| 1. |
- Fritz, Josef, et al.
(författare)
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Insulin resistance measured by the triglyceride-glucose index and risk of obesity-related cancers : An epidemiological investigation in more than 500,000 individuals.
- 2019
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 37:15, s. 1552-1552
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: The role of insulin resistance as a mediator in the association of body mass index (BMI) with site-specific cancer risk has, to our knowledge, never been systematically quantified. We aimed to determine to what extent insulin resistance measured as the logarithmized triglyceride glucose product (TyG index) mediates the effect of BMI on risk of obesity-related cancers. Methods: A total of 510,471 individuals from six European cohorts with a mean age of 43.1 years were included in the study. We fitted Cox models, adjusted for relevant confounders, to investigate associations of TyG index with ten common obesity-related cancer sites, and quantified the proportion of the effect of BMI mediated through TyG index. Results: During a median follow-up of 17.2 years, 16 052 individuals developed obesity-related cancers. TyG index was associated with the risk of cancers of the kidney (hazard ratio (HR) per one standard deviation increase 1.13, 95% confidence interval: 1.07-1.20), liver (1.13, 1.04-1.23), pancreas (1.12, 1.06-1.19), colon (1.07, 1.03-1.10), and rectum (1.09, 1.04-1.14). Substantial proportions of the effect of BMI were mediated by TyG index for cancers of the pancreas (42%), rectum (34%), and colon (20%); smaller proportions for kidney (15%) and liver (11%); none for endometrium, ovary and breast (postmenopausal). Conclusions: In this pooled cohort study including more than 500,000 individuals, insulin resistance measured as the logarithmized triglyceride glucose product significantly mediated the effect of overweight and obesity on risk of cancers of the kidney, liver, pancreas, colon, and rectum. In contrast, insulin resistance did not mediate the risk for cancers of the endometrium, ovary and breast. Our results confirm a promoting role of insulin resistance in the pathogenesis of gastrointestinal cancers. Although often claimed, insulin resistance does not appear to connect excess body weight with cancers of the female reproductive organs.
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| 2. |
- Stocks, Tanja, 1977-, et al.
(författare)
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Blood glucose and risk of incident and fatal cancer in the metabolic syndrome and cancer project (Me-Can) : analysis of six prospective cohorts.
- 2009
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 6:12, s. e1000201-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundProspective studies have indicated that elevated blood glucose levels may increase the risk of cancer, 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. Methods and Findings 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.ConclusionsData from our study indicate that abnormal glucose metabolism, independently 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.
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| 3. |
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| 4. |
- Stocks, Tanja, 1977-, et al.
(författare)
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Components of the metabolic syndrome and colorectal cancer risk : a prospective study
- 2008
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 32:2, s. 304-314
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the relation of well-known factors of the metabolic syndrome (MetS) as well as related circulating factors, with risk of colorectal cancer. Methods: We performed a case control study of 306 colorectal cancer cases and 595 matched controls nested in the Northern Sweden Health and Disease Cohort. Levels of C-peptide, glycated haemoglobin (HbA1c), leptin and adiponectin were measured in cryopreserved samples. Body mass index (BMI), systolic and diastolic blood pressure and fasting and post-load plasma glucose, had been measured in a subcohort. Conditional logistic regression was used to calculate odds ratios (OR) of disease, including risk assessments for the MetS factors: obesity (BMI>30 kg m-2), hypertension (blood pressure 140/90 mmHg or use of anti-hypertensive drugs) and hyperglycaemia (fasting glucose 6.1 mmol l-1 or post-load glucose in capillary plasma 8.9 mmol l-1). Results: None of the studied variables were significantly associated with risk across quartiles. Presence of obesity, hypertension and hyperglycaemia significantly increased the risk of colorectal cancer; OR for three vs null factors was 2.57 (95% Confidence Interval [CI] 1.20–5.52; P trend=0.0021), as compared to a 30 to 70% increased risk for the factors in single. Similarly, top decile levels of C-peptide, HbA1c and leptin/adiponectin ratio were associated with an increased risk; ORs for top vs deciles 1–9 were 1.56 (95% CI 0.93–2.62; P=0.090), 1.83 (95% CI 1.00–3.36; P=0.051) and 1.50 (95% CI 0.83–2.71; P=0.18), respectively. Conclusions: Our study support the view that components of the MetS increase risk of colorectal cancer, and further suggests that only very high levels of metabolic factors confer an increased risk.
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| 5. |
- Stocks, Tanja, 1977-, et al.
(författare)
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Insulin resistance is inversely related to prostate cancer : a prospective study in Northern Sweden
- 2007
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 120:12, s. 2678-2686
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Tidskriftsartikel (refereegranskat)abstract
- Factors related to insulin resistance have been implicated in prostate cancer development, however, few analytical studies support such an association. We performed a case control study on 392 prostate cancer cases and 392 matched controls nested in a prospective cohort in Northern Sweden. Plasma concentrations of C-peptide, leptin, glycated haemoglobin (HbA1c) and fasting and post-load glucose were analysed and homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. Conditional logistic regression analyses were used to calculate odds ratios (OR) of prostate cancer. High levels of C-peptide, HOMA-IR, leptin and HbA1c were associated with significant decreases in risk of prostate cancer, with ORs for top vs. bottom quartile for C-peptide of 0.59 (95% Confidence Interval [CI], 0.40-0.89; ptrend = 0.008), HOMA-IR 0.60 (95% CI, 0.38-0.94; ptrend = 0.03), leptin 0.55 (95% CI, 0.36-0.84; ptrend = 0.006) and HbA1c 0.56 (95% CI, 0.35-0.91; ptrend = 0.02). All studied factors were strongly inversely related to risk among men less than 59 years of age at blood sampling, but not among older men, with a significant heterogeneity between the groups for leptin (pheterogeneity = 0.006) and fasting glucose (pheterogeneity = 0.03). C-peptide and HOMA-IR were strongly inversely related to non-aggressive cancer but were non-significantly positively related to risk of aggressive disease (pheterogeneity = 0.007 and 0.01, respectively). Our data suggest that androgens, which are inversely associated with insulin resistance, are important in the early prostate cancer development, whereas insulin resistance related factors may be important for tumour progression.
