| 1. |
- Friberg, Emilie, et al.
(författare)
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Coffee drinking and risk of endometrial cancer-A population-based cohort study
- 2009
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Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 125:10, s. 2413-2417
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Tidskriftsartikel (refereegranskat)abstract
- Coffee drinking has been reported to have beneficial effects on insulin resistance, which has been directly associated with endometrial cancer. Although I relationship between coffee consumption and endometrial cancer risk is biologically plausible, this hypothesis has been previously explored in only 2 prospective studies, with a small number of cases. We used data from the Swedish Mammography Cohort, a population-based prospective cohort study of 60,634 women. During 17.6 years of follow-up 677 participants were diagnosed with incident endometrial cancer (adenocarcinoma). We examined the association between self-reported coffee consumption (at baseline 1987-90 and in 1997) and endometrial cancer risk using Cox proportional hazards models. Each additional cut) (200 g) of coffee per day was associated with 11 rate ratio (RR) of 0.90 [95% confidence interval (CI), 0.83-0.97]. In women drinking 4 or more cups of coffee a day, file RR For the risk reduction of endometrial cancer was 0.75 (95% CL 0.58-0.97) when compared with those who drank I cup or less. The association seemed largely confined to overweight and obese women, who showed a respective risk reduction of 12% (95% Cl, 0-23%) and 20% (95% CI, 7-31%) for every cup or coffee. but was not observed among normal-weight women. There,vas I statistically significant interaction between coffee consumption and body mass index (p(interaction) < 0.001). These data indicate that coffee consumption may be associated with decreased risk of endometrial cancer. especially among women with excessive body weight. If confirmed by other prospective studies. these results are of major public health significance. (C) 2009 UICC
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| 2. |
- Friberg, Emilie, et al.
(författare)
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Diabetes and risk of endometrial cancer : A population-based prospective cohort study
- 2007
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - Karolinska Inst, Div Nutr Epidemiol, Natl Inst Environm Med, SE-17177 Stockholm, Sweden. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab,Dept Med, Boston, MA 02215 USA. : AMER ASSOC CANCER RESEARCH. - 1055-9965 .- 1538-7755. ; 16:2, s. 276-280
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Tidskriftsartikel (refereegranskat)abstract
- Although there is accumulating evidence that hyperinsulinemia in the context of insulin resistance is associated with carcinogenesis, only one prospective study of endometrial cancer incidence, in relation to diabetes, addressed this issue and showed no significant positive association. No previous study has investigated whether physical activity can modify the association between diabetes and endometrial cancer. We examined the association between diabetes and incidence of endometrial cancer and the potential effect modification by obesity and physical activity in the Swedish Mammography Cohort, a prospective cohort of 36,773 women, including 225 incident endometrial adenocarcinoma cases. After adjustments, the relative risk (RR) for endometrial cancer among women with diabetes comparing with nondiabetic women was 1.94 [95% confidence interval (95% CI), 1.23-3.08]. Among obese diabetics, the RR was 6.39 (95% CI, 3.28-12.06) compared with nonobese nondiabetic women. Among diabetics with low physical activity, the RR for endometrial cancer was 2.80 (95% CI, 1.62-4.85) compared with physically active nondiabetic women. Obese diabetics with low physical activity had a RR of 9.61 (95% CI, 4.66-19.83) compared with normal weight nondiabetic women with high physical activity. Diabetes was associated with a 2-fold increased risk, and combination of diabetes with obesity and low physical activity was associated with a further increased risk for endometrial cancer. Interventions to reduce body weight and increase physical activity may have important implications in terms of prevention of endometrial cancer and future management of diabetic subjects.
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| 3. |
- Friberg, Emilie, et al.
