Search

Purpose: The roles of folate and vitamin B12 in prostate cancer (PCa) or breast cancer (BC) development are unclear. We investigated their roles using the prospective Swedish Apolipoprotein MOrtality RISk (AMORIS) study.Methods: 8,783 men and 19,775 women with vitamin B12 and folate serum measurements were included. Their associations with PCa and BC risk categories were evaluated using Cox proportional hazards regression.Results: During mean follow-up of 13 years, 703 men developed PCa. There was an inverse association between folate > 32 nmol/L and high-risk PCa [hazard ratio (HR) 0.12, 95% confidence interval (CI) 0.02-0.90], and a positive association between folate < 5 nmol/L and metastatic PCa (HR 5.25, 95% CI 1.29-21.41), compared with folate 5-32 nmol/L. No associations with vitamin B12 were found. 795 women developed BC during mean follow-up of 14 years. When restricting to the fasting population, there was a positive association between folate > 32 nmol/L and BC (HR 1.47, 95% CI 1.06-2.04).Conclusion: High folate levels may protect against PCa and low folate levels may increase risk of metastatic PCa. High fasting folate levels may be associated with an increased BC risk. Vitamin B12 was not found to be linked with risk of PCa or BC. Longitudinal studies with serum and dietary information could help define new prevention targets and add information on the role of folate fortification. [ABSTRACT FROM AUTHOR]

Objective: To assess the associations of blood biomarkers of carbohydrate, lipid, and apolipoprotein metabolisms with the future risk of amyotrophic lateral sclerosis (ALS).Methods: In the Apolipoprotein-related MOrtality RISk study, we enrolled 636,132 men and women during 1985-1996 in Stockholm, Sweden, with measurements of serum glucose, total cholesterol, triglycerides, apolipoprotein B (apoB), and apolipoprotein A-I (apoA-I). Serum low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were either directly measured or calculated from total cholesterol, triglycerides, and apoA-I. The cohort was followed until the end of 2011. We used Cox models and mixed-effects models to, first, estimate the associations between these biomarkers and ALS incidence and, second, to assess the changes of these biomarkers during the 20 years before ALS diagnosis.Results: One-unit increase of LDL-C (hazard ratio [HR] = 1.14; 95% confidence interval [CI] = 1.02-1.27), apoB (HR = 1.68; 95% CI = 1.17-2.42), and apoB/apoA-I ratio (HR = 1.90; 95% CI = 1.29-2.78) was associated with a higher incidence of ALS. High glucose level (≥6.11mmol/L) was associated with a lower incidence (HR = 0.62; 95% CI = 0.42-0.93), whereas high LDL-C/HDL-C (≥3.50; HR = 1.50; 95% CI = 1.15-1.96) and high apoB/apoA-I (≥0.90 for men, ≥0.8 for women; HR = 1.41; 95% CI = 1.04-1.90) ratios were associated with a higher incidence. During the 10 years before diagnosis, ALS patients had increasing levels of LDL-C, HDL-C, apoB, and apoA-I, whereas gradually decreasing levels of LDL-C/HDL-C and apoB/apoA-I ratios.Interpretation: Alterations in the carbohydrate, lipid, and apolipoprotein metabolisms are associated with ALS risk and may serve as prodromal symptoms decades before ALS diagnosis. The imbalance between apoB and apoA-I as well as between LDL-C and HDL-C may be an etiological mechanism for ALS and needs to be further studied. Ann Neurol 2017;81:718-728. [ABSTRACT FROM AUTHOR]

