Baseline serum folate, vitamin B12 and the risk of prostate and breast cancer using data from the Swedish AMORIS cohort.

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.

Serum glucose, triglycerides, and cholesterol in relation to prostate cancer death in the Swedish AMORIS study.

PURPOSE: Lifestyle-related conditions such as obesity are associated with prostate cancer progression, but the associations with hyperglycemia and dyslipidemia are unclear. This study, therefore, aims to examine the association of glucose, triglycerides, and total cholesterol with prostate cancer death. METHODS: From the Swedish AMORIS cohort, we selected 14,150 men diagnosed with prostate cancer between 1996 and 2011 who had prediagnostic measurements of serum glucose, triglycerides, and total cholesterol. Multivariable Cox proportional hazards regression models were used to determine the hazard ratios for death in relation to the aforementioned metabolic markers. RESULTS: Using clinical cut-off points, a non-significant positive association was observed between glucose and prostate cancer death. When compared to those with glucose in the lowest quartile, those in the highest quartile had greater risk of prostate cancer death (HR 1.19; 95% CI 1.02-1.39). However, neither total cholesterol nor triglycerides were associated with prostate cancer death. Glucose and triglycerides were positively associated with overall, cardiovascular, and other deaths. Hypercholesterolemia was only associated with risk of CVD death. CONCLUSION: Our results suggest that glucose levels may influence prostate cancer survival, but further studies using repeated measurements are needed to further elucidate how glucose levels may influence prostate cancer progression.

Chronic inflammation markers are associated with risk of pancreatic cancer in the Swedish AMORIS cohort study.

BACKGROUND: Nested case-control studies examining the association between serum markers of chronic inflammation, focused on three specific biomarkers (CRP, IL-8 and TNF-α), and risk of pancreatic cancer have reported no associations. In this study, we evaluated associations between standard pre-diagnostic serum markers of chronic inflammation (CRP, albumin, haptoglobin and leukocytes) and pancreatic cancer risk in the Swedish Apolipoprotein-related MORtality RISk (AMORIS) prospective cohort study. METHODS: We selected all participants (≥20 years old) with baseline measurements of CRP, albumin, haptoglobin and leukocytes between 1985 and 1996 (n = 61,597). Participants were excluded if they had a history of chronic pancreatitis and all individuals were free from pancreatic cancer at baseline. Cox proportional multivariable hazards regression analysis was carried out for medical cut-offs of CRP, albumin, haptoglobin and leukocytes. RESULTS: We observed an increased risk of pancreatic cancer for those individuals with higher levels of serum haptoglobin (≥1.4 g/L), CRP (≥10 mg/L) and leukocytes (≥10 × 109 cells/L) compared to those with haptoglobin levels < 1.4 g/L, CRP levels < 10 mg/L and Leukocyte levels < 10 × 109 cells/L [haptoglobin HR: 2.23 (95% CI 1.72-2.88), CRP HR: 1.32 (95% CI 1.00-1.74), leukocytes HR: 2.20 (95% CI 1.52-3.18)]. No associations were noted for serum albumin. CONCLUSIONS: We found an increased risk of pancreatic cancer associated with pre-diagnostic serum levels of haptoglobin, CRP and leukocytes. Our finding suggests a possible role of chronic inflammation in the aetiology of pancreatic cancer and highlight the need to further investigate this association.

Blood biomarkers of carbohydrate, lipid, and apolipoprotein metabolisms and risk of amyotrophic lateral sclerosis: A more than 20-year follow-up of the Swedish AMORIS cohort.

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.

Can pre-diagnostic serum levels of sodium and potassium predict prostate cancer survival?

