day continuously across the intervention period, reducing an average of 5 cigarettes per day per year while smoking was associated with a 20% lower risk of lung cancer (95% CI = 0.71 to 0.90). A substantially lower risk of lung cancer was also observed when participants smoked at 50% (RR = 0.72, 95% CI = 0.57 to 0.90) and 10% (RR = 0.55, 95% CI = 0.36 to 0.83) of study visits, relative to smoked at 100% of study visits., Conclusions: Smokers may lower their risk of lung cancer by reducing smoking intensity (cigarettes per day while smoking) and the time they smoke. However, quitting smoking completely is the most effective way for smokers to reduce their risk of lung cancer., (Published by Oxford University Press 2024.)

Background: Coffee has been consistently associated with lower risk of liver cancer and chronic liver disease, suggesting that coffee affects mechanisms underlying disease development., Methods: We measured serum metabolites using untargeted metabolomics in 1:1 matched nested case-control studies of liver cancer (n = 221 cases) and fatal liver disease (n = 242 cases) in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention cohort (n = 29 133). Associations between baseline coffee drinking and metabolites were identified using linear regression; conditional logistic regression models were used to identify associations with subsequent outcomes., Results: Overall, 21 metabolites were associated with coffee drinking and also each subsequent endpoint; nine metabolites and trigonelline, a known coffee biomarker, were identified. Tyrosine and two bile acids, glycochenodeoxycholic acid (GCDCA) and glycocholic acid (GCA), were inversely associated with coffee but positively associated with both outcomes; odds ratios (ORs) comparing the 90th to 10th percentile (modeled on a continuous basis) ranged from 3.93 (95% confidence interval [CI] = 2.00 to 7.74) for tyrosine to 4.95 (95% CI = 2.64 to 9.29) for GCA and from 4.00 (95% CI = 2.42 to 6.62) for GCA to 6.77 (95% CI = 3.62 to 12.65) for GCDCA for liver cancer and fatal liver disease, respectively. The remaining six metabolites and trigonelline were positively associated with coffee drinking but inversely associated with both outcomes; odds ratio ranged from 0.16 to 0.37. Associations persisted following diet adjustment and for outcomes occurring greater than 10 years after blood collection., Conclusions: A broad range of compounds were associated with coffee drinking, incident liver cancer, and liver disease death over 27 years of follow-up. These associations provide novel insight into chronic liver disease and liver cancer etiology and support a possible hepatoprotective effect of coffee., (Published by Oxford University Press 2019. This work is written by US Government employees and is in the public domain in the US.)

Purpose: We evaluated the association of coffee and tea drinking with risk of the urinary tract cancer in Finnish men, with high coffee consumption, using data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study., Methods: The ATBC trial conducted from 1985 to 1993 enrolled 29,133 male smokers. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and confidence intervals (CIs), using men who drank more than 0 but less than 1 cup coffee/d and tea nondrinkers as our referent group for coffee and tea analyses, respectively., Results: During 472,402 person-years of follow-up, 835 incident cases of bladder cancer and 366 cases of renal cell carcinoma were ascertained. For bladder cancer, we observed no association for coffee consumption (HR ≥4 vs. >0 to <1 cups/d = 1.16, 95% CI = 0.86-1.56) and a borderline statistically significant inverse association for tea consumption (HR ≥1 vs. 0 cup/d = 0.77, 95% CI = 0.58-1.00). For renal cell carcinoma, we observed no association for coffee (HR ≥4 vs. >0 to <1 cups/d = 0.85, 95% CI = 0.55-1.32) or tea consumption (HR ≥1 vs. 0 cup/d = 1.00, 95% CI = 0.68-1.46). We found no impact of coffee preparation on coffee-cancer associations., Conclusions: Coffee drinking was not associated with urinary tract cancers risk. Further research on tea and bladder cancer is warranted., (Published by Elsevier Inc.)

