Apolipoproteins, lipids and risk of cancer Borgquist, Signe; Butt, Talha; Almgren, Peter ...
International journal of cancer,
June 01 2016, Letnik:
138, Številka:
11
Journal Article
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The epidemiological evidence for an obesity‐cancer association is solid, whereas the association between obesity‐associated lipoprotein levels and cancer is less evident. We investigated circulating ...levels of Apolipoprotein A1 (ApoA1), Apolipoprotein B (ApoB), LDL‐cholesterol (LDL‐C) and HDL‐cholesterol (HDL‐C) and association to risk of overall cancer and common cancer forms. The Malmö Diet and Cancer Study, a population‐based prospective cohort study, enrolled 17,035 women and 11,063 men (1991–1996). Incident cancer cases were ascertained by record linkage with the Swedish Cancer Registry until end of follow‐up, January 1, 2012. Baseline serum levels of ApoA1 and ApoB were analyzed for the entire cohort and HDL‐C and LDL‐C levels in 5,281 participants. Hazard ratios, with 95% confidence interval, were calculated using Cox's proportional hazards analysis. In the entire cohort, none of the exposures were related to overall cancer risk (HRadj ApoA1 = 0.98, 95%CI: 0.95,1.01; HRadj ApoB = 1.01, 95%CI: 0.98–1.04). Among men, ApoB was positively associated with cancer risk (HRadj ApoB = 1.06, 95%CI: 1.01,1.10). Female breast cancer risk was inversely associated with ApoB (HRadj = 0.92, 95%CI: 0.86,0.99). Among both genders, ApoA1 was inversely associated with lung cancer risk (HRadj = 0.88, 95%CI: 0.80,0.97), whereas high ApoB increased lung cancer risk (HRadj = 1.08, 95%CI: 0.99,1.18). Colorectal cancer risk was increased with high ApoB (HRadj = 1.08, 95%CI: 1.01,1.16) among both genders. Apolipoprotein levels were not associated with prostate cancer incidence. Circulating levels of apolipoproteins are associated with overall cancer risk in men and across both genders with breast, lung and colorectal cancer risk. Validation of these findings may facilitate future primary prevention strategies for cancer.
What's new?
Obesity and cancer are associated, although the underlying biological mechanisms are not fully understood. In this population‐based study of 28,098 individuals, incidences of overall cancer and breast, lung and colorectal cancers were found to be associated with circulating levels of apolipoproteins A1 and B (ApoB). The nature of the associations varied. Whereas ApoB was positively linked to cancer risk in men, it was inversely associated with breast cancer risk in women. Meanwhile, no association was found for prostate cancer incidence. The findings may improve the understanding of the obesity‐cancer association and help facilitate primary preventive strategies.
There is substantial genetic predisposition to bladder cancer (BC). Recently, blood pressure (BP) was positively associated with BC risk in men, but the potential interaction with genetic ...susceptibility for BC is unknown. We investigated a weighted genetic risk score (wGRS) of 18 BC genetic variants, BP, and their interaction, in relation to incident urothelial cancer (UC, n = 385) risk in 10,576 men. We used Cox regression, the likelihood ratio test, and the relative excess risk for interaction to calculate hazard ratios (HR) of UC, multiplicative interaction and additive interaction respectively. There was evidence of a positive additive interaction between SBP and the wGRS in relation to aggressive (P = 0.02) but not non-aggressive (P = 0.60) UC. The HR of aggressive UC was for SBP ≥ 140 mmHg and the upper 50% of the wGRS combined 1.72 (95% CI 1.03-2.87) compared to the counterpart group. Additionally, the 20-year risk of aggressive UC in 60 year-old men was 0.78% in the low SBP/low wGRS group and 1.33% in the high SBP/high wGRS group. Our findings support a potential additive interaction between the wGRS and SBP on aggressive UC among men. If replicated, the findings on interaction may provide biological and public health insight to prevent aggressive UC.