(författare)
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Physical activity and risk of endometrial cancer : A population-based prospective cohort study
- 2006
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - Karolinska Inst, Div Nutr Epidemiol, Natl Inst Environm Med, SE-17177 Stockholm, Sweden. Harvard Univ, Sch Med, Div Endocrinol Diabet & Metab, Dept Med,Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. : AMER ASSOC CANCER RESEARCH. - 1055-9965 .- 1538-7755. ; 15:11, s. 2136-2140
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Tidskriftsartikel (refereegranskat)abstract
- Physical activity is involved in the regulation of metabolic and hormonal pathways and is one of the factors important for the maintenance of body weight; obesity is a risk factor for endometrial cancer. A connection between physical activity and endometrial cancer risk through hormonal mechanisms, possibly mediated by body weight, is biologically plausible. Only one study has investigated total physical activity, and no previous study has examined leisure time inactivity directly. We investigated the association of total physical activity and different types of physical activity with risk of endometrial cancer in the Swedish Mammography Cohort, a population-based prospective cohort, including 33,723 women and 199 endometrial cancer cases. After adjustments for potential confounders (age, body mass index, parity, history of diabetes, total fruit and vegetable intake, and education), the relative risks for endometrial cancer for the second to fourth quartile of total physical activity compared with the lowest one were 0.80 [95% confidence interval (95% CI), 0.54-1.18], 0.87 (95% CI, 0.59-1.28), and 0.79 (95% CI, 0.53-1.17). High leisure time inactivity (watching TV/sitting >= 5 hours daily) compared with low was associated with increased risk of endometrial cancer (relative risk, 1.66; 95% CI, 1.05-2.61). The associations were not modified by body mass index. Findings from this study suggest that total physical activity is weakly inversely associated with endometrial cancer risk and that leisure time inactivity is statistically significantly associated with increased risk for endometrial cancer.
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| 4. |
- Giontella, Alice, et al.
(författare)
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Renoprotective effects of genetically proxied fibroblast growth factor 21 : Mendelian randomization, proteome-wide and metabolome-wide association study
- 2023
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Ingår i: Metabolism. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 145
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fibroblast growth factor 21 (FGF21) has demonstrated efficacy for reducing liver fat and reversing non-alcoholic steatohepatitis in phase 2 clinical trials. It is also postulated to have anti-fibrotic effects and therefore may be amenable to repurposing for the prevention and treatment of chronic kidney disease (CKD).Methods: We leverage a missense genetic variant, rs739320 in the FGF21 gene, that associates with magnetic resonance imaging-derived liver fat as a clinically validated and biologically plausible instrumental variable for studying the effects of FGF21 analogs. Performing Mendelian randomization, we ascertain associations between instrumented FGF21 and kidney phenotypes, cardiometabolic disease risk factors, as well as the circulating proteome (Somalogic, 4907 aptamers) and metabolome (Nightingale platform, 249 metabolites).Results: We report consistent renoprotective associations of genetically proxied FGF21 effect, including higher glomerular filtration rates (p = 1.9 x 10(-4)), higher urinary sodium excretion (p = 5.1 x 10(-11)), and lower urine albumin-creatinine ratio (p = 3.6 x 10(-5)). These favorable effects translated to lower CKD risk (odds ratio per rs739320 C-allele, 0.96; 95%CI, 0.94-0.98; p = 3.2 x 10(-4)). Genetically proxied FGF21 effect was also associated with lower fasting insulin, waist-to-hip ratio, blood pressure (systolic and diastolic BP, p < 1.0 x 10(- 07)) and blood lipid (low-density lipoprotein cholesterol, triglycerides and apolipoprotein B, p < 6.5 x 10(-24)) profiles. The latter associations are replicated in our metabolome-wide association study. Proteomic perturbations associated with genetically predicted FGF21 effect were consistent with fibrosis reduction.Conclusion: This study highlights the pleiotropic effects of genetically proxied FGF21 and supports a re-purposing opportunity for the treatment and prevention of kidney disease specifically. Further work is required to
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| 5. |
- Larsson, Susanna C., et al.
(författare)
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Body fatness associations with cancer : evidence from recent epidemiological studies and future directions
- 2022
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Ingår i: Metabolism. - : Elsevier. - 0026-0495 .- 1532-8600. ; 137
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Forskningsöversikt (refereegranskat)abstract
- This narrative review highlights current evidence linking greater body fatness to risk of various cancers, with focus on evidence from recent large cohort studies and pooled analyses of cohort studies as well as Mendelian randomization studies (which utilized genetic variants associated with body mass index to debrief the causal effect of higher body fatness on cancer risk). This review also provides insights into the biological mechanisms underpinning the associations. Data from both observational and Mendelian randomization studies support the associations of higher body mass index with increased risk of many cancers with the strongest evidence for digestive system cancers, including esophageal, stomach, colorectal, liver, gallbladder, and pancreatic cancer, as well as kidney, endometrial, and ovarian (weak association) cancer. Evidence from observational studies sug-gests that greater body fatness has contrasting effects on breast cancer risk depending on menopausal status and on prostate cancer risk depending on disease stage. Experimental and Mendelian randomization studies indicate that adiponectin, insulin, and sex hormone pathways play an important role in mediating the link between body fatness and cancer risk. The possible role of specific factors and pathways, such as other adipocytokines and hormones and the gut microbiome in mediating the associations between greater body fatness and cancer risk is yet uncertain and needs investigation in future studies. With rising prevalence of overweight and obesity worldwide, the proportion of cancer caused by excess body fatness is expected to increase. There is thus an urgent need to identify efficient ways at the individual and societal level to improve diet and physical activity patterns to reduce the burden of obesity and accompanying comorbidities, including cancer.
