How retinol as a clinical indicator of vitamin A status is related to long-term mortality is unknown. Here we report the results of a prospective analysis examining associations between serum retinol ...and risk of overall and cause-specific mortality. During a 30-year cohort follow-up, 23,797 deaths were identified among 29,104 men. Participants with higher serum retinol experienced significantly lower overall, CVD, heart disease, and respiratory disease mortality compared to men with the lowest retinol concentrations, reflecting 17-32% lower mortality risk (P
< 0.0001). The retinol-overall mortality association is similar across subgroups of smoking intensity, alcohol consumption, body mass index, trial supplementation, serum alpha-tocopherol and beta-carotene concentrations, and follow-up time. Mediation analysis indicated that <3% of the effects of smoking duration and diabetes mellitus on mortality were mediated through retinol concentration. These findings indicate higher serum retinol is associated with lower overall mortality, including death from cardiovascular, heart, and respiratory diseases.
Although insulin may increase the risk of some cancers, few studies have examined fasting serum insulin and lung cancer risk.
We examined serum insulin, glucose, and indices of insulin resistance ...insulin:glucose molar ratio and homeostasis model assessment of insulin resistance (HOMA-IR) and lung cancer risk using a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish men. A total of 196 cases and 395 subcohort members were included. Insulin and glucose were measured in fasting serum collected 5 to 12 years before diagnosis. Cox proportional hazards models were utilized to estimate the relative risk of lung cancer.
The average time between blood collection and lung cancer was 9.6 years. Fasting serum insulin levels were 8.7% higher in subcohort members than cases. After multivariable adjustment, men in the fourth quartile of insulin had a significantly higher risk of lung cancer than those in the first quartile HR = 2.10; 95% confidence interval (CI), 1.12-3.94. A similar relationship was seen with HOMA-IR (HR = 1.83; 95% CI, 0.99-3.38). Risk was not strongly associated with glucose or the insulin:glucose molar ratio (
= 0.55 and
= 0.27, respectively).
Higher fasting serum insulin concentrations, as well as the presence of insulin resistance, appear to be associated with an elevated risk of lung cancer development.
Although insulin is hypothesized to increase risk of some cancers, insulin and lung cancer remain understudied. Higher insulin levels and insulin resistance were associated with increased lung cancer risk. Although smoking cessation is the best method of lung cancer prevention, other lifestyle changes that affect insulin concentrations and sensitivity may reduce lung cancer risk.
.
Purpose
To determine whether higher coffee intake may reduce the risk of renal cell cancer (RCC) associated with lead (Pb) and other heavy metals with known renal toxicity. Methods: We conducted a ...nested case–control study of male smokers (136 RCC cases and 304 controls) within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Cases diagnosed with RCC at 5 or more years following cohort enrollment were matched to controls on age (± 7 years) and whole blood draw date (± 30 days). Conditional logistic regression (using two-sided tests) was used to test for main effects and additive models of effect modification. Results: After a mean follow-up of 16.3 years, coffee consumption was not significantly associated with renal cell cancer risk, when adjusting for blood concentrations of Cd, Hg, and Pb and RCC risk factors (age, smoking, BMI, and systolic blood pressure) (p-trend, 0.134). The association with above median blood Pb and RCC (HR = 1.69, 95% CI 1.06, 2.85) appeared to be modified by coffee consumption, such that RCC risk among individuals with both increased coffee intake and higher blood lead concentration were more than threefold higher RCC risk (HR = 3.40, 95% CI 1.62, 7.13; p-trend, 0.003). Conclusion: Contrary to our initial hypothesis, this study suggests that heavy coffee consumption may increase the previously identified association between higher circulating lead (Pb) concentrations and increased RCC risk. Improved assessment of exposure, including potential trace element contaminants in coffee, is needed.
Trimethylamine N-oxide (TMAO), a choline-derived metabolite produced by gut microbiota, and its biomarker precursors have not been adequately evaluated in relation to colorectal cancer risk.
We ...investigated the relationship between serum concentrations of TMAO and its biomarker precursors (choline, carnitine, and betaine) and incident colorectal cancer risk in a nested case-control study of male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. We measured biomarker concentrations in baseline fasting serum samples from 644 incident colorectal cancer cases and 644 controls using LC/MS-MS. Logistic regression models estimated the ORs and 95% confidence interval (CI) for colorectal cancer by quartile (Q) of serum TMAO, choline, carnitine, and betaine concentrations.