Observational studies have shown inconsistent results for the association between blood pressure and cancer risk. We investigated the association in 7 cohorts from Norway, Austria, and Sweden. In ...total, 577799 adults with a mean age of 44 years were followed for, on average, 12 years. Incident cancers were 22184 in men and 14744 in women, and cancer deaths were 8724 and 4525, respectively. Cox regression was used to calculate hazard ratios of cancer per 10-mmHg increments of midblood pressure, which corresponded with 0.7 SDs and, for example, an increment of systolic/diastolic blood pressure of 130/80 to 142/88 mmHg. All of the models used age as the time scale and were adjusted for possible confounders, including body mass index and smoking status. In men, midblood pressure was positively related to total incident cancer (hazard ratio per 10 mmHg increment1.07 95% CI1.04–1.09) and to cancer of the oropharynx, colon, rectum, lung, bladder, kidney, malignant melanoma, and nonmelanoma skin cancer. In women, midblood pressure was not related to total incident cancer but was positively related to cancer of the liver, pancreas, cervix, uterine corpus, and malignant melanoma. A positive association was also found for cancer mortality, with HRs per 10-mmHg increment of 1.12 (95% CI1.08–1.15) for men and 1.06 (95% CI1.02–1.11) for women. These results suggest a small increased cancer risk overall in men with elevated blood pressure level and a higher risk for cancer death in men and women.
While a dose-response relationship between physical activity and risk of diabetes has been demonstrated, few studies have assessed the relative importance of different measures of physical activity ...on diabetes risk. The aim was to examine the association between different self-reported measures of physical activity and risk of type 2 diabetes in a prospective cohort study.
Out of 26,615 adults (45-74 years, 60% women) in the population-based Swedish Malmö Diet and Cancer Study cohort, 3791 type 2 diabetes cases were identified from registers during 17 years of follow-up. Leisure-time (17 activities), occupational and domestic physical activity were assessed through a questionnaire, and these and total physical activity were investigated in relation to type 2 diabetes risk.
All physical activity measures showed weak to modest associations with type 2 diabetes risk. The strongest association was found in the lower end of leisure-time physical activity in dose-response analysis at levels approximately below 22 MET-hrs/week (300 min/week) representing around 40% of the population. Compared with the lowest quintile, the moderate leisure-time physical activity category had a 28% (95% CI: 0.71, 0.87) decreased risk of type 2 diabetes. Total physical activity showed a similar, but weaker, association with diabetes risk as to that of leisure-time physical activity. Domestic physical activity was positively and linearly related to diabetes risk, HR = 1.11 (95% CI: 0.99, 1.25) comparing highest to lowest quintile. There was no association between occupational physical activity and diabetes risk.
A curvilinear association was observed between leisure-time physical activity and risk of diabetes. Beyond a threshold level of approximately 22 MET-hrs/week or 300 min/week, no additional risk reduction was observed with increase in physical activity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Adolescence is a period of rapid prostatic growth, yet is understudied for susceptibility for future risk of prostate cancer. We examined cardiorespiratory fitness (CRF) in late adolescence in ...relation to long-term prostate cancer risk.
A population-based cohort study was conducted of all 699,125 Swedish military conscripts during 1972-1985 (97%-98% of 18-year-old men) in relation to risk of prostate cancer overall, aggressive prostate cancer, and prostate cancer mortality during 1998-2017 (ages 50-65 years). CRF was measured by maximal aerobic workload, and prostate cancer was ascertained using the National Prostate Cancer Register. Muscle strength was examined as a secondary predictor.
In 38.8 million person-years of follow-up, 10,782 (1.5%) men were diagnosed with prostate cancer. Adjusting for sociodemographic factors, height, weight, and family history of prostate cancer, high CRF was associated with a slightly increased risk of any prostate cancer highest vs. lowest quintile: incidence rate ratio (IRR), 1.10; 95% CI, 1.03-1.19;
= 0.008, but was neither significantly associated with aggressive prostate cancer (1.01; 0.85-1.21;
= 0.90) nor prostate cancer mortality (1.24; 0.73-2.13;
= 0.42). High muscle strength also was associated with a modestly increased risk of any prostate cancer (highest vs. lowest quintile: IRR, 1.14; 95% CI, 1.07-1.23;
< 0.001), but neither with aggressive prostate cancer (0.88; 0.74-1.04;
= 0.14) nor prostate cancer mortality (0.81; 0.48-1.37;
= 0.43).