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| 6. |
- Larsson, Susanna C., et al.
(författare)
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Circulating lipoprotein(a) levels and health outcomes : Phenome-wide Mendelian randomization and disease-trajectory analyses
- 2022
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Ingår i: Metabolism. - : Elsevier. - 0026-0495 .- 1532-8600. ; 137
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Lipoprotein(a) [Lp(a)] is a risk factor for atherosclerotic and valvular diseases, but its possible role in other diseases has not yet been established. We conducted phenome-wide Mendelian randomization and disease-trajectory analyses to assess any associations of circulating Lp(a) levels with a broad range of diseases.METHODS: A weighted polygenic risk score was constructed using independent genetic variants in the LPA gene and with an established effect on Lp(a) levels. The PheWAS analysis included 1081 phenotype outcomes ascertained among 385,917 White participants of the UK Biobank. Novel findings were investigated in MR analysis using data from the FinnGen consortium. Disease-trajectory and comorbidity analyses were further conducted to explore the sequential patterns of multiple morbidities related to high circulating Lp(a) levels.RESULTS: PheWAS revealed statistically significant associations of higher circulating Lp(a) levels with increased risk of a large number of circulatory system diseases (including various cardiac diseases, peripheral vascular disease, hypertension, and valvular and cerebrovascular diseases) as well as some endocrine/metabolic diseases (including hyperlipidemia, hypercholesterolemia, disorders of lipoid metabolism, and type 2 diabetes), genitourinary system diseases (renal failure), and hematologic diseases (including different types of anemia). Two-sample MR analysis supported the association between Lp(a) and risk of anemia, showed a suggestive association with type 2 diabetes, but found no association with renal failure. Disease-trajectory and comorbidity analyses identified 3 major sequential patterns of multiple morbidities, mainly in the cardiovascular, metabolic, and mental disorders, related to high circulating Lp(a) levels.CONCLUSIONS: Genetically predicted higher circulating Lp(a) levels were associated with increased risk of many circulatory system diseases and anemia. Additionally, this study identified three major sequential patterns of multiple morbidities related to high Lp(a).
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| 7. |
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| 8. |
- Larsson, Susanna C., et al.
(författare)
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Genome-wide association and Mendelian randomization study of fibroblast growth factor 21 reveals causal associations with hyperlipidemia and possibly NASH
- 2022
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Ingår i: Metabolism. - : Elsevier. - 0026-0495 .- 1532-8600. ; 137
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fibroblast growth factor 21 (FGF21) is a hepatokine that produces metabolic benefits, such as improvements of lipid profile. We performed a genome-wide association study (GWAS) to identify genetic variants associated with circulating FGF21 and investigated the causal effects of FGF21 on pertinent outcomes using Mendelian randomization (MR).Methods: We conducted a GWAS testing similar to 7.8 million DNA sequence variants with circulating FGF21 in a discovery cohort of 6259 Swedish adults with replication in 4483 Swedish women. We then performed two-sample MR analyses of genetically predicted circulating FGF21 in relation to alcohol and nutrient intake, cardiovascular and metabolic biomarkers and diseases, and liver function biomarkers using publicly available GWAS summary statistics data.Results: Our GWAS identified multiple single-nucleotide polymorphisms with genome-wide significant associations (P < 5 x 10(-8)) with circulating FGF21 on chromosomes 2 and 19 in or near the GCKR and FGF21 genes, respectively. The strongest signal at the FGF21 locus (rs2548957, beta = 0.181, P < 2.18 x 10(-42)) displayed in twosample MR analyses robust associations with lower alcohol intake, lower circulating low-density lipoprotein cholesterol, apolipoprotein B, C-reactive protein, gamma-glutamyl transferase, and galectin-3 concentrations, and higher circulating insulin-like growth factor-I and alkaline phosphatase concentrations after correcting for multiple testing (P < 0.0018) whereas associations with fat mass, type 2 diabetes, and cardiovascular disease were largely null.Conclusions: We identified robust associations of certain genetic variants in or near the GCKR and FGF21 genes with circulating FGF21 concentrations. Furthermore, our results support a strong causal effect of FGF21 on improved lipid profile, reduced alcohol consumption and C-reactive protein concentrations, and liver function biomarkers including fibrosis. We found largely null or weak positive associations with fat mass, diabetes, and cardiovascular disease as well as higher insulin-like growth factor-I concentrations, which could indicate a compensatory increase to regulate the above FGF21 resistant states in humans.