There is evidence that derangement in serum electrolytes like sodium and potassium is associated with increased morbidity and mortality among hospitalized critically ill patients, but their role in the context of cancer survival remains poorly understood. We sought to investigate the association of pre-diagnostic serum sodium and potassium with risk of overall, cancer-specific, and cardiovascular (CV) death among 11,492 men diagnosed with prostate cancer (PCa) from the Swedish AMORIS study. Multivariable Cox proportional hazards regression was used to assess the risk of death by clinical categories of pre-diagnostic serum sodium and potassium. During a mean follow-up of 5.7 years, 1649 men died of PCa. Serum levels of sodium were not indicative of PCa-specific or CV death. A weak positive association was found between pre-diagnostic higher serum potassium (> 5 mEq/L) and overall death [HR: 1.26 (95% CI: 1.01-1.59)] as compared to low/normal levels of clinical cut-offs. The current study did not find strong evidence for a role of electrolytes in PCa mortality. To further disentangle the potential role of electrolytes in cancer development, future studies should use repeated measurement of serum electrolytes.This research project was reviewed and approved by the Stockholm Ethical Committee (Dnr 2010/1:7).

Glucose, lipids and gamma-glutamyl transferase measured before prostate cancer diagnosis and secondly diagnosed primary tumours: a prospective study in the Swedish AMORIS cohort.

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.

Elevations of metabolic risk factors 20 years or more before diagnosis of type 2 diabetes: Experience from the AMORIS study.

AIMS: To describe trajectories for metabolic risk factors for type 2 diabetes (T2D) up to 25 years prior to diagnosis and to estimate the absolute 20-year risk for T2D based on a simple set of commonly measured key risk factors. METHODS: From the Swedish AMORIS cohort we included 296 428 individuals with data on fasting glucose obtained in health examinations during 1985-1996 (baseline period). All participants were followed until 2012 for development of incident T2D. The 20-year T2D risk based on age, sex, body mass index (BMI), fasting glucose and triglycerides was estimated. Trajectories for biomedical risk factors of T2D starting from >20 years before diagnosis and including fasting glucose, triglycerides and BMI were evaluated according to yearly means for cases and controls. RESULTS: We identified 28 244 new T2D cases during the study period, with an average 20-year risk of 8.1%. This risk was substantially increased in overweight and obese participants and those with elevated fasting glucose and triglyceride levels, in both men and women. T2D cases had higher mean BMI and fasting glucose and triglyceride levels compared with controls >20 years before diagnosis and the difference in fasting glucose levels increased over time. CONCLUSIONS: Development of T2D is associated with subtle elevations in glucose and lipid levels >20 years before diagnosis. This suggests that diabetogenic processes tied to chronic insulin resistance operate for decades prior to the development of T2D. A simple risk classification can help in early identification of individuals who are at increased risk.

Circulating gamma-glutamyl transferase and development of specific breast cancer subtypes: findings from the Apolipoprotein Mortality Risk (AMORIS) cohort.

BACKGROUND: Different etiological pathways may precede development of specific breast cancer subtypes and impact prevention or treatment strategies. We investigated the association between gamma-glutamyl transferase (GGT) and development of specific breast cancer subtypes based on oestrogen receptor (ER), progesterone receptor (PR) and HER2 status. METHODS: We included 231,283 cancer-free women in a Swedish cohort. Associations between GGT and breast cancer subtypes were investigated with nested case-control and case-case analyses. We used logistic regression models to assess serum GGT in relation to breast cancer subtype, based on individual and combined receptor status. RESULTS: Positive associations were found between serum GGT and development of ER+, ER- and PR+ breast cancers compared to controls (odds ratio (OR) 1.14 (95% confidence interval (CI) 1.08-1.19), 1.11 (1.01-1.23) and 1.18 (1.12-1.24), respectively) and of ER+/PR+ tumours. We found inverse associations between GGT levels and PR- breast cancers compared to PR+ (OR 0.87 (0.80-0.95)), between ER+/PR- tumours compared to ER+/PR+ tumours and between ER-/PR-/HER+ compared to ER+/HER2 or PR+/HER2 tumours (OR 0.55 (95% CI 0.34-0.90). CONCLUSION: The observed associations between pre-diagnostic serum GGT and different breast cancer subtypes may indicate distinct underlying pathways and require further investigations to tease out their clinical implications.

The association between individual metabolic syndrome components, primary liver cancer and cirrhosis: A study in the Swedish AMORIS cohort.