To investigate the association between serum calcium and risk of breast cancer using a large cohort and a systematic review with meta-analysis. From the Swedish Apolipoprotein Mortality Risk (AMORIS) Study we included 229,674 women who had baseline measurements of serum total calcium and albumin. Multivariable Cox regression was used to assess the association between total and albumin-corrected calcium and breast cancer risk. For the systematic review, an electronic search of MEDLINE and EMBASE databases was performed to identify other prospective cohorts assessing the relationship between serum calcium and breast cancer risk. We pooled the results of our AMORIS cohort with other eligible studies in a meta-analysis using a random effects model. I2 test was used to assess heterogeneity. In the AMORIS study, 10,863 women were diagnosed with breast cancer (mean follow-up: 19 years). We found an inverse association between total serum calcium and breast cancer when comparing the fourth quartile to the first quartile (HR: 0.94, 95% CI: 0.88-0.99, p value for trend 0.04) and similar results using albumin-corrected calcium. In the systematic review, we identified another two prospective cohorts evaluating pre-diagnostic serum total calcium and breast cancer. Combining these studies and our findings in AMORIS in a meta-analysis showed a protective effect of serum calcium against breast cancer, with a summary RR of 0.80 (95% CI: 0.66-0.97). No substantial heterogeneity was observed. Our findings in AMORIS and the meta-analysis support an inverse association between serum calcium and breast cancer risk, which warrants mechanistic investigations. [ABSTRACT FROM AUTHOR]

Background: Improvements in detection and treatment of prostate cancer (PCa) translate into more men living with PCa, who are therefore potentially at risk of a secondly diagnosed primary tumour (SDPTs). Little is known about potential biochemical mechanisms linking PCa with the occurrence of SDPTs. The current study aims to investigate serum biomarkers of glucose and lipid metabolism and gamma-glutamyl transferase (GGT) measured prior to PCa diagnosis and their association with the occurrence of SDPTS.Methods: From the Swedish AMORIS cohort, we selected all men diagnosed with PCa between 1996 and 2011, with at least one of the five biomarkers of interest (glucose, fructosamine, triglycerides, total cholesterol (TC), GGT) measured on average 16 years before PCa diagnosis (n = 10,791). Multivariate Cox proportional hazards models were used to determine hazard ratios (HR) for risk of SDPTs (overall and subtypes) by levels of the five biomarkers. Effect modification of treatment was assessed.Results: 811 SDPTS were diagnosed during a median follow-up time of 5 years. Elevated levels of triglycerides (HR: 1.37, 95%CI: 1.17-1.60), TC (HR: 1.22, 95%CI: 1.04-1.42) and GGT (HR: 1.32, 95%CI: 1.02-1.71) were associated with an increased risk of SDPTs. Risk of SDPTs subtypes varied by biomarkers.Conclusion: Elevated levels of biomarkers of lipid metabolism and GGT measured prior to PCa diagnosis were associated with an increased risk of SDPTs, suggesting a potential common biochemical background for development of PCa and SDPTs. [ABSTRACT FROM AUTHOR]

Background: Lipoproteins are associated with acquired aortic valve stenosis (AS). This study investigated whether an elevated apolipoprotein (apo)B/apoA-1 ratio was associated with an increased risk of AS and if this association was influenced by a history of a major adverse cardiovascular event (MACE) defined as stroke, myocardial infarction or revascularisation.Methods: A study was undertaken of 131,816 individuals, aged ≥30 years, from the Swedish Apolipoprotein MOrtality RISk (AMORIS) cohort, with measurements of apolipoproteins B and A-1 at health examinations during 1985-1996.Results: There were fewer women and the average age was 4 years older in the highest apoB/apoA-1 quintile compared with the lowest. Being overweight, having reduced renal function and diabetes mellitus were more frequent. Low-density lipoprotein cholesterol, triglyceride and apolipoprotein B levels were higher in the top apoB/apoA-1 quintile. During follow-up through 2011, non-rheumatic aortic valve disease was diagnosed in 2,999 individuals (2.3%). Using ICD-10 codes from 1997, AS was identified in 1,887 patients. An elevated apoB/apoA-1 ratio was associated with an increased incidence of aortic valve disease after multivariable adjustment [hazard ratio (HR) (95% CI) for the fifth vs first quintile of 1.28 (1.09-1.50)]. Restricting the analyses to incident AS during 1997-2011 yielded an HR of 1.41 (1.15-1.72). This increased incidence was primarily seen in women and individuals aged ≥65 years. History of MACE did not influence these associations.Conclusions: An elevated apoB/apoA-1 ratio was associated with an increased incidence of AS, particularly in women and individuals aged ≥65 years, regardless of previous MACE. [ABSTRACT FROM AUTHOR]