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| 9. |
- Petridou, Eleni, et al.
(författare)
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Neonatal leptin levels are strongly associated with female gender, birth length, IGF-I levels and formula feeding.
- 2005
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 62:3, s. 366-71
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate predictors of circulating leptin in healthy full-term newborns and to explore the relationship with anthropometric variables, serum levels of adiponectin and the major components of the IGF system at birth. To explore whether leptin levels are regulated by breastfeeding vs. formula feeding.DESIGN: Observational cross-sectional study.PATIENTS: Three hundred and nineteen healthy full-term newborns delivered during 1999 in Athens, Greece.MEASUREMENTS: Anthropometric measurements, formula feeding information and blood samples were obtained. Leptin and adiponectin determinations were performed using a radioimmunoassay (RIA).RESULTS: Multivariate regression analyses showed that leptin levels were positively associated with female gender, newborn length, ponderal index and IGF-I levels, but not with adiponectin levels. Newborns who were fed exclusively with milk formulas had more than twice the leptin levels of those who were exclusively breastfed.CONCLUSIONS: Leptin levels are positively related to female gender and anthropometric characteristics of neonates but, contrary to studies in adults, are not correlated with adiponectin levels. We also found evidence that formula feeding imparts a considerable increase in leptin levels in newborns.
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| 10. |
- Petridou, Eleni T., et al.
(författare)
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Circulating adiponectin levels and expression of adiponectin receptors in relation to lung cancer : two case-control studies
- 2007
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Ingår i: Oncology. - : S. Karger AG. - 0030-2414 .- 1423-0232. ; 73:3-4, s. 261-269
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Decreased circulating levels of adiponectin, an adipocyte-secreted hormone and endogenous insulin sensitizer, have been associated with several obesity-related malignancies. Thiazolidinedione administration, which increases adiponectin levels, decreases risk for lung cancer. Whether circulating adiponectin levels are associated with lung cancer and/or whether adiponectin receptors are expressed in lung cancer remains unknown. METHODS: We conducted a case-control study of 85 patients with incidental, histologically confirmed lung cancer and 170 healthy controls matched by gender and age. In a separate study, archival lung specimens from 134 cancerous and 8 noncancerous tissues were examined for relative expression of adiponectin receptors AdipoR1 and AdipoR2 using immunohistochemistry. RESULTS: Tobacco smoking, heavy alcohol intake and education were all associated with lung cancer risk, whereas serum adiponectin levels were not significantly different between cases and controls (multiple logistic regression, odds ratio per SD of adiponectin among controls: 1.13, 95% confidence interval: 0.64-2.02). Adiponectin levels were significantly lower (odds ratio: 0.25, 95% confidence interval: 0.10-0.78) among patients with advanced compared to those with limited disease stage. Expression of adiponectin receptors was apparent only in the cancerous lung tissue (64.2% AdipoR1 and 61.9% AdipoR2 in cancerous vs. 0% among noncancerous tissue). Specifically, AdipoR1 was expressed in all disease types, but no difference was noted with disease stage, whereas AdipoR2 was mainly expressed in the non-small cell carcinomas and more prominently in the advanced disease stage (80%). CONCLUSIONS: Circulating adiponectin levels are not different in cases of this malignancy - which seems to be unrelated to obesity and insulin resistance - compared to their healthy controls, though hormonal levels were significantly lower in advanced versus limited lung cancer. Both adiponectin receptors were expressed in cancerous lung tissue, but not in normal control tissue and there was a differential expression by disease stage. These findings should be further explored, especially in the context of the recently reported protective effect of thiazolidinediones in diabetic patients with lung cancer.
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