Men with higher serum choline at ATBC baseline had approximately 3-fold greater risk of developing colorectal cancer over the ensuing (median ± IQR) 14 ± 10 years (in fully adjusted models, Q4 vs. Q1, OR, 3.22; 95% CI, 2.24-4.61;
< 0.0001). The prognostic value of serum choline for prediction of incident colorectal cancer was similarly robust for proximal, distal, and rectal colon cancers (all
< 0.0001). The association between serum TMAO, carnitine, or betaine and colorectal cancer risk was not statistically significant (
= 0.25, 0.71, and 0.61, respectively).
Higher serum choline concentration (but not TMAO, carnitine, or betaine) was associated with increased risk of colorectal cancer.
Serum choline levels showed strong prognostic value for prediction of incident colorectal cancer risk across all anatomical subsites, suggesting a role of altered choline metabolism in colorectal cancer pathogenesis.
.
The primary circulating form of vitamin D, 25-hydroxy-vitamin D 25(OH)D, is associated with multiple medical outcomes, including rickets, osteoporosis, multiple sclerosis and cancer. In a genome-wide ...association study (GWAS) of 4501 persons of European ancestry drawn from five cohorts, we identified single-nucleotide polymorphisms (SNPs) in the gene encoding group-specific component (vitamin D binding) protein, GC, on chromosome 4q12-13 that were associated with 25(OH)D concentrations: rs2282679 (P = 2.0 × 10−30), in linkage disequilibrium (LD) with rs7041, a non-synonymous SNP (D432E; P = 4.1 × 10−22) and rs1155563 (P = 3.8 × 10−25). Suggestive signals for association with 25(OH)D were also observed for SNPs in or near three other genes involved in vitamin D synthesis or activation: rs3829251 on chromosome 11q13.4 in NADSYN1 encoding nicotinamide adenine dinucleotide (NAD) synthetase; P = 8.8 × 10−7, which was in high LD with rs1790349, located in DHCR7, the gene encoding 7-dehydrocholesterol reductase that synthesizes cholesterol from 7-dehydrocholesterol; rs6599638 in the region harboring the open-reading frame 88 (C10orf88) on chromosome 10q26.13 in the vicinity of ACADSB (acyl-Coenzyme A dehydrogenase), involved in cholesterol and vitamin D synthesis (P = 3.3 × 10−7); and rs2060793 on chromosome 11p15.2 in CYP2R1 (cytochrome P450, family 2, subfamily R, polypeptide 1, encoding a key C-25 hydroxylase that converts vitamin D3 to an active vitamin D receptor ligand; P = 1.4 × 10−5). We genotyped SNPs in these four regions in 2221 additional samples and confirmed strong genome-wide significant associations with 25(OH)D through meta-analysis with the GWAS data for GC (P = 1.8 × 10−49), NADSYN1/DHCR7 (P = 3.4 × 10−9) and CYP2R1 (P = 2.9 × 10−17), but not C10orf88 (P = 2.4 × 10−5).
Using data from the National Institutes of Health-AARP Diet and Health Study, we evaluated the influence of adulthood weight history on mortality risk. The National Institutes of Health-AARP Diet and ...Health Study is an observational cohort study of US men and women who were aged 50-71 years at entry in 1995-1996. This analysis focused on 109,947 subjects who had never smoked and were younger than age 70 years. We estimated hazard ratios of total and cause-specific mortality for recalled body mass index (BMI; weight (kg)/height (m)(2)) at ages 18, 35, and 50 years; weight change across 3 adult age intervals; and the effect of first attaining an elevated BMI at 4 successive ages. During 12.5 years' follow-up through 2009, 12,017 deaths occurred. BMI at all ages was positively related to mortality. Weight gain was positively related to mortality, with stronger associations for gain between ages 18 and 35 years and ages 35 and 50 years than between ages 50 and 69 years. Mortality risks were higher in persons who attained or exceeded a BMI of 25.0 at a younger age than in persons who reached that threshold later in adulthood, and risks were lowest in persons who maintained a BMI below 25.0. Heavier initial BMI and weight gain in early to middle adulthood strongly predicted mortality risk in persons aged 50-69 years.
Background
Family history may inform risks of gastric cancer and preneoplastic lesions.