Metabolic syndrome (MetS) is associated with non-alcoholic fatty liver disease, which may progress to cirrhosis, a significant risk factor of hepatocellular carcinoma (HCC), the commonest malignant primary liver cancer (PLC). We investigated the association between the individual components of MetS (lipids, apolipoproteins, raised glucose, diabetes and obesity), PLC and cirrhosis. A total of 509,436 participants from the Swedish AMORIS cohort, recruited between January 1985 and December 1996 (end-date December 2011), aged ≥20 with baseline triglycerides (TG), total cholesterol (TC), glucose and liver enzymes were included. Those with baseline benign liver tumours, PLC or cirrhosis were excluded. Multivariate Cox regression, adjusted for age, gender, socio-economic status, liver disease (excluding cirrhosis) and MetS factors were used to estimate the association with PLC and cirrhosis. There were 766 PLC and 2,775 cirrhosis cases over 13 years. Raised TG, low TC, raised glucose, diabetes and low HDL were associated with an increased risk of developing PLC and cirrhosis. ApoB/ApoA-I ratio were also associated with PLC, whilst low LDL, raised TG/HDL, low ApoA-I and low ApoB were associated with cirrhosis. Obesity was significantly associated with PLC but not cirrhosis. Raised TG, low TC, raised glucose and diabetes showed stronger associations with PLC in participants with cirrhosis but many participants developed PLC without cirrhosis. Individual components of MetS (lipids, apolipoproteins, raised glucose, diabetes and obesity) were associated with an increased risk of developing PLC or cirrhosis. MetS components were more strongly associated with PLC with preceding cirrhosis history but many participants developed PLC without cirrhosis.

Serum inflammatory markers and colorectal cancer risk and survival.

BACKGROUND: Inflammation has been linked with development of some cancers. We investigated systemic inflammation in relation to colorectal cancer incidence and subsequent survival using common serum inflammatory markersDesign:A cohort of men and women aged 20 years and older in greater Stockholm area with serum C-reactive protein (CRP) and albumin measured between 1986 and 1999 were included (n=325 599). A subset of these had baseline measurements of haptoglobin and leukocytes. Multivariable Cox regression was performed to assess risk of colorectal cancer by levels of inflammatory markers, adjusting for potential confounders. Analyses were stratified by circulating glucose, total cholesterol and triglycerides. Overall and CRC-specific death following diagnosis were assessed as secondary outcomes. RESULTS: A total of 4764 individuals were diagnosed with colorectal cancer. A positive association between haptoglobin and colorectal cancer incidence was found (hazard ratio (HR): 1.17; 95% CI: 1.06-1.28). A positive association was also observed with leukocytes (HR: 1.21; 95% CI: 1.03-1.42). No evidence of association was noted between CRP and colorectal cancer risk. Higher risks of all-cause death were seen with haptoglobin and leukocytes levels. Higher haptoglobin levels were linked with an increased risk of colorectal cancer death (HR: 1.19; 95% CI: 1.01-1.41). CONCLUSIONS: Prediagnostic systemic inflammation may impact colorectal cancer incidence and survival; therefore, prompting investigations linking inflammatory pathways preceding colorectal cancer with disease severity and progression.

Glucose and lipoprotein biomarkers and breast cancer severity using data from the Swedish AMORIS cohort.

BACKGROUND: The lipid and glucose metabolisms are postulated as possible intermediary mechanisms in linking obesity and breast cancer (BC). Links between serum lipid and glucose biomarkers and BC risk has been observed in the Swedish Apolipoprotein MORtality RISk (AMORIS) cohort. We conducted a follow-up analysis including information on tumour characteristics. METHODS: One thousand eight hundred twenty-four women diagnosed with BC, with serum biomarker levels of glucose, triglycerides, cholesterol (total, HDL, and LDL), and apolipoproteins A-1 and B recorded in a routine health check at baseline were included. BC severity was split into categories (good, moderate, and poor prognosis) based on ER status, TNM stage, and age at diagnosis. Proportional odds models were used to obtain odds ratios (ORs) and 95% confidence intervals (CI), with the interval time between baseline measurement and BC diagnosis accounted for. RESULTS: Serum glucose and the ApoB/ApoA-1 ratio showed a non-statistically significant positive association with BC severity (proportional OR: 1.25 (95%CI: 0.92-1.70) for glucose (

Serum Calcium and the Risk of Breast Cancer: Findings from the Swedish AMORIS Study and a Meta-Analysis of Prospective Studies.

