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| Research article summary (published 29 Nov 2009): |
Common germline polymorphisms in COMT, CYP19A1, ESR1, PGR, SULT1E1 and STS and survival after a diagnosis of breast cancer.
Full Abstract
Although preliminary evidence suggests that germline variation in genes involved in steroid hormone metabolism may alter breast cancer prognosis, this has not been systematically evaluated. We examined associations between germline polymorphisms in 6 genes involved in the steroid hormone metabolism and signaling pathway (COMT, CYP19A1, ESR1, PGR, SULT1E1, STS) and survival among women with breast cancer participating in SEARCH, a population-based case-control study. Blood samples from up to 4,470 women were genotyped for 4 possible functional SNPs in CYP19A1 and 106 SNPs tagging the common variation in the remainder of the genes. The genotypes of each polymorphism were tested for association with survival after breast cancer diagnosis using Cox regression analysis. Significant evidence of an association was observed for a COMT polymorphism (rs4818 p = 0.016) under the codominant model. This SNP appeared to fit a dominant model better (HR = 0.80 95% CI: 0.69-0.95, p = 0.009); however, the result was only marginally significant after permutation analysis adjustment for multiple hypothesis tests (p = 0.047). To further evaluate this finding, somatic expression microarray data from 8 publicly available datasets were used to test the association between survival and tumor COMT gene expression; no statistically significant associations were observed. A correlated SNP in COMT, rs4860, has recently been associated with breast cancer prognosis in Chinese women in a dominant model. These results suggest that COMT rs4818, or a variant it tags, is associated with breast cancer prognosis. Further study of COMT and its putative association with breast cancer prognosis is warranted.
Author information
Author/s: Udler, Miriam S (MS); Azzato, Elizabeth M (EM); Healey, Catherine S (CS); Ahmed, Shahana (S); Pooley, Karen A (KA); Greenberg, David (D); Shah, Mitul (M); Teschendorff, Andrew E (AE); Caldas, Carlos (C); Dunning, Alison M (AM); Ostrander, Elaine A (EA); Caporaso, Neil E (NE); Easton, Douglas (D); Pharoah, Paul D (PD);
Affiliation: Strangeways Research Laboratory, Departments of Public Health and Primary Care and Oncology, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, United Kingdom.
Grants: (Agency:Cancer Research UK)
Journal and publication information
Publication Type: Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't
Journal: International journal of cancer. Journal international du cancer (Int J Cancer), published in United States. (Language: eng)
Reference: 2009-Dec; vol 125 (issue 11) : pp 2687-96
Dates: Created 2009/10/05; Completed 2009/11/06;
PMID: 19551860, status: MEDLINE (last retrieval date: 11/6/2009, IMS Date: )
Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.
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