Germline Genetic Variation, Cancer Outcome, and Pharmacogenetics
Publication: Journal of Clinical Oncology
Abstract
Studies of the role of germline or inherited genetic variation on cancer outcome can fall into three distinct categories. First, the impact of highly penetrant but lowly prevalent mutations of germline DNA on cancer prognosis has been studied extensively for BRCA1 and BRCA2 mutations as well as mutations related to hereditary nonpolyposis colorectal cancer syndrome. These mainly modest-sized analyses have produced conflicting results. Although some associations have been observed, they may not be independent of other known clinical or molecular prognostic factors. Second, the impact of germline polymorphisms on cancer prognosis is a burgeoning field of research. However, a deeper understanding of potentially confounding somatic changes and larger multi-institutional, multistage studies may be needed before consistent results are seen. Third, research examining the impact of germline genetic variation on differential treatment response or toxicity (pharmacogenetics) has produced some proof-of-principle results. Putative germline pharmacogenetic predictors of outcome include DPYD polymorphisms and fluorouracil toxicity, UGT1A1 variation and irinotecan toxicity, and CYP2D6 polymorphisms and tamoxifen efficacy, with emerging data on predictors of molecularly targeted or biologic drugs. Here we review data pertaining to these germline outcome and germline toxicity relationships.
Get full access to this article
View all available purchase options and get full access to this article.
Authors' Disclosures of Potential Conflicts of Interest
The author(s) indicated no potential conflicts of interest.
Information & Authors
Information
Published In
Copyright
© 2010 by American Society of Clinical Oncology.
History
Published online: August 02, 2010
Published in print: September 10, 2010
Authors
Author Contributions
Conception and design: Linda Coate, David Christiani, Geoffrey Liu
Collection and assembly of data: Linda Coate, Sinead Cuffe
Data analysis and interpretation: Linda Coate, Sinead Cuffe, Anne Horgan, Geoffrey Liu
Manuscript writing: Linda Coate, Rayjean J. Hung, David Christiani, Geoffrey Liu
Final approval of manuscript: Linda Coate, Sinead Cuffe, Anne Horgan, Rayjean J. Hung, David Christiani, Geoffrey Liu
Funding Information
Supported in part by the Alan B. Brown Chair in Molecular Genomics and Cancer Care Ontario Research Chair in Experimental Therapeutics and Population Studies (G.L.), operating grants from the Ontario Institute for Cancer Research, and the Posluns Family Foundation, Toronto, Ontario, Canada.
Metrics & Citations
Metrics
Altmetric
Citations
Article Citation
Germline Genetic Variation, Cancer Outcome, and Pharmacogenetics. JCO 28, 4029-4037(2010).
Download Citation
If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download.
For more information or tips please see 'Downloading to a citation manager' in the Help menu.
Download article citation data for:
Journal of Clinical Oncology 2010 28:26, 4029-4037
Journal of Clinical Oncology 2010 28:26, 4029-4037
View Options
Get Access
Login options
Check if you have access through your login credentials or your institution to get full access on this article.
Personal login Institutional LoginPurchase Options
Purchase this article to get full access to it.
Subscribe
Subscribe to this Journal
Renew Your Subscription
Become a Member