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.

Prediagnostic serum inflammatory markers in relation to breast cancer risk, severity at diagnosis and survival in breast cancer patients.

Inflammation has been linked to cancer but its role in breast cancer is unclear. We investigated common serum markers of inflammation: C-reactive protein (CRP), albumin, haptoglobin and white blood cells (WBC) in relation to breast cancer incidence, severity and survival. A total of 155179 women aged 20 and older without any history of cancer were selected from a large Swedish cohort. Hazard ratios (HRs) for breast cancer were estimated with Cox regression, adjusting for potential confounders. Ordered and binomial logistic regression models were used to assess the associations of serum inflammatory markers with breast cancer severity and oestrogen receptor (ER) positivity at diagnosis, on the other. Cumulative incidence functions by levels of inflammatory markers were assessed for early death from breast cancer and all causes. During a mean follow-up of 18.3 years, 6606 women were diagnosed with breast cancer, of whom 1474 died. A positive association with incident breast cancer was seen for haptoglobin ≥ 1.4g/l [HR 1.09; 95% confidence interval (CI): 1.00-1.18] compared to lower levels. No association was observed between inflammatory markers and breast cancer severity or ER positivity. Higher haptoglobin was linked to risk of early death from breast cancer (HR: 1.27, 95% CI: 1.02-1.59), whereas higher risk of early death from all causes was additionally found with CRP ≥ 10mg/l (HR: 1.19, 95% CI: 1.04-1.36) and WBC ≥ 10×10(9)/l (HR: 1.57, 1.14-2.16). Our findings indicate that prediagnostic serum inflammatory markers were weakly linked to incident breast cancer but corresponded to worse survival after diagnosis.

Serum lactate dehydrogenase and survival following cancer diagnosis.

BACKGROUND: There is evidence that high level of serum lactate dehydrogenase (LDH) is associated with poorer overall survival in several malignancies, but its link to cancer-specific survival is unclear. METHODS: A total of 7895 individuals diagnosed with cancer between 1986 and 1999 were selected for this study. Multivariable Cox proportional hazards regression was used to assess overall and cancer-specific death by the z-score and clinical categories of serum LDH prospectively collected within 3 years before diagnosis. Site-specific analysis was performed for major cancers. Analysis was repeated by different lag times between LDH measurements and diagnosis. RESULTS: At the end of follow-up, 5799 participants were deceased. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall and cancer-specific death in the multivariable model were 1.43 (1.31-1.56) and 1.46 (1.32-1.61), respectively, for high compared with low prediagnostic LDH. Site-specific analysis showed high LDH to correlate with an increased risk of death from prostate, pulmonary, colorectal, gastro-oesophageal, gynaecological and haematological cancers. Serum LDH assessed within intervals closer to diagnosis was more strongly associated with overall and cancer-specific death. CONCLUSIONS: Our findings demonstrated an inverse association of baseline serum LDH with cancer-specific survival, corroborating its role in cancer progression.

Prediagnostic serum glucose and lipids in relation to survival in breast cancer patients: a competing risk analysis.

BACKGROUND: Abnormal glucose and lipids levels may impact survival after breast cancer (BC) diagnosis, but their association to other causes of mortality such as cardiovascular (CV) disease may result in a competing risk problem. METHODS: We assessed serum glucose, triglycerides (TG) and total cholesterol (TC) measured prospectively 3 months to 3 years before diagnosis in 1798 Swedish women diagnosed with any type of BC between 1985 and 1999. In addition to using Cox regression, we employed latent class proportional hazards models to capture any heterogeneity of associations between these markers and BC death. The latter method was extended to include the primary outcome (BC death) and competing outcomes (CV death and death from other causes), allowing latent class-specific hazard estimation for cause-specific deaths. RESULTS: A lack of association between prediagnostic glucose, TG or TC with BC death was observed with Cox regression. With latent class proportional hazards model, two latent classes (Class I and II) were suggested. Class I, comprising the majority (81.5 %) of BC patients, had an increased risk of BC death following higher TG levels (HR: 1.87, 95 % CI: 1.01-3.45 for every log TG increase). Lower overall survival was observed in Class II, but no association for BC death was found. On the other hand, TC positively corresponded to CV death in Class II, and similarly, glucose to death from other causes. CONCLUSION: Addressing cohort heterogeneity in relation to BC survival is important in understanding the relationship between metabolic markers and cause-specific death in presence of competing outcomes.

