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Screening for Deleterious Nonsynonymous Single-Nucleotide Polymorphisms in Genes Involved in Steroid Hormone Metabolism and Response

¹ Program in Epidemiology, Fred Hutchinson Cancer Research Center and ² Department of Epidemiology, University of Washington, Seattle, Washington

Requests for reprints: Chu Chen, Program in Epidemiology, Fred Hutchinson Cancer Research Center, P.O. Box 19024, Mailstop M5-C800, 1100 Fairview Avenue North, Seattle, WA 98109-1024. Phone: 206-667-6644; Fax: 206-667-2537. E-mail: cchen{at}fhcrc.org

To facilitate selection of single-nucleotide polymorphisms (SNP) for molecular epidemiologic studies investigating the hormonal carcinogenesis hypothesis, we used two sequence homology–based tools [Sort Intolerant from Tolerant (SIFT) and Polymorphism Phenotype (PolyPhen)] to predict the potential impact a nonsynonymous SNP (nsSNP), which results in an amino acid substitution, may have on the activity of proteins encoded by genes involved in the steroid hormone metabolism and response pathway. We screened 137 variants. Of these, 28% were predicted by SIFT and PolyPhen as having a potentially damaging effect on protein function. Investigation into the association of these variant alleles with hormone-related cancers may prove to be fruitful.

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