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

Breast Cancer Research

Anne McTiernan¹  Erin J Aiello³  Lynda McVarish⁵  Ming Gang Lin⁵  Xiaopu Yuan⁵  Rachel Ballard-Barbash⁴  Frank Z Stanczyk²  Peggy Porter⁵  Kumar B Rajan⁵  Yutaka Yasui⁵  Shelley S Tworoger¹  Jeannette Bigler⁵  Cornelia M Ulrich¹  Rachel Sparks¹ 

[1] Department of Epidemiology, University of Washington, Seattle, Washington, USA;University of Southern California, Los Angeles, California, USA;Group Health Cooperative, Center for Health Studies, Seattle, Washington, USA;Applied Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland, USA;Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

关键词: testosterone;    sulfotransferase;    polymorphism;    glucuronosyltransferase;    estrogen;    breast cancer;   

Others  :  1118731
DOI  :  10.1186/bcr818

 received in 2003-11-19, accepted in 2004-05-20,  发布年份 2004

【 摘 要 】

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.

【 授权许可】

   
2004 Sparks et al.; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

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