Iron metabolism and risk of cancer in the Swedish AMORIS study.

OBJECTIVES: Pre-clinical studies have shown that iron can be carcinogenic, but few population-based studies investigated the association between markers of the iron metabolism and risk of cancer while taking into account inflammation. We assessed the link between serum iron (SI), total-iron binding capacity (TIBC), and risk of cancer by levels of C-reactive protein (CRP) in a large population-based study (n = 220,642). METHODS: From the Swedish Apolipoprotein Mortality Risk (AMORIS) study, we selected all participants (>20 years old) with baseline measurements of serum SI, TIBC, and CRP. Multivariate Cox proportional hazards regression was carried out for standardized and quartile values of SI and TIBC. Similar analyses were performed for specific cancers (pancreatic, colon, liver, respiratory, kidney, prostate, stomach, and breast cancer). To avoid reverse causation, we excluded those with follow-up <3 years. RESULTS: We found a positive association between standardized TIBC and overall cancer [HR 1.03 (95% CI 1.01-1.05)]. No statistically significant association was found between SI and cancer risk except for postmenopausal breast cancer [HR for standardized SI 1.09 (95% CI 1.02-1.15)]. The association between TIBC and specific cancer was only statistically significant for colon cancer [i.e., HR for standardized TIBC: 1.17 (95% CI 1.08-1.28)]. A borderline interaction between SI and levels of CRP was observed only in stomach cancer. CONCLUSIONS: As opposed to pre-clinical findings for serum iron and cancer, this population-based epidemiological study showed an inverse relation between iron metabolism and cancer risk. Minimal role of inflammatory markers observed warrants further study focusing on developments of specific cancers.

Inorganic phosphate and the risk of cancer in the Swedish AMORIS study.

BACKGROUND: Both dietary and serum levels of inorganic phosphate (Pi) have been linked to development of cancer in experimental studies. This is the first population-based study investigating the relation between serum Pi and risk of cancer in humans. METHODS: From the Swedish Apolipoprotein Mortality Risk (AMORIS) study, we selected all participants (> 20 years old) with baseline measurements of serum Pi, calcium, alkaline phosphatase, glucose, and creatinine (n = 397,292). Multivariable Cox proportional hazards regression analyses were used to assess serum Pi in relation to overall cancer risk. Similar analyses were performed for specific cancer sites. RESULTS: We found a higher overall cancer risk with increasing Pi levels in men ( HR: 1.02 (95% CI: 1.00-1.04) for every SD increase in Pi), and a negative association in women (HR: 0.97 (95% CI: 0.96-0.99) for every SD increase in Pi). Further analyses for specific cancer sites showed a positive link between Pi quartiles and the risk of cancer of the pancreas, lung, thyroid gland and bone in men, and cancer of the oesophagus, lung, and nonmelanoma skin cancer in women. Conversely, the risks for developing breast and endometrial cancer as well as other endocrine cancer in both men and women were lower in those with higher Pi levels. CONCLUSIONS: Abnormal Pi levels are related to development of cancer. Furthermore, the in verse association between Pi levels and risk of breast, endometrial and other endocrine cancers may indicate the role of hormonal factors in the relation between Pi metabolism and cancer.

Serum calcium and risk of gastrointestinal cancer in the Swedish AMORIS study.

