Regular Glucosamine Use May Have Different Roles in the Risk of Site-Specific Cancers: Findings from a Large Prospective Cohort.

BACKGROUND: Previous studies indicated that glucosamine supplements may have a general anticancer effect. This study aimed to assess whether the potential effect differs across different types of cancers in a large prospective cohort study. METHODS: All participants from the UK Biobank who were free of cancers and had complete information on glucosamine use at baseline were included and followed up from 2006 until 2021. Cox proportional hazards models were used to assess the associations between regular glucosamine use and different site-specific cancers. Subgroup analyses were performed to explore potential interactions. Several sensitivity analyses were conducted to assess the robustness of the main findings. RESULTS: A total of 450,207 eligible participants (mean age: 56.2 years; females: 53.3%) were included, of whom 84,895 (18.9%) reported regular glucosamine use at baseline. During a median of 12.5 years follow-up, glucosamine use was significantly associated with an increased risk of overall cancer [HR, 1.04; 95% confidence interval (CI), 1.01-1.06], skin cancer (HR, 1.11; 95% CI, 1.07-1.15), and prostate cancer (HR, 1.07; 95% CI, 1.01-1.13), and with a reduced risk of lung cancer (HR, 0.88; 95% CI, 0.79-0.97) after adjusting for potential confounders. Statistical interaction was observed for gender, age, and education for the association of glucosamine use with overall cancer risk (all Pinteraction < 0.027). These results remained unchanged in the sensitivity analyses. CONCLUSIONS: Regular glucosamine use was associated with lower risk of lung cancer but higher risk of skin cancer, prostate cancer, and overall cancer. IMPACT: The roles of glucosamine use potentially differ in the development of different site-specific cancers.

Plasma selenium and the risk of first stroke in adults with hypertension: a secondary analysis of the China Stroke Primary Prevention Trial.

BACKGROUND: Previous studies have indicated that selenium (Se) may play an important role in cardio-cerebrovascular disease. However, the relation between circulating selenium and risk of first stroke remains inconclusive. OBJECTIVES: We conducted a secondary analysis of the China Stroke Primary Prevention Trial (CSPPT), using a nested case-control design, and aimed to investigate the correlation between Se concentration and first stroke risk in adults with hypertension and examine the potential effect modifiers. METHODS: In the CSPPT, a total of 20,702 adults with hypertension were randomly assigned to a double-blind daily treatment with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. A total of 618 first stroke cases and 618 controls matched for age, sex, treatment group, and study site were included in this study. RESULTS: During a median follow-up duration of 4.5 y (IQR: 4.2-4.6 y), there was a significant inverse association between plasma Se and the risk of first stroke (per SD increment; adjusted OR: 0.81; 95% CI: 0.68, 0.96) and ischemic stroke (per SD increment; adjusted OR: 0.76; 95% CI: 0.62, 0.93). Furthermore, a stronger inverse association between plasma Se and first stroke was observed in participants with higher folate concentrations at baseline [≥7.7 ng/mL (median), adjusted OR: 0.67; 95% CI: 0.54, 0.85, compared with <7.7 ng/mL, adjusted OR: 0.98; 95% CI: 0.80, 1.21; P-interaction = 0.008] and those with higher time-averaged systolic blood pressure (SBP) over the treatment period (≥140 mm Hg, adjusted OR: 0.71; 95% CI: 0.58, 0.86, compared with <140 mm Hg, adjusted OR: 0.96; 95% CI: 0.77, 1.20; P-interaction = 0.023). CONCLUSIONS: There was a significant inverse association between plasma Se and risk of first stroke in Chinese adults with hypertension, especially among those with higher baseline folate concentrations and those with higher time-averaged SBP over the treatment period. This trial was registered at clinicaltrials.gov as NCT00794885.

Sex difference in the association between plasma selenium and first stroke: a community-based nested case-control study.

BACKGROUND: To date, there is no clearly defined association between plasma selenium levels and first stroke. We aimed to investigate the association between baseline plasma selenium and first stroke risk in a community-based Chinese population. METHODS: Using a nested case-control study design, a total of 1255 first stroke cases and 1255 matched controls were analyzed. Participant plasma selenium concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS), and the association of plasma selenium with first stroke risk was estimated by conditional logistic regression models. RESULTS: Overall, a non-linear negative association between plasma selenium and first total stroke and first ischemic stroke risks was found in males but not in females. Compared with participants with lower selenium levels (tertile 1-2, < 94.1 ng/mL), participants with higher selenium levels (tertile 3, ≥ 94.1 ng/mL) had significantly lower risks of first total stroke (OR 0.63; 95% CI 0.48, 0.83) and first ischemic stroke (OR 0.61; 95% CI 0.45, 0.83) in males but not in females with first total stroke (OR 0.92; 95% CI 0.69, 1.22) and first ischemic stroke (OR 0.89; 95% CI 0.65, 1.22). Furthermore, a stronger association between plasma selenium and first total stroke was found in males with higher vitamin E levels (≥ 13.5 µg/mL vs. < 13.5 µg/mL P-interaction = 0.007). No significant association was observed between plasma selenium and first hemorrhagic stroke risk in either males or females. CONCLUSION: Our study indicated a significant, non-linear, negative association between plasma selenium and first stroke in males but not in females. TRIAL REGISTRATION: ChiCTR1800017274 .

