UDP-glucuronosyltransferase and sulfotransferase polymorphisms, sex hormone concentrations, and tumor receptor status in breast cancer patients

Rachel Sparks, Cornelia M. Ulrich, Jeannette Bigler, Shelley S. Tworoger, Yutaka Yasui, Kumar Rajan, Peggy Porter, Frank Z. Stanczyk, Rachel Ballard-Barbash, Xiaopu Yuan, Ming Gang Lin, Lynda McVarish, Erin J. Aiello, Anne McTiernan

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

Introduction: UDP-glucuronosyltransferase (UGT) and sulfotransferase (SULT) enzymes are involved in removing sex hormones from circulation. Polymorphic variation in five UGT and SULT genes - UGT1A1 ((TA)6/(TA)7), UGT2B4 (Asp458Glu), UGT2B7 (His268Tyr), UGT2B15 (Asp85Tyr), and SULT1A1 (Arg213His) - may be associated with circulating sex hormone concentrations, or the risk of an estrogen receptor-negative (ER-) or progesterone receptor-negative (PR-) tumor. Methods: Logistic regression analysis was used to estimate the odds ratios of an ER- or PR- tumor associated with polymorphisms in the genes listed above for 163 breast cancer patients from a population-based cohort study of women in western Washington. Adjusted geometric mean estradiol, estrone, and testosterone concentrations were calculated within each UGT and SULT genotype for a subpopulation of postmenopausal breast cancer patients not on hormone therapy 2-3 years after diagnosis (n = 89). Results: The variant allele of UGT1A1 was associated with reduced risk of an ER- tumor (P for trend = 0.03), and variants of UGT2B15 and SULT1A1 were associated with non-statistically significant risk reductions. There was some indication that plasma estradiol and testosterone concentrations varied by UGT2B15 and SULT1A1 genotypes; women with the UGT2B15 Asp/Tyr and Tyr/Tyr genotypes had higher concentrations of estradiol than women with the Asp/Asp genotype (P = 0.004). Compared with women with the SULT1A1 Arg/Arg and Arg/His genotypes, women with the His/His genotype had elevated concentrations of testosterone (P = 0.003). Conclusions: The risk of ER- breast cancer tumors may vary by UGT or SULT genotype. Further, plasma estradiol and testosterone concentrations in breast cancer patients may differ depending on some UGT and SULT genotypes.

Original languageEnglish (US)
Article numberR488
JournalBreast Cancer Research
Volume6
Issue number5
DOIs
StatePublished - Jun 29 2004
Externally publishedYes

Keywords

  • Breast cancer
  • Estrogen
  • Glucuronosyltransferase
  • Polymorphism
  • Sulfotransferase
  • Testosterone

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Sparks, R., Ulrich, C. M., Bigler, J., Tworoger, S. S., Yasui, Y., Rajan, K., Porter, P., Stanczyk, F. Z., Ballard-Barbash, R., Yuan, X., Lin, M. G., McVarish, L., Aiello, E. J., & McTiernan, A. (2004). UDP-glucuronosyltransferase and sulfotransferase polymorphisms, sex hormone concentrations, and tumor receptor status in breast cancer patients. Breast Cancer Research, 6(5), [R488]. https://doi.org/10.1186/bcr818