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Sökning: WFRF:(Kiemeney Lambertus A)

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51.
  • Ros, Martine M., et al. (författare)
  • Fruit and vegetable consumption and risk of aggressive and non-aggressive urothelial cell carcinomas in the European Prospective Investigation into Cancer and Nutrition
  • 2012
  • Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 48:17, s. 3267-3277
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Many epidemiological studies have examined fruit and vegetable consumption in relation to the risk of urothelial cell carcinoma (UCC) of the bladder, but results are inconsistent. The association between fruit and vegetable consumption and UCC risk may vary by bladder tumour aggressiveness. Therefore, we examined the relation between fruit and vegetable consumption and the risk of aggressive and non-aggressive UCC in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: After 8.9 years of follow-up, 947 UCC were diagnosed among 468,656 EPIC participants. Of these, 421 could be classified as aggressive UCC and 433 as non-aggressive UCC cases. At recruitment, fruit and vegetable consumption was assessed by validated dietary questionnaires. Multivariable hazard ratios were estimated using Cox regression stratified by age, sex and center and adjusted for smoking status, duration and intensity of smoking, and energy intake. Results: Total consumption of fruits and vegetables was not associated with aggressive UCC nor with non-aggressive UCC. A 25 g/day increase in leafy vegetables and grapes consumption was associated with a reduced risk of non-aggressive UCC (hazard ratio (HR) 0.88; 95% confidence interval (CI) 0.78-1.00 and HR 0.87; 95% CI 0.77-0.98, respectively), while the intake of root vegetables was inversely associated with risk of aggressive UCC (HR 0.87; 95% CI 0.77-0.98). Conclusion: Our study did not confirm a protective effect of total fruit and/or vegetable consumption on aggressive or non-aggressive UCC. High consumption of certain types of vegetables and of fruits may reduce the risk of aggressive or non-aggressive UCC; however chance findings cannot be excluded. (C) 2012 Elsevier Ltd. All rights reserved.
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52.
  • Styrkarsdottir, Unnur, et al. (författare)
  • Whole-genome sequencing identifies rare genotypes in COMP and CHADL associated with high risk of hip osteoarthritis
  • 2017
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:5, s. 801-805
  • Tidskriftsartikel (refereegranskat)abstract
    • We performed a genome-wide association study of total hip replacements, based on variants identified through whole-genome sequencing, which included 4,657 Icelandic patients and 207,514 population controls. We discovered two rare signals that strongly associate with osteoarthritis total hip replacement: a missense variant, c.1141G>C (p.Asp369His), in the COMP gene (allelic frequency = 0.026%, P = 4.0 × 10-12, odds ratio (OR) = 16.7) and a frameshift mutation, rs532464664 (p.Val330Glyfs∗106), in the CHADL gene that associates through a recessive mode of inheritance (homozygote frequency = 0.15%, P = 4.5 × 10-18, OR = 7.71). On average, c.1141G>C heterozygotes and individuals homozygous for rs532464664 had their hip replacement operation 13.5 years and 4.9 years earlier than others (P = 0.0020 and P = 0.0026), respectively. We show that the full-length CHADL transcript is expressed in cartilage. Furthermore, the premature stop codon introduced by the CHADL frameshift mutation results in nonsense-mediated decay of the mutant transcripts.
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53.
  • Thorgeirsson, Thorgeir E, et al. (författare)
  • A variant associated with nicotine dependence, lung cancer and peripheral arterial disease
  • 2008
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 452:7187, s. 9-638
  • Tidskriftsartikel (refereegranskat)abstract
    • Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year(1,2). Evidence for genetic influence on smoking behaviour and nicotine dependence (ND)(3-8) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health(9,10). Smoking is the major risk factor for lung cancer (LC)(11-14) and is one of the main risk factors for peripheral arterial disease (PAD)(15-17). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking- related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genomewide association study that used low- quantity smokers as controls(18,19), and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene - environment interaction(20), highlighting the role of nicotine addiction in the pathology of other serious diseases.
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54.
