UDP-glucuronosyltransferase and sulfotransferase polymorphisms, sex hormone concentrations, and tumor receptor status in breast cancer patients.
BACKGROUND
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.
Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. rsparks@fhcrc.org
Rachel
R
Sparks
Cornelia M
CM
Ulrich
Jeannette
J
Bigler
Shelley S
SS
Tworoger
Yutaka
Y
Yasui
Kumar B
KB
Rajan
Peggy
P
Porter
Frank Z
FZ
Stanczyk
Rachel
R
Ballard-Barbash
Xiaopu
X
Yuan
Ming Gang
MG
Lin
Lynda
L
McVarish
Erin J
EJ
Aiello
Anne
A
McTiernan
D000328:Adult; D000368:Aged; D015239:Arylsulfotransferase / Q000235:genetics; D044466:Asian People; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D004958:Estradiol / Q000097:blood; D004970:Estrone / Q000097:blood; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012044:Regression Analysis; D012307:Risk Factors; D015238:Sulfotransferases / Q000235:genetics*; D013739:Testosterone / Q000097:blood; D044465:White People / Q000235:genetics; D000099148:UGT1A1 Enzyme
D015239:Arylsulfotransferase; D004958:Estradiol; D004970:Estrone; D014453:Glucuronosyltransferase; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D015238:Sulfotransferases; D013739:Testosterone; D000099148:UGT1A1 Enzyme; C113480:UGT2B11 protein, human; C491474:UGT2B7 protein, human; C472000:UDP-glucuronosyltransferase 2B15, human; C117544:SULT1A1 protein, human