Methods
We examined associations with history of cancer in first-degree relatives for 307 incident gastric ...cancer cases among 20,720 male smokers in a prospective study in Finland. Cox regression was used to calculate gastric cancer hazard ratios (HR) and 95% confidence intervals (95% CI). Logistic regression was used to estimate odds ratios (OR) and 95% CIs for low serum pepsinogen, a marker of gastric atrophy.
Results
Gastric cancer risk was associated with gastric cancer history in first-degree relatives overall (HR 1.56, 95% CI 1.15–2.12), in fathers (HR 1.67, 95% CI 1.09–2.55) and in siblings (HR 2.05, 95% CI 1.25–3.38). Associations were significant for noncardia (HR 1.83, 95% CI 1.30–2.57) but not cardia (HR 0.93, 95% CI 0.46–1.87) cancers, and marginal for both intestinal—(HR 1.53, 95% CI 0.92–2.55) and diffuse-type (HR 1.47, 95% CI 0.72–3.03) histologies. Family history of other cancer types was not associated with gastric cancer risk. Family history of gastric cancer was associated with low pepsinogen (OR 1.29, 95% CI 1.11–1.50).
Conclusions
Family history of gastric cancer is strongly associated with specific subtypes of gastric cancer as well as with gastric atrophy, a risk factor for developing this malignancy.
Background
Obesity has been positively associated with gastric cancer. Excess fat impacts hormones, which have been implicated in carcinogenesis. We investigated obesity-related hormones and cardia ...gastric cancer (CGC) and non-cardia gastric cancer (NCGC) risk.
Methods
Nested case–control studies were conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (61 CGCs, and 172 NCGCs and matched controls) and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study (100 CGCs and 65 NCGCs and matched controls); serum hormones were measured. In UK-Biobank (
n
= 458,713), we included 137 CGCs and 92 NCGCs. Sex-specific analyses were conducted. For EPIC and ATBC, odds ratios (ORs), and for UK-Biobank hazard ratios (HRs), were estimated using conditional logistic regression and Cox regression, respectively.
Results
Insulin-like growth-factor-1 was positively associated with CGC and NCGC in EPIC men (OR
per 1-SD increase
1.94, 95% CI 1.03–3.63; OR
per 1-SD increase
1.63, 95% CI 1.05–2.53, respectively), with similar findings for CGC in UK-Biobank women (HR
per 1-SD increase
1.76, 95% CI 1.08–2.88). Leptin in EPIC men and C-peptide in EPIC women were positively associated with NCGC (OR
T3 vs. T1
2.72, 95% CI 1.01–7.34 and OR
per 1-SD increase
2.17, 95% CI 1.19–3.97, respectively). Sex hormone-binding globulin was positively associated with CGC in UK-Biobank men (HR
per 1-SD increase
1.29, 95% CI 1.02–1.64). Conversely, ghrelin was inversely associated with NCGC among EPIC and ATBC men (OR
per 1-SD increase
0.53, 95% CI 0.34–0.84; OR
per 1-SD increase
0.22, 95% CI 0.10–0.50, respectively). In addition, dehydroepiandrosterone was inversely associated with CGC in EPIC and ATBC men combined.
Conclusions
Some obesity-related hormones influence CGC and NCGC risk.
The International Agency for Research on Cancer reported that some chemicals in hair dyes are probably carcinogenic to those exposed to them occupationally. Biological mechanisms through which hair ...dye use may be related to human metabolism and cancer risk are not well-established. We conducted the first serum metabolomic examination comparing hair dye users and nonusers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Metabolite assays were conducted using ultrahigh performance liquid chromatography-tandem mass spectrometry. The association between metabolite levels and hair dye use was estimated using linear regression, adjusting for age, body mass index, smoking, and multiple comparisons. Among the 1,401 detected metabolites, 11 compounds differed significantly between the two groups, including four amino acids and three xenobiotics. Redox-related glutathione metabolism was heavily represented, with L-cysteinylglycine disulfide showing the strongest association with hair dye (effect size (β) = - 0.263; FDR adjusted p-value = 0.0311), along with cysteineglutathione disulfide (β = - 0.685; FDR adjusted p-value = 0.0312). 5alpha-Androstan-3alpha,17beta-diol disulfate was reduced in hair dye users (β = - 0.492; FDR adjusted p-value = 0.077). Several compounds related to antioxidation/ROS and other pathways differed significantly between hair dye users and nonusers, including metabolites previously associated with prostate cancer. Our findings suggest possible biological mechanisms through which the use of hair dye could be associated with human metabolism and cancer risk.
PDF
