| 1. |
- Jiang, X., et al.
(författare)
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Shared heritability and functional enrichment across six solid cancers
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
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| 2. |
- Galon, Jerome, et al.
(författare)
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Cancer classification using the Immunoscore : a worldwide task force
- 2012
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Ingår i: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 10, s. 205-
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Forskningsöversikt (refereegranskat)abstract
- Prediction of clinical outcome in cancer is usually achieved by histopathological evaluation of tissue samples obtained during surgical resection of the primary tumor. Traditional tumor staging (AJCC/UICC-TNM classification) summarizes data on tumor burden (T), presence of cancer cells in draining and regional lymph nodes (N) and evidence for metastases (M). However, it is now recognized that clinical outcome can significantly vary among patients within the same stage. The current classification provides limited prognostic information, and does not predict response to therapy. Recent literature has alluded to the importance of the host immune system in controlling tumor progression. Thus, evidence supports the notion to include immunological biomarkers, implemented as a tool for the prediction of prognosis and response to therapy. Accumulating data, collected from large cohorts of human cancers, has demonstrated the impact of immune-classification, which has a prognostic value that may add to the significance of the AJCC/UICC TNM-classification. It is therefore imperative to begin to incorporate the ` Immunoscore' into traditional classification, thus providing an essential prognostic and potentially predictive tool. Introduction of this parameter as a biomarker to classify cancers, as part of routine diagnostic and prognostic assessment of tumors, will facilitate clinical decision-making including rational stratification of patient treatment. Equally, the inherent complexity of quantitative immunohistochemistry, in conjunction with protocol variation across laboratories, analysis of different immune cell types, inconsistent region selection criteria, and variable ways to quantify immune infiltration, all underline the urgent requirement to reach assay harmonization. In an effort to promote the Immunoscore in routine clinical settings, an international task force was initiated. This review represents a follow-up of the announcement of this initiative, and of the J Transl Med. editorial from January 2012. Immunophenotyping of tumors may provide crucial novel prognostic information. The results of this international validation may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune).
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| 3. |
- Oberg, M, et al.
(författare)
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Subchronic toxicity of Baltic herring oil and its fractions in the rat I: Fractionation and levels of organohalogen pollutants
- 2002
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Ingår i: Pharmacology and Toxicology. - : Wiley. - 1600-0773 .- 0901-9928. ; 91:5, s. 220-231
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Tidskriftsartikel (refereegranskat)abstract
- Baltic herring (Clupea harengus) oil was extracted and fractionated. To examine the contribution to toxicity and biological effects of different halogenated organic pollutants, the herring oil and the fractions were mixed into pelleted food and given to Sprague-Dawley female rats at three levels, corresponding to a human intake of 1.6, 8.2 and 34.4 kg fish per week. Herring oil, its fractions, as well as liver tissues from exposed rats, were analyzed for: eight chlorinated biphenyls, all 2,3,7,8-substituted chlorinated dibenzo-p-dioxins and dibenzofurans, hexachlorocyclohexanes, hexachlorobenzene, 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT), DDT-metabolites, three brominated diphenylethers as well as extractable organically bound chlorine and halogenated fatty acids. A bioassay (EROD) was used for measuring the dioxin-like enzyme induction activity. Nordic Sea lodda (Mallotus villosus) oil was used as a nutritionally equivalent control, with much lower levels of halogenated organic pollutants. A full toxicological subchronic examination is reported in the following paper (Stern et al. 2002). In this study, we report that the fractionation procedure resulted in a substantial reduction of most of the pollutants in the triacylglycerol fraction, and a pronounced enrichment of most of the pollutants into the two other fractions. However, all contaminants were present at some levels in all of the fractions. The concentrations of organoltalogens found in this study were representative for Baltic herring during the mid-1990s. Rat liver tissue showed similar residue patterns as the diet, with the exception of chlorinated dibenzo-p-dioxin and dibenzofuran congeners that had a higher liver retention than pesticides, chlorinated biphenyls and brominated diphenylethers.
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