  • Zhao, Xiaoyu, et al. (författare)
  • Identification of genetically predicted DNA methylation markers associated with non–small cell lung cancer risk among 34,964 cases and 448,579 controls
  • 2023
  • Ingår i: Cancer. - : John Wiley & Sons. - 0008-543X .- 1097-0142.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Although the associations between genetic variations and lung cancer risk have been explored, the epigenetic consequences of DNA methylation in lung cancer development are largely unknown. Here, the genetically predicted DNA methylation markers associated with non–small cell lung cancer (NSCLC) risk by a two-stage case-control design were investigated.Methods: The genetic prediction models for methylation levels based on genetic and methylation data of 1595 subjects from the Framingham Heart Study were established. The prediction models were applied to a fixed-effect meta-analysis of screening data sets with 27,120 NSCLC cases and 27,355 controls to identify the methylation markers, which were then replicated in independent data sets with 7844 lung cancer cases and 421,224 controls. Also performed was a multi-omics functional annotation for the identified CpGs by integrating genomics, epigenomics, and transcriptomics and investigation of the potential regulation pathways.Results: Of the 29,894 CpG sites passing the quality control, 39 CpGs associated with NSCLC risk (Bonferroni-corrected p ≤ 1.67 × 10−6) were originally identified. Of these, 16 CpGs remained significant in the validation stage (Bonferroni-corrected p ≤ 1.28 × 10−3), including four novel CpGs. Multi-omics functional annotation showed nine of 16 CpGs were potentially functional biomarkers for NSCLC risk. Thirty-five genes within a 1-Mb window of 12 CpGs that might be involved in regulatory pathways of NSCLC risk were identified.Conclusions: Sixteen promising DNA methylation markers associated with NSCLC were identified. Changes of the methylation level at these CpGs might influence the development of NSCLC by regulating the expression of genes nearby.Plain Language Summary: The epigenetic consequences of DNA methylation in lung cancer development are still largely unknown. This study used summary data of large-scale genome-wide association studies to investigate the associations between genetically predicted levels of methylation biomarkers and non–small cell lung cancer risk at the first time. This study looked at how well larotrectinib worked in adult patients with sarcomas caused by TRK fusion proteins. These findings will provide a unique insight into the epigenetic susceptibility mechanisms of lung cancer.
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55.
  • Allen, Naomi E., et al. (författare)
  • Macronutrient intake and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition
  • 2013
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 132:3, s. 635-644
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies have suggested that dietary factors may be important in the development of bladder cancer. We examined macronutrient intake in relation to risk of urothelial cell carcinoma among 469,339 men and women in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by sex, age at recruitment and centre and further adjusted for smoking status and duration, body mass index and total energy intake. After an average of 11.3 years of follow-up, 1,416 new cases of urothelial cell carcinoma were identified. After allowing for measurement error, a 3% increase in the consumption of energy intake from animal protein was associated with a 15% higher risk (95% confidence interval [CI]: 330%; ptrend = 0.01) and a 2% increase in energy from plant protein intake was associated with a 23% lower risk (95% CI: 367%, ptrend = 0.006). Dietary intake of fat, carbohydrate, fibre or calcium was not associated with risk. These findings suggest that animal and/or plant protein may affect the risk of urothelial cell carcinoma, and examination of these associations in other studies is needed.
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56.
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57.
  • Bjerregaard, Bine Kjoller, et al. (författare)
  • Tobacco smoke and bladder cancer-in the European prospective investigation into cancer and nutrition
  • 2006
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 119:10, s. 2412-2416
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of the present study was to investigate the association between smoking and the development of bladder cancer. The study population consisted of 429,906 persons participating in the European Prospective Investigation into Cancer and Nutrition (EPIC), 633 of whom developed bladder cancer during the follow-up period. An increased risk of bladder cancer was found for both current- (incidence rate ratio 3.96, 95% confidence interval: 3.07-5.09) and ex- (2.25, 1.74-2.91) smokers, compared to never-smokers. A positive association with intensity (per 5 cigarettes) was found among current-smokers (1.18, 1.09-1.28). Associations (per 5 years) were observed for duration (1.14, 1.08-1.21), later age at start (0.75, 0.66-0.85) and longer time since quitting (0.92, 0.86-0.98). Exposure to environmental tobacco smoke (ETS) during childhood increased the risk of bladder cancer (1.38, 1.00-1.90), whereas for ETS exposure as adult no effect was detected. The present study confirms the strong association between smoking and bladder cancer. The indication of a higher risk of bladder cancer for those who start smoking at a young age and for those exposed to ETS during childhood adds to the body of evidence suggesting that children are more sensitive to carcinogens than adults. (c) 2006 Wiley-Liss, Inc.
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58.