High CRF or muscle strength in late adolescence was associated with slightly increased future risk of prostate cancer, possibly related to increased screening, but neither with risk of aggressive prostate cancer nor prostate cancer mortality.
These findings illustrate the importance of distinguishing aggressive from indolent prostate cancer and assessing for potential detection bias.
Prospective studies have indicated that elevated blood glucose levels may be linked with increased cancer risk, but the strength of the association is unclear. We examined the association between ...blood glucose and cancer risk in a prospective study of six European cohorts.
The Metabolic syndrome and Cancer project (Me-Can) includes cohorts from Norway, Austria, and Sweden; the current study included 274,126 men and 275,818 women. Mean age at baseline was 44.8 years and mean follow-up time was 10.4 years. Excluding the first year of follow-up, 18,621 men and 11,664 women were diagnosed with cancer, and 6,973 men and 3,088 women died of cancer. We used Cox regression models to calculate relative risk (RR) for glucose levels, and included adjustment for body mass index (BMI) and smoking status in the analyses. RRs were corrected for regression dilution ratio of glucose. RR (95% confidence interval) per 1 mmol/l increment of glucose for overall incident cancer was 1.05 (1.01-1.10) in men and 1.11 (1.05-1.16) in women, and corresponding RRs for fatal cancer were 1.15 (1.07-1.22) and 1.21 (1.11-1.33), respectively. Significant increases in risk among men were found for incident and fatal cancer of the liver, gallbladder, and respiratory tract, for incident thyroid cancer and multiple myeloma, and for fatal rectal cancer. In women, significant associations were found for incident and fatal cancer of the pancreas, for incident urinary bladder cancer, and for fatal cancer of the uterine corpus, cervix uteri, and stomach.
Data from our study indicate that abnormal glucose metabolism, independent of BMI, is associated with an increased risk of cancer overall and at several cancer sites. Our data showed stronger associations among women than among men, and for fatal cancer compared to incident cancer. Please see later in the article for the Editors' Summary.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The association between blood pressure (BP) and bladder cancer (BC) risk remains unclear with confounding by smoking being of particular concern. We investigated the association between BP and BC ...risk among men using conventional survival-analysis, and by Mendelian Randomization (MR) analysis in an attempt to disconnect the association from smoking. We additionally investigated the interaction between BP and N-acetyltransferase-2 (NAT2) rs1495741, an established BC genetic risk variant, in the association. Populations consisting of 188,167 men with 502 incident BC's in the UK-biobank and 27,107 men with 928 incident BC's in two Swedish cohorts were used for the analysis. We found a positive association between systolic BP and BC risk in Cox-regression survival analysis in the Swedish cohorts, (hazard ratio HR per standard deviation SD: 1.14 95% confidence interval 1.05-1.22) and MR analysis (odds ratio per SD: 2-stage least-square regression, 7.70 1.92-30.9; inverse-variance weighted estimate, 3.43 1.12-10.5), and no associations in the UK-biobank (HR systolic BP: 0.93 0.85-1.02; MR OR: 1.24 0.35-4.40 and 1.37 0.43-4.37, respectively). BP levels were positively associated with muscle-invasive BC (MIBC) (HRs: systolic BP, 1.32 1.09-1.59; diastolic BP, 1.27 1.04-1.55), but not with non-muscle invasive BC, which could be analyzed in the Swedish cohorts only. There was no interaction between BP and NAT2 in relation to BC on the additive or multiplicative scale. These results suggest that BP might be related to BC, more particularly MIBC. There was no evidence to support interaction between BP and NAT2 in relation to BC in our study.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To investigate the association between total serum cholesterol (TSC) and cancer incidence in the Metabolic syndrome and Cancer project (Me-Can).
Me-Can consists of seven cohorts from Norway, Austria, ...and Sweden including 289,273 male and 288,057 female participants prospectively followed up for cancer incidence (n = 38,978) with a mean follow-up of 11.7 years. Cox regression models with age as the underlying time metric were used to estimate hazard ratios (HR) and their 95% confidence intervals (CI) for quintiles of cholesterol levels and per 1 mmol/l, adjusting for age at first measurement, body mass index (BMI), and smoking status. Estimates were corrected for regression dilution bias. Furthermore, we performed lag time analyses, excluding different times of follow-up, in order to check for reverse causation.
