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Sökning: WFRF:(Czene Kamila) > (2010-2014) > Multi-Variant Pathw...
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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 04499naa a2200529 4500 | |
| 001 | oai:DiVA.org:uu-135592 | |
| 003 | SwePub | |
| 008 | 101207s2010 | |||||||||||000 ||eng| | |
| 009 | oai:prod.swepub.kib.ki.se:121099666 | |
| 024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1355922 URI |
| 024 | 7 | a https://doi.org/10.1371/journal.pgen.10010122 DOI |
| 024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1210996662 URI |
| 040 | a (SwePub)uud (SwePub)ki | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Low, Yen Ling4 aut |
| 245 | 1 0 | a Multi-Variant Pathway Association Analysis Reveals the Importance of Genetic Determinants of Estrogen Metabolism in Breast and Endometrial Cancer Susceptibility |
| 264 | c 2010-07-01 | |
| 264 | 1 | b Public Library of Science (PLoS),c 2010 |
| 338 | a print2 rdacarrier | |
| 520 | a Despite the central role of estrogen exposure in breast and endometrial cancer development and numerous studies of genes in the estrogen metabolic pathway, polymorphisms within the pathway have not been consistently associated with these cancers. We posit that this is due to the complexity of multiple weak genetic effects within the metabolic pathway that can only be effectively detected through multi-variant analysis. We conducted a comprehensive association analysis of the estrogen metabolic pathway by interrogating 239 tagSNPs within 35 genes of the pathway in three tumor samples. The discovery sample consisted of 1,596 breast cancer cases, 719 endometrial cancer cases, and 1,730 controls from Sweden; and the validation sample included 2,245 breast cancer cases and 1,287 controls from Finland. We performed admixture maximum likelihood (AML)-based global tests to evaluate the cumulative effect from multiple SNPs within the whole metabolic pathway and three sub-pathways for androgen synthesis, androgen-to-estrogen conversion, and estrogen removal. In the discovery sample, although no single polymorphism was significant after correction for multiple testing, the pathway-based AML global test suggested association with both breast (rho(global) = 0.034) and endometrial (rho(global) = 0.052) cancers. Further testing revealed the association to be focused on polymorphisms within the androgen-to-estrogen conversion sub-pathway, for both breast (rho(global) = 0.008) and endometrial cancer (rho(global) = 0.014). The sub-pathway association was validated in the Finnish sample of breast cancer (rho(global) = 0.015). Further tumor subtype analysis demonstrated that the association of the androgen-to-estrogen conversion sub-pathway was confined to postmenopausal women with sporadic estrogen receptor positive tumors (rho(global) = 0.0003). Gene-based AML analysis suggested CYP19A1 and UGT2B4 to be the major players within the sub-pathway. Our study indicates that the composite genetic determinants related to the androgen-estrogen conversion are important for the induction of two hormone-associated cancers, particularly for the hormone-driven breast tumour subtypes. | |
| 653 | a MEDICINE | |
| 653 | a MEDICIN | |
| 700 | 1 | a Li, Yuqing4 aut |
| 700 | 1 | a Humphreys, Keithu Karolinska Institutet4 aut |
| 700 | 1 | a Thalamuthu, Anbupalam4 aut |
| 700 | 1 | a Li, Yi4 aut |
| 700 | 1 | a Darabi, Hatefu Karolinska Institutet4 aut |
| 700 | 1 | a Wedrén, Sara4 aut |
| 700 | 1 | a Bonnard, Carine4 aut |
| 700 | 1 | a Czene, Kamilau Karolinska Institutet4 aut |
| 700 | 1 | a Iles, Mark M.4 aut |
| 700 | 1 | a Heikkinen, Tuomas4 aut |
| 700 | 1 | a Aittomäki, Kristiina4 aut |
| 700 | 1 | a Blomqvist, Carlu Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi4 aut0 (Swepub:uu)carlblom |
| 700 | 1 | a Nevanlinna, Heli4 aut |
| 700 | 1 | a Hall, Peru Karolinska Institutet4 aut |
| 700 | 1 | a Liu, Edison T.4 aut |
| 700 | 1 | a Liu, Jianjun4 aut |
| 710 | 2 | a Karolinska Institutetb Institutionen för onkologi, radiologi och klinisk immunologi4 org |
| 773 | 0 | t PLoS geneticsd : Public Library of Science (PLoS)g 6:7, s. e1001012-q 6:7<e1001012-x 1553-7390x 1553-7404 |
| 856 | 4 | u https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1001012&type=printable |
| 856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-135592 |
| 856 | 4 8 | u https://doi.org/10.1371/journal.pgen.1001012 |
| 856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:121099666 |
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