| 21. |
- Ding, Li, et al.
(författare)
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Somatic mutations affect key pathways in lung adenocarcinoma
- 2008
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 455:7216, s. 1069-1075
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Tidskriftsartikel (refereegranskat)abstract
- Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.
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| 22. |
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| 25. |
- Assi, N., et al.
(författare)
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A treelet transform analysis to relate nutrient patterns to the risk of hormonal receptor-defined breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2016
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Ingår i: Public Health Nutrition. - 1368-9800 .- 1475-2727. ; 19:2, s. 242-254
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Tidskriftsartikel (refereegranskat)abstract
- Copyright © The Authors 2015 Objective: Pattern analysis has emerged as a tool to depict the role of multiple nutrients/foods in relation to health outcomes. The present study aimed at extracting nutrient patterns with respect to breast cancer (BC) aetiology. Design: Nutrient patterns were derived with treelet transform (TT) and related to BC risk. TT was applied to twenty-three log-transformed nutrient densities from dietary questionnaires. Hazard ratios (HR) and 95 % confidence intervals computed using Cox proportional hazards models quantified the association between quintiles of nutrient pattern scores and risk of overall BC, and by hormonal receptor and menopausal status. Principal component analysis was applied for comparison. Setting: The European Prospective Investigation into Cancer and Nutrition (EPIC). Subjects: Women (n 334 850) from the EPIC study. Results: The first TT component (TC1) highlighted a pattern rich in nutrients found in animal foods loading on cholesterol, protein, retinol, vitamins B12 and D, while the second TT component (TC2) reflected a diet rich in β-carotene, riboflavin, thiamin, vitamins C and B6, fibre, Fe, Ca, K, Mg, P and folate. While TC1 was not associated with BC risk, TC2 was inversely associated with BC risk overall (HRQ5 v. Q1=0·89, 95 % CI 0·83, 0·95, P trend<0·01) and showed a significantly lower risk in oestrogen receptor-positive (HRQ5 v. Q1=0·89, 95 % CI 0·81, 0·98, P trend=0·02) and progesterone receptor-positive tumours (HRQ5 v. Q1=0·87, 95 % CI 0·77, 0·98, P trend<0·01). Conclusions: TT produces readily interpretable sparse components explaining similar amounts of variation as principal component analysis. Our results suggest that participants with a nutrient pattern high in micronutrients found in vegetables, fruits and cereals had a lower risk of BC.
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| 26. |
- Berndt, Sonja, I, et al.
(författare)
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Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes
- 2022
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Ingår i: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 36:12, s. 2835-2844
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Tidskriftsartikel (refereegranskat)abstract
- Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.
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| 27. |
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| 29. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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