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Journal of the Society for Gynecologic Investigation
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Ten Polymorphisms of Estrogen-Metabolizing Genes and a Family History of Colon Cancer—An Association Study of Multiple Gene-Gene Interactions

Ambros Huber, MD

Eva-Katrin Bentz, MD

Christian Schneeberger, PhD

Johannes C. Huber, MD, PhD

Lukas Hefler, MD

Departments of Gynecologic Endocrinology and Infertility Treatment, and Gynecology and Obstetrics, Medical University of Vienna, Vienna, Austria

Clemens Tempfer, MD

Departments of Gynecologic Endocrinology and Infertility Treatment, and Gynecology and Obstetrics, Medical University of Vienna, Vienna, Austria; Department of Gynecology and Obstetrics, University of Vienna Medical School, A-1090 Vienna, Währinger Gürtel 18-20, Austria clemens.tempfer{at}meduniwien.ac.at

Estrogen replacement therapy is associated with a reduced risk of colon cancer. Therefore, we evaluated the following ten estrogen metabolism-associated single-nucleotide polymorphisms (SNPs) by sequencing-on-chip technology using solid-phase polymerase chain reaction (PCR) on oligonucleotide microarrays: catechol-O-methyltransferase (COMT) Val158Met G->A, 17-beta-hydroxysteroid dehydrogenase type 1 (HSD17) vlV A->C, cytochrome P-450 (CYP) 17 A2 allele T->C, CYP1A1 MspI RFLP f->C, CYP1A1 Ile462Val A->G, CYP19 Arg264Cys C->T, CYP19 C1558T C->T, CYP 1B1 Leu432Val, CYP1B1 Asn453Ser, and estrogen receptor (ER) alpha IVS1 - 401->C in 76 patients with a family history of colon cancer and 722 healthy controls. Using stepwise logistic regression models, we found that none of the investigated SNPs is associated with a family history of colon cancer in a univariate and multivariate logistic regression model. In addition, when all two-way interactions of the investigated SNPs were ascertained, no significant interactions between SNPs were observed. In conclusion, we found no association between the carriage of one or multiple SNPs of the estrogen metabolism and a family history of colon cancer.

Key Words: Estrogen • gene • polymorphism • microarray • risk factor

Journal of the Society for Gynecologic Investigation, Vol. 12, No. 7, e51-e54 (2005)
DOI: 10.1016/j.jsgi.2005.07.003
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