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Association of genetic variations of selenoprotein genes, plasma selenium levels, and prostate cancer aggressiveness at diagnosis

2016; Wiley; Volume: 76; Issue: 7 Linguagem: Inglês

10.1002/pros.23160

1097-0045

Wanling Xie, Ming Yang, June M. Chan, Tong Sun, Lorelei A. Mucci, Kathryn L. Penney, Gwo‐Shu Mary Lee, Philip W. Kantoff,

Glutathione Transferases and Polymorphisms

The ProstateVolume 76, Issue 7 p. 691-699 Original Article Association of genetic variations of selenoprotein genes, plasma selenium levels, and prostate cancer aggressiveness at diagnosis Wanling Xie, Wanling Xie Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MassachusettsSearch for more papers by this authorMing Yang, Ming Yang Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MassachusettsSearch for more papers by this authorJune Chan, June Chan Department of Epidemiology and Biostatistics and Urology, University of California, San Francisco, CaliforniaSearch for more papers by this authorTong Sun, Tong Sun Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MassachusettsSearch for more papers by this authorLorelei A. Mucci, Lorelei A. Mucci Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MassachusettsSearch for more papers by this authorKathryn L. Penney, Kathryn L. Penney Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MassachusettsSearch for more papers by this authorGwo-Shu Mary Lee, Corresponding Author Gwo-Shu Mary Lee Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts Correspondence to: Gwo-Shu Mary Lee, PhD, and Philip W. Kantoff, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215. E-mail: gwo-shu_lee@dfci.harvard.edu (G-S. M. L.); kantoff@mskcc.org (P. W. K.)Search for more papers by this authorPhilip W. Kantoff, Corresponding Author Philip W. Kantoff Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts Correspondence to: Gwo-Shu Mary Lee, PhD, and Philip W. Kantoff, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215. E-mail: gwo-shu_lee@dfci.harvard.edu (G-S. M. L.); kantoff@mskcc.org (P. W. K.)Search for more papers by this author Wanling Xie, Wanling Xie Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MassachusettsSearch for more papers by this authorMing Yang, Ming Yang Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MassachusettsSearch for more papers by this authorJune Chan, June Chan Department of Epidemiology and Biostatistics and Urology, University of California, San Francisco, CaliforniaSearch for more papers by this authorTong Sun, Tong Sun Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MassachusettsSearch for more papers by this authorLorelei A. Mucci, Lorelei A. Mucci Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MassachusettsSearch for more papers by this authorKathryn L. Penney, Kathryn L. Penney Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MassachusettsSearch for more papers by this authorGwo-Shu Mary Lee, Corresponding Author Gwo-Shu Mary Lee Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts Correspondence to: Gwo-Shu Mary Lee, PhD, and Philip W. Kantoff, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215. E-mail: gwo-shu_lee@dfci.harvard.edu (G-S. M. L.); kantoff@mskcc.org (P. W. K.)Search for more papers by this authorPhilip W. Kantoff, Corresponding Author Philip W. Kantoff Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts Correspondence to: Gwo-Shu Mary Lee, PhD, and Philip W. Kantoff, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215. E-mail: gwo-shu_lee@dfci.harvard.edu (G-S. M. L.); kantoff@mskcc.org (P. W. K.)Search for more papers by this author First published: 05 February 2016 https://doi.org/10.1002/pros.23160Citations: 18 Wanling Xie and Ming Yang equally contributed to this work. Conflicts of interest: The authors declare no conflicts of interest. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract BACKGROUND Genetic variations in some of the selenoprotein genes, alone or together with an individual's selenium status, may influence risk or progression of prostate cancer. We investigated the impact of genetic variants of selenoproteins on plasma selenium levels and cancer aggressiveness at diagnosis in men with localized prostate cancer (PCa). METHODS The study cohort comprised 722 patients seen at Dana-Farber Cancer Institute who had localized/locally advanced PCa (i.e., stage T3 or less, N0, and M0) from 1994 to 2001. Fifty-five tagging single nucleotide polymorphisms (SNPs) from six selenoprotein genes (TXNRD1, TXNRD2, SEP15, GPX3, SELENBP1, and SEPP1) were analyzed. Logistic regression is used to examine associations of genotypes and plasma selenium levels with risk of aggressive disease, defined as D'Amico intermediate/high risk categories. Step down permutation was applied to adjust for multiple comparisons. RESULTS Three hundred and forty-eight patients (48%) had aggressive disease at diagnosis. Two SNPs were associated with cancer aggressiveness at diagnosis (unadjusted P = 0.017 and 0.018, respectively). The odds ratio for aggressive disease in patients carrying TXNRD2 rs1005873-AG/GG genotypes or SELENBP1 rs10788804-AG/AA genotypes was 1.54 (95%CI = 1.08, 2.20) and 1.45 (95%CI = 1.07, 1.98), respectively, compared to TXNRD2 rs1005873-AA or SELENBP1 rs10788804-GG carriers. Four SNPs in TXNRD2 (rs1005873, rs13054371, rs3788310, and rs9606174) and the rs230820 in SEPP1 were associated with plasma selenium levels (unadjusted P < 0.05). Permutation adjusted P-values were not statistically significant for all these comparisons at the cut-off point of 0.05. CONCLUSION We identified polymorphisms in selenoproteins that may influence the plasma selenium levels and may be associated with the risk of presenting with aggressive PCa in men with localized or locally advanced PCa. These results should be validated in other independent datasets. Prostate 76:691–699, 2016. © 2016 Wiley Periodicals, Inc. Citing Literature Supporting Information Additional supporting information may be found in the online version of this article at the publisher's web-site. Filename Description pros23160-sup-0001-SuppData-S1.docx64 KB Supporting Information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume76, Issue7May 15, 2016Pages 691-699 RelatedInformation