Plasma selenium levels and risk of new-onset diabetes in hypertensive adults.

OBJECTIVE: The association between plasma selenium and new-onset diabetes in hypertensive adults is still unclear. We aimed to evaluate the relationship of baseline plasma selenium with new-onset diabetes and examine possible effect modifiers in a post-hoc analysis of the China Stroke Primary Prevention Trial (CSPPT). METHODS: A total of 2367 hypertensive, non-diabetic patients with plasma selenium measurements at baseline were included. The primary outcome was new-onset diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during the follow-up period, or fasting glucose (FG) ≥126.0 mg/dL at the exit visit. RESULTS: At baseline, higher FG levels were found among participants with plasma selenium in quartile 4 (≥94.8 µg/L) (ß, 1.64 mg/dL; 95%CI: 0.54, 2.73) compared to those in quartiles 1-3. During a median follow-up duration of 4.5 years, new-onset diabetes occurred in 270 (11.4%) participants. Graphic plot showed a positive association between baseline selenium levels and risk of new-onset diabetes. This was further confirmed by adjusted regression analyses; the odds ratios (OR) for new-onset diabetes comparing quartile 4 (≥94.8 µg/L) to quartiles 1-3 was 1.36 (95%CI: 1.01, 1.83). No clear trend was evident across quartiles 1-3. CONCLUSIONS: Our data suggest that high plasma selenium (≥94.8 µg/L) was associated with increased risk of new-onset diabetes in hypertensive patients.

A Nested Case-Control Study on Plasma Vitamin E and Risk of Cancer: Evidence of Effect Modification by Selenium.

BACKGROUND: Evidence from epidemiologic studies has been inconsistent regarding the role of vitamin E in cancer incidence risk. OBJECTIVE: The aim of this study was to evaluate the prospective association between baseline plasma vitamin E levels and subsequent cancer risk in Chinese adults with hypertension, and to identify effect modifiers. DESIGN: A nested, case-control study was conducted from 20,702 hypertensive participants in the China Stroke Primary Prevention Trial, a randomized, double-blind, controlled trial, conducted from May 2008 to August 2013. PARTICIPANTS: The current study included 229 new cancer cases and 229 controls matched for age (±1 year), sex, treatment group, and study site. MAIN OUTCOME MEASURES: Plasma vitamin E was measured by liquid chromatography with tandem quadrupole mass spectrometers and plasma selenium was measured by inductively coupled plasma mass spectrometry using Thermo Fisher iCAP Q ICP-MS. STATISTICAL ANALYSES: Odds ratios (OR) of cancer in relation to plasma concentrations of vitamin E were calculated using conditional logistic regression models. RESULTS: Median follow-up duration was 4.5 years. Overall, vitamin E was not associated with subsequent risk of total cancer (per 1-mg/L [2.3 µmol/L] increase: OR 1.01, 95% CI 0.93 to 1.09) and non-gastrointestinal cancer (OR 1.10, 95% CI 0.98 to 1.24). However, there was a significant, inverse association between vitamin E and gastrointestinal cancer (OR 0.86, 95% CI 0.75 to 0.99), particularly esophageal cancer (OR 0.67, 95% CI 0.48 to 0.95). Moreover, high vitamin E decreased the risk of total cancer (OR 0.91, 95% CI 0.84 to 0.99) and gastrointestinal cancer (OR 0.83, 95% CI 0.73 to 0.95) among patients with high selenium levels (median≥83.7 µg/L [1.1 µmol/L]), and increased the risk of total cancer (OR 1.13, 95% CI 1.00 to 1.26) and non-gastrointestinal cancer (OR 1.25, 95% CI 1.03 to 1.50) among those with low selenium levels (<83.7 µg/L [1.1 µmol/L]). CONCLUSIONS: This study suggests that higher levels of plasma vitamin E are associated with reduced risk of gastrointestinal cancer. High vitamin E decreased the risk of total cancer among patients with high selenium levels, but increased the risk of total cancer among those with low selenium levels.