Associations between the CYP17, CYPIB1, COMT and SHBG polymorphisms and serum sex hormones in post-menopausal breast cancer survivors |
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Authors: | Page E. Abrahamson Shelley S. Tworoger Erin J. Aiello Leslie Bernstein Cornelia M. Ulrich Frank D. Gilliland Frank Z. Stanczyk Richard Baumgartner Kathy Baumgartner Bess Sorensen Rachel Ballard-Barbash Anne McTiernan |
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Affiliation: | (1) Cancer Prevention Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M4-B402, Seattle, WA 98109-1024, USA;(2) Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA, USA;(3) Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA;(4) Group Health Center for Health Studies, Seattle, WA, USA;(5) Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA;(6) Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA;(7) Department of Epidemiology and Clinical Investigation Science, University of Louisville, Louisville, KY, USA;(8) Applied Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD, USA |
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Abstract: | Several polymorphisms have been identified in genes that code for enzymes involved with estrogen biosynthesis and metabolism. Little is known about the functional relevance of these polymorphisms on sex hormones in vivo. We examined the association between CYP17, CYP1B1, COMT or SHBG genotypes and serum concentrations of estrone, estradiol, free estradiol, sex hormone-binding globulin (SHBG), testosterone, free testosterone and dehyroepiandrosterone in 366 post-menopausal breast cancer survivors in New Mexico, California and Washington. Hormone levels were determined by high performance liquid chromatography and radioimmunoassay in blood drawn approximately 2 years post-diagnosis. We used generalized linear regression to calculate mean hormone levels by genotype, adjusting for age, race/ethnicity, stage, study site, tamoxifen use, number of remaining ovaries, hormone therapy use, marital status and BMI. No associations were observed between any of the genotypes and sex hormones when analyzing the main effects. In subgroup analyses, androgen levels of Hispanic women with the variant (A2) CYP17 genotype were 46–87% higher than those of women with the wild-type; androgen levels were 13–20% lower in non-Hispanic whites with the variant genotype; no difference by genotype was observed for African-American women. Current tamoxifen users with the variant asn327 SHBG genotype had 81% higher serum SHBG and 39% lower free testosterone concentrations than women with the wild-type genotype. Non-tamoxifen users with the variant SHBG allele had elevated free estradiol levels. These results provide little evidence that the CYP17, CYP1B1, and COMT polymorphisms are associated with different sex hormone levels in post-menopausal breast cancer survivors. |
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Keywords: | Breast cancer COMT CYP17 CYP1B1 Estrogen SHBG Testosterone |
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