Background: Although circulating 25-hydroxyvitamin D [25(OH)D] concentrations were linked to liver cancer and chronic liver disease (CLD) in laboratory studies, few epidemiologic studies have addressed the associations. Methods: Within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, we measured 25(OH)D in baseline serum of 202 incident liver cancer cases and 225 CLD deaths that occurred during nearly 25 years of follow-up, and 427 controls. ORs and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. We examined predetermined clinically defined cut-points, and season-specific and season-standardized quartiles. Results: Low serum 25(OH)D concentrations were associated with higher risk of liver cancer (<25 nmol/L vs. ≥50 nmol/L: 1.98; 95% CI, 1.22-3.20; P trend across categories = 0.003) and CLD mortality (1.93; 95% CI, 1.23-3.03; P trend = 0.006) in models adjusted for age and date of blood draw. After additional adjustment for body mass index, diabetes, smoking, and other potential confounders, the association remained statistically significant for liver cancer (1.91; 95% CI, 1.16-3.15; P Our results suggest a possible preventive role for vitamin D against liver cancer and CLD, although the importance of the liver for vitamin D metabolism and the lack of information about underlying liver disease makes reverse causality a concern. trend Future studies are needed to evaluate associations of vitamin D with liver cancer and liver disease in other populations, particularly those with a different constellation of risk factors. P trend = 0.05). Associations were similar for analyses using season-specific and season-standardized quartiles, and after excluding participants with diabetes, or hepatitis B or C. Conclusions: Our results suggest a possible preventive role for vitamin D against liver cancer and CLD, although the importance of the liver for vitamin D metabolism and the lack of information about underlying liver disease makes reverse causality a concern. Impact: Future studies are needed to evaluate associations of vitamin D with liver cancer and liver disease in other populations, particularly those with a different constellation of risk factors. Cancer Epidemiol Biomarkers Prev; 27(9); 1075-82. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Previous studies have found associations between one-carbon metabolism nutrients and risk of several cancers, but little is known regarding upper gastrointestinal tract (UGI) cancer. We analyzed prediagnostic serum concentrations of several one-carbon metabolism nutrients (vitamin B12, folate, vitamin B6, riboflavin and homocysteine) in a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of male smokers, which was undertaken in Finland between 1985 and 1988. We conducted a nested case-control study including 127 noncardia gastric adenocarcinoma (NCGA), 41 esophagogastric junctional adenocarcinoma and 60 esophageal squamous cell carcinoma incident cases identified within ATBC. Controls were matched to cases on age, date of serum collection and follow-up time. One-carbon nutrient concentrations were measured in fasting serum samples collected at baseline (up to 17 years prior to cancer diagnosis). Odds ratios and 95% confidence intervals (CI) were calculated using conditional logistic regression. Lower prediagnostic vitamin B12 concentrations at baseline were associated with a 5.8-fold increased risk of NCGA (95% CI = 2.7-12.6 for lowest compared to highest quartile, p-trend <0.001). This association remained in participants who developed cancer more than 10 years after blood collection, and after restricting the analysis to participants with clinically normal serum vitamin B12 (>300 pmol/L). In contrast, pepsinogen I, a known serologic marker of gastric atrophy, was not associated with NCGA in this population. As vitamin B12 absorption requires intact gastric mucosa to produce acid and intrinsic factor, our findings suggest vitamin B12 as a possible serologic marker for the atrophic gastritis that precedes NCGA, one more strongly associated with subsequent NCGA than pepsinogen., (Published 2017. This article is a US Government work and, as such, is in the public domain of the United States of America.)

Background: Gastrin, which induces gastric acid secretion, and a structurally similar hormone, cholecystokinin (CCK)-a potent acid inhibitor, may each play a role in gastric cancer. However, few studies have investigated this hypothesis in humans. We therefore investigated whether serum gastrin or CCK concentrations at baseline were associated with the incidence of gastric non-cardia adenocarcinomas (GNCA), oesophagogastric junctional adenocarcinomas (EGJA) or gastric carcinoid tumours over 24 years of follow-up in a study nested within the all-male Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of Finnish smokers., Methods: Totals of 283 incident GNCA, 96 EGJA and 10 gastric carcinoid cases, and 778 matched controls, were included in our analysis. Gastrin and CCK were measured using specific radioimmunoassays. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by multivariable logistic regression with adjustment for all known or suspected confounding factors, including Helicobacter pylori seropositivity., Results: Those with high gastrin (Q4 vs Q1), had an increased risk of GNCA (fully adjusted OR: 1.92; 95% CI: 1.21, 3.05) and gastric carcinoids, though the small number of carcinoid cases meant the fully adjusted model was unstable (age-adjusted continuous model OR: 4.67; 95% CI: 2.67, 8.15). CCK was associated with risk of GNCA only for those in Q3 relative to Q1 (OR: 0.56; 95% CI: 0.33, 0.96), and no significant trend was observed., Conclusions: Our data suggest that high serum concentrations of gastrin may be associated independently with an increased risk of gastric cancer; the role of CCK in cancer risk is less clear., (Published by Oxford University Press on behalf of the International Epidemiological Association 2017. This work is written by US Government employees and is in the public domain in the United States.)

Background: Cancers of the upper gastrointestinal tract remain a substantial cause of morbidity and mortality worldwide. Ghrelin is a hormone produced in the oxyntic glands of the stomach, and under conditions of chronic inflammation and atrophy, serum ghrelin concentrations decrease. However, the relationship between ghrelin and the risk of gastric and esophagogastric junctional cancers has not been investigated., Methods: We conducted a nested case-control study within the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study to examine the relationship between serum ghrelin concentration and the risk of gastric noncardia adenocarcinoma (GNCA) and esophagogastric junctional adenocarcinoma (EGJA). Data from 261 GNCA patients, 98 EGJA patients, and 441 control subjects were analyzed. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using logistic regression with adjustment for potential confounders. Lag analysis was also performed to investigate the temporal nature of the associations between baseline serum pepsinogen I and ghrelin in GNCA and EGJA patients. All statistical tests were two-sided., Results: Lower concentrations of serum ghrelin were statistically significantly associated with an increased risk of both GNCA (adjusted OR = 1.75, 95% CI = 1.49 to 2.04; P < .001) and EGJA (adjusted OR = 1.56, 95% CI = 1.28 to 1.89, P < .001). A multivariable model found that the risk of both GNCA and EGJA were statistically significantly increased for those individuals in the lowest quartile of serum ghrelin levels compared with those in the highest quartile (OR of GNCA = 5.63, 95% CI = 3.16 to 10.03; OR of EGJA = 4.90, 95% CI = 2.11 to 11.35). The statistical significance of these associations remained even after restricting the analysis to those patients who developed cancer more than 10 years after baseline serum ghrelin measurements., Conclusion: Low baseline concentrations of serum ghrelin were associated with a statistically significant increase in the risk of GNCA and EGJA, suggesting a potential role for gastric hormones in carcinogenesis.