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Search: WFRF:(Butt Julia) > (2020)

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  • Butt, Julia, et al. (author)
  • Antibody Responses to Helicobacter pylori and Risk of Developing Colorectal Cancer in a European Cohort
  • 2020
  • In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 29:7, s. 1475-1481
  • Journal article (peer-reviewed)abstract
    • Background: While Helicobacter pylori (H. pylori) is the major cause of gastric cancer, it has also been suggested to be involved in colorectal cancer development. However, prospective studies addressing H. pylori and colorectal cancer are sparse and inconclusive. We assessed the association of antibody responses to H. pylori proteins with colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.Methods: We applied H. pylori multiplex serology to measure antibody responses to 13 H. pylori proteins in prediagnostic serum samples from 485 colorectal cancer cases and 485 matched controls nested within the EPIC study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable conditional logistic regression to estimate the association of H. pylori overall and protein-specific seropositivity with odds of developing colorectal cancer.Results: Fifty-one percent of colorectal cancer cases were H. pylori seropositive compared with 44% of controls, resulting in an OR of 1.36 (95% CI, 1.00-1.85). Among the 13 individual H. pylori proteins, the association was driven mostly by seropositivity to Helicobacter cysteine-rich protein C (HcpC; OR: 1.66; 95% CI, 1.19-2.30) and Vacuolating cytotoxin A (VacA) (OR: 1.34; 95% CI, 0.99-1.82), the latter being nonstatistically significant only in the fully adjusted model.Conclusions: In this prospective multicenter European study, antibody responses to H. pylori proteins, specifically HcpC and VacA, were associated with an increased risk of developing colorectal cancer. Impact: Biological mechanisms for a potential causal role of H. pylori in colorectal carcinogenesis need to be elucidated, and subsequently whether H. pylori eradication may decrease colorectal cancer incidence.
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2.
  • Butt, Linus, et al. (author)
  • A molecular mechanism explaining albuminuria in kidney disease
  • 2020
  • In: Nature Metabolism. - : Springer Nature. - 2522-5812. ; 2:5, s. 461-474
  • Journal article (peer-reviewed)abstract
    • Mammalian kidneys constantly filter large amounts of liquid, with almost complete retention of albumin and other macromolecules in the plasma. Breakdown of the three-layered renal filtration barrier results in loss of albumin into urine (albuminuria) across the wall of small renal capillaries, and is a leading cause of chronic kidney disease. However, exactly how the renal filter works and why its permeability is altered in kidney diseases is poorly understood. Here we show that the permeability of the renal filter is modulated through compression of the capillary wall. We collect morphometric data prior to and after onset of albuminuria in a mouse model equivalent to a human genetic disease affecting the renal filtration barrier. Combining quantitative analyses with mathematical modelling, we demonstrate that morphological alterations of the glomerular filtration barrier lead to reduced compressive forces that counteract filtration pressure, thereby resulting in capillary dilatation, and ultimately albuminuria. Our results reveal distinct functions of the different layers of the filtration barrier and expand the molecular understanding of defective renal filtration in chronic kidney disease.
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