  • Bosse, Yohan, et al. (författare)
  • Transcriptome-wide association study reveals candidate causal genes for lung cancer
  • 2020
  • Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 146:7, s. 1862-1878
  • Tidskriftsartikel (refereegranskat)abstract
    • We have recently completed the largest GWAS on lung cancer including 29,266 cases and 56,450 controls of European descent. The goal of our study has been to integrate the complete GWAS results with a large‐scale expression quantitative trait loci (eQTL) mapping study in human lung tissues (n = 1,038) to identify candidate causal genes for lung cancer. We performed transcriptome‐wide association study (TWAS) for lung cancer overall, by histology (adenocarcinoma, squamous cell carcinoma and small cell lung cancer) and smoking subgroups (never‐ and ever‐smokers). We performed replication analysis using lung data from the Genotype‐Tissue Expression (GTEx) project. DNA damage assays were performed in human lung fibroblasts for selected TWAS genes. As expected, the main TWAS signal for all histological subtypes and ever‐smokers was on chromosome 15q25. The gene most strongly associated with lung cancer at this locus using the TWAS approach was IREB2 (pTWAS = 1.09E−99), where lower predicted expression increased lung cancer risk. A new lung adenocarcinoma susceptibility locus was revealed on 9p13.3 and associated with higher predicted expression of AQP3 (pTWAS = 3.72E−6). Among the 45 previously described lung cancer GWAS loci, we mapped candidate target gene for 17 of them. The association AQP3‐adenocarcinoma on 9p13.3 was replicated using GTEx (pTWAS = 6.55E−5). Consistent with the effect of risk alleles on gene expression levels, IREB2 knockdown and AQP3 overproduction promote endogenous DNA damage. These findings indicate genes whose expression in lung tissue directly influences lung cancer risk.
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59.
  • Büchner, Frederike L, et al. (författare)
  • Variety in fruit and vegetable consumption and the risk of lung cancer in the European prospective investigation into cancer and nutrition
  • 2010
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 19:9, s. 2278-2286
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: We investigated whether a varied consumption of vegetables and fruits is associated with lower lung cancer risk in the European Prospective Investigation into Cancer and Nutrition study. METHODS: After a mean follow-up of 8.7 years, 1,613 of 452,187 participants with complete information were diagnosed with lung cancer. Diet diversity scores (DDS) were used to quantify the variety in fruit and vegetable consumption. Multivariable proportional hazards models were used to assess the associations between DDS and lung cancer risk. All models were adjusted for smoking behavior and the total consumption of fruit and vegetables. RESULTS: With increasing variety in vegetable subgroups, risk of lung cancer decreases [hazard ratios (HR), 0.77; 95% confidence interval (CI), 0.64-0.94 highest versus lowest quartile; P trend = 0.02]. This inverse association is restricted to current smokers (HR, 0.73; 95% CI, 0.57-0.93 highest versus lowest quartile; P trend = 0.03). In continuous analyses, in current smokers, lower risks were observed for squamous cell carcinomas with more variety in fruit and vegetable products combined (HR/two products, 0.88; 95% CI, 0.82-0.95), vegetable subgroups (HR/subgroup, 0.88; 95% CI, 0.79-0.97), vegetable products (HR/two products, 0.87; 95% CI, 0.79-0.96), and fruit products (HR/two products, 0.84; 95% CI, 0.72-0.97). CONCLUSION: Variety in vegetable consumption was inversely associated with lung cancer risk among current smokers. Risk of squamous cell carcinomas was reduced with increasing variety in fruit and/or vegetable consumption, which was mainly driven by the effect in current smokers. IMPACT: Independent from quantity of consumption, variety in fruit and vegetable consumption may decrease lung cancer risk.
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60.
  • Büchner, Frederike L, et al. (författare)
  • Variety in vegetable and fruit consumption and risk of bladder cancer in the European prospective investigation into cancer and nutrition
  • 2011
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 128:12, s. 2971-2979
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent research does not show an association between fruit and vegetable consumption and bladder cancer risk. None of these studies investigated variety in fruit and vegetable consumption, which may capture different aspects of consumption. We investigated whether a varied consumption of vegetables and fruits is associated with bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Detailed data on food consumption and complete follow-up for cancer incidence were available for 452,185 participants, who were recruited from ten European countries. After a mean follow-up of 8.7 years, 874 participants were diagnosed with bladder cancer. Diet diversity scores (DDSs) were used to quantify the variety in fruit and vegetable consumption. Multivariable Cox proportional hazard models were used to assess the effect of the DDSs on bladder cancer risk. There was no evidence of a statistically significant association between bladder cancer risk and any of the DDSs when these scores were considered as continuous covariates. However, the hazard ratio (HR) for the highest tertile of the DDS for combined fruit and vegetable consumption was marginally significant compared to the lowest (HR = 1.30, 95% confidence interval: 1.00-1.69, p-trend = 0.05). In EPIC, there is no clear association between a varied fruit and vegetable consumption and bladder cancer risk. This finding provides further evidence for the absence of any strong association between fruit and vegetable consumption as measured by a food frequency questionnaire and bladder cancer risk.
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