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| 6. |
- Stocks, Tanja, 1977-
(författare)
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Metabolic factors and cancer risk : prospective studies on prostate cancer, colorectal cancer, and cancer overall
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: A large number of prospective studies have shown that overweight and diabetes are related to an increased risk of many cancers, including colorectal cancer. In contrast, diabetes has been related to a decreased risk of prostate cancer, and overweight has been related to an increased risk of fatal, but not of incident, prostate cancer. Data from studies on metabolic factors related to overweight and diabetes, and the association with cancer risk, are limited. Aim: The aim of this thesis was to study metabolic factors in relation to risk of prostate cancer (paper I and III), colorectal cancer (paper II and V), and cancer overall (paper VI). Methods: Study designs were i) case-control studies, nested within the Northern Sweden Health and Disease Cohort (paper I and II), and ii) cohort studies of the Swedish Construction Workers cohort (paper III), and the Metabolic syndrome and Cancer project (Me-Can) comprising seven European cohorts (paper V and VI). Paper IV was a descriptive paper of Me-Can. Results, prostate cancer: In paper I, increasing levels of several factors related to insulin resistance (insulin, insulin resistance index, leptin, HbA1c, and glucose) were associated with a decreased risk of overall incident prostate cancer, and the associations were stronger for non-aggressive tumours. In paper III, increasing levels of blood pressure was associated with a significant decreased risk of overall incident prostate cancer and of non-aggressive tumours. Body mass index (BMI) was significantly positively related to fatal prostate cancer. Results, colorectal cancer: In paper II, obesity, hypertension, and hyperglycaemia, were associated with an increased risk of colorectal cancer, and presence of two or three of these factors was associated with a higher risk than the presence of one single factor. In paper V, BMI was associated with a significant linear positive association with risk of colorectal cancer in men and women, and significant positive associations were also found in men for blood pressure and triglycerides. A high metabolic syndrome score, based on levels of BMI, blood pressure, glucose, cholesterol, and triglycerides, was associated with a significant increased risk of colorectal cancer in men and women. The association was stronger than for any of the factors in single, but there was no evidence of a positive interaction between these metabolic factors. Results, cancer overall: Blood glucose was significantly positively associated with risk of incident and fatal cancer overall, and at several specific sites. The associations were stronger in women than in men, and for fatal than for incident cancer. Conclusions: Results from these studies indicate that elevated blood glucose is related to an increased risk of cancer overall and at several specific sites, and further, that overweight and metabolic aberrations increase the risk of colorectal cancer in an additive way. The association with prostate cancer seems to be more complex; insulin resistance and high blood pressure were in our studies related to a decreased risk of overall incident prostate cancer and of non-aggressive tumours, whereas overweight increased the risk of fatal prostate cancer.
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| 7. |
- Stocks, Tanja, 1977-, et al.
(författare)
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Metabolic factors and risk of colorectal cancer in the metabolic syndrome and cancer project (Me-Can)
- 2011
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Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 117:11, s. 2398-2407
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Tidskriftsartikel (refereegranskat)abstract
- Background The metabolic syndrome (MetS) has been related to an increased risk of colorectal cancer in some small studies, but it is unknown which factors in the MetS that are most strongly related to risk, and if there is an interaction between factors. Methods and Findings In the Metabolic syndrome and Cancer project (Me-Can), data on body mass index (BMI), blood pressure, and blood levels of glucose, cholesterol, and triglycerides were available in 289,866 men and 288,834 women. Mean age at baseline was 44.0 years and mean follow-up time was 12.0 years. During follow-up, 2,834 men and 1,861 women were diagnosed with colorectal cancer. We used Cox regression models to calculate relative risk (RR) of colorectal cancer by exposures transformed into Z scores (mean = 0, standard deviation = 1), and for a MetS Z score, and used regression calibration to correct exposure levels for random error in measurement. Significant increases in risk per one unit increment of factors were observed in men for BMI, RR 1.07 (95% confidence interval, 1.02-1.13), blood pressure, RR 1.10 (1.02-1.18), and triglycerides, RR 1.17 (1.06-1.28), and in women for BMI, RR 1.08 (1.01-1.15). The RR of colorectal cancer per one unit increment of the MetS Z score was 1.24 (1.18-1.31) in men, and 1.14 (1.06-1.22) in women. There was no significant positive interaction for any combination of two metabolic factors. Associations between metabolic factors and risk of fatal colorectal cancer were similar to those for incident cancer. Conclusions Our data add further evidence for an association between factors in the MetS, in single and combined, and risk of colorectal cancer. Our data do not support an interaction between factors in the MetS on risk.
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