In men, compared with the 1st quintile, TSC concentrations in the 5th quintile were borderline significantly associated with decreasing risk of total cancer (HR = 0.94; 95%CI: 0.88, 1.00). Significant inverse associations were observed for cancers of the liver/intrahepatic bile duct (HR = 0.14; 95%CI: 0.07, 0.29), pancreas cancer (HR = 0.52, 95% CI: 0.33, 0.81), non-melanoma of skin (HR = 0.67; 95%CI: 0.46, 0.95), and cancers of the lymph-/hematopoietic tissue (HR = 0.68, 95%CI: 0.54, 0.87). In women, hazard ratios for the 5th quintile were associated with decreasing risk of total cancer (HR = 0.86, 95%CI: 0.79, 0.93) and for cancers of the gallbladder (HR = 0.23, 95%CI: 0.08, 0.62), breast (HR = 0.70, 95%CI: 0.61, 0.81), melanoma of skin (HR = 0.61, 95%CI: 0.42, 0.88), and cancers of the lymph-/hematopoietic tissue (HR = 0.61, 95%CI: 0.44, 0.83).
TSC was negatively associated with risk of cancer overall in females and risk of cancer at several sites in both males and females. In lag time analyses some associations persisted, suggesting that for these cancer sites reverse causation did not apply.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Serum potassium levels have been positively associated with cardiovascular mortality, but little is known about the association with cancer mortality and death due to other causes. We examined ...whether serum levels of potassium were associated with long-term mortality in a healthy cohort.
Oslo Ischemia Study invited 2341 initially healthy men aged 40-59 years with no use of medication to a comprehensive health survey in 1972. Fasting serum level of potassium (mmol/L) was ascertained at baseline for 1989 men. We have complete follow-up for death throughout 2017. Cox proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) and adjusted for multiple confounders.
After a median follow-up of 30 years (interquartile range 21.2-38.7), 1736 deaths were observed, of which 494 were cancer deaths, 688 cardiovascular deaths, and 536 deaths related to other causes. Restricted cubic spline analysis showed that potassium level was linearly and positively associated with long-term cancer mortality; HR per mmol/L 1.8, 95% CI 1.4-2.4. Compared with low levels of potassium (≤ 4.0 mmol/L), men with high levels (≥4.6 mmol/L) showed a significantly 78% higher risk of cancer death. A positive linear association was found for all-cause mortality (HR per mmol/L 1.6, 95% CI 1.4-1.8), and for cardiovascular (HR per mmol/L 1.4, 95% CI 1.1-1.7) and other cause mortality (HR per mmol/L 1.7, 95% CI 1.3-2.2).
These findings suggest that serum potassium level appears to predict long-term mortality in healthy middle-aged men, and it might imply future surveillance strategies for individuals with high serum potassium levels.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Initial studies have indicated diabetes and obesity to be risk factors for hepatocellular carcinoma; but the association between other metabolic risk factors and primary liver cancer (PLC) has not ...been investigated. The metabolic syndrome and cancer project (Me‐Can) includes cohorts from Norway, Austria and Sweden with data on 578,700 subjects. We used Cox proportional hazard models to calculate relative risks (RRs) of PLC by body mass index (BMI), blood pressure and plasma levels of glucose, cholesterol and triglycerides as continuous standardized variables (z‐score with mean = 0 and standard deviation (SD) = 1) and their standardized sum of metabolic syndrome (MetS) z‐score. RRs were corrected for random error in measurements. During an average follow‐up of 12.0 years (SD = 7.8), 266 PLCs were diagnosed among cohort members. RR of liver cancer per unit increment of z‐score adjusted for age, smoking status and BMI and stratified by birth year, sex and sub‐cohorts, was for BMI 1.39 (95% confidence interval (CI) 1.24–1.58), mid blood pressure 2.08 (0.95–4.73), blood glucose 2.13 (1.55–2.94) cholesterol 0.62 (0.51–0.76) and serum triglycerides 0.85 (0.65–1.10). The RR per one unit increment of the MetS z‐score was 1.35 (1.12–1.61). BMI, glucose and a composite MetS score were positively and cholesterol negatively associated with risk of liver cancer.
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