BACKGROUND: Observational studies have indicated that high calcium intake may prevent colorectal cancer, but as for randomized trials the results are inconclusive. Meanwhile, limited data on the link between serum calcium and cancer risk is available. We investigated the relation between serum calcium and risk of different gastrointestinal cancers in a prospective study. METHODS: A cohort based on 492,044 subjects with baseline information on calcium (mmol/L) and albumin (g/L) was selected from the Swedish Apolipoprotein MOrtality RISk (AMORIS) study. Multivariable Cox proportional hazard models were used to analyse associations between standardised levels, quartiles and age/sex-specific categories of serum calcium and risk of oesophageal, stomach, colon, rectal cancer and also colorectal cancer combined, while taking into account serum albumin and other comorbidities. RESULTS: During 12 years of follow-up, we identified 323 incident oesophageal cancers, 782 stomach cancers, 2519 colon cancers, and 1495 rectal cancers. A positive association was found between albumin-adjusted serum calcium and risk of oesophageal [HR: 4.82 (95% CI: 2.07 - 11.19) for high compared to normal age-specific calcium levels] and colon cancer [e.g. HR: 1.07 (95% CI: 1.00 - 1.14) for every SD increase of calcium] as well as colorectal cancer [e.g. HR: 1.06 (95% CI: 1.02-1.11) for every SD increase of calcium] in women. In men there were similar but weaker non-statistically significant trends. CONCLUSION: The positive relation between serum calcium, oesophageal cancer and colorectal cancer calls for further studies including calcium regulators to evaluate whether there is a true link between calcium metabolism and development of gastrointestinal cancer.

The interplay between lipid profiles, glucose, BMI and risk of kidney cancer in the Swedish AMORIS study.

With exception of cholesterol and total fat intake, associations between lipid biomarkers and kidney cancer have not often been researched. We aimed to assess possible links between lipid profiles and kidney cancer risk in a large prospective cohort study, while also taking into account glucose levels and BMI. A cohort based on 542,924 persons with baseline information on glucose, triglycerides (TGs), total cholesterol (TC) and creatinine was selected from the Swedish Apolipoprotein Mortality Risk study. A subgroup of 85,621 also had baseline measurements of HDL, LDL, apolipoprotein A-I and apoB. Multivariate Cox proportional hazard models were used to analyze associations between quartiles and dichotomized values of these lipid components and kidney cancer risk. During a mean follow-up of 13 years, 958 persons developed kidney cancer. TGs were the only lipid component for which a statistically significant association was found with kidney cancer risk when using both quartiles and a clinical cutoff (hazard ratio: 1.25 (95% CI: 0.99-1.60), 1.29 (1.01-1.66) and 1.66 (1.30-2.13) for the 2nd, 3rd and 4th quartile, compared to the 1st, with p-value for trend: <0.001). The association remained after exclusion of the 95% percentile of TG. Quartiles of glucose were also positively associated with kidney cancer risk, whereas quartiles of TC were negatively associated with kidney cancer risk. This detailed analysis of lipid components only showed a consistent relation between TG levels and kidney cancer risk. Further mechanistic studies are required to assess links between lipid abnormalities and kidney cancer.

Serum calcium and incident and fatal prostate cancer in the Swedish AMORIS study.

BACKGROUND: Observational studies have shown a positive association between intake of dairy products as well as serum levels of calcium and prostate cancer (PCa) risk. We studied the association between serum calcium and PCa while also accounting for levels of albumin, a protein to which calcium is bound. METHODS: A cohort based on 196,022 men with baseline information on calcium (mmol/L) and albumin (g/L) was selected from the Swedish Apolipoprotein MOrtality RISk study. Age-stratified multivariable Cox proportional hazard models were used to analyze associations between calcium and incident and fatal PCa risk. RESULTS: A total of 6,353 men were diagnosed with PCa and 731 died of PCa during mean follow-up of 12 years. A weak negative association was found between levels of calcium or albumin-corrected calcium and PCa risk (HR for quartiles of albumin-corrected calcium: 0.95 (0.89-1.02), 0.93 (0.86-1.00), and 0.91 (0.85-0.98) for the 2nd, 3rd, and 4th quartile compared to the 1st; p for trend: 0.012). BMI did not affect these findings. No association was found between calcium levels and fatal PCa. A positive association between Ca and death was observed when censoring for PCa [HR per SD: 1.14 (1.13-1.16)]. CONCLUSION: The weak negative association between Ca and PCa risk is likely explained by the relation between Ca and death. This illustrates the need to handle competing risks when defining whether Ca is involved in PCa etiology or whether it acts as a marker of other metabolic events in the causal pathway.