Genetic variations in UGT1A1 and UGT2B7 and endometrial cancer risk.
Uridine diphosphate-glucuronosyltransferases (UGTs) are a family of phase II-metabolizing enzymes involved in glucuronic acid conjugation of sex steroid hormones. UGT1A1 and UGT2B7 are expressed in the uterus and involved in the conjugation and elimination of estrogens. Chronic exposure to estrogens is associated with endometrial cancer. Functional polymorphisms have been identified in UGT1A1 and UGT2B7. We hypothesized that these variants may be associated with endometrial cancer risk. We conducted a case-control study nested within the Nurses' Health Study and the Women's Health Study to investigate the associations between five polymorphisms and endometrial cancer risk using 593 invasive endometrial cancer cases and 1545 controls. We did observe the suggestion of an inverse association with homozygote variant carriers of UGT1A1*28 and endometrial cancer risk. We did not observe significant associations between individual single nucleotide polymorphisms and UGT1A1 haplotypes and endometrial cancer risk. Our data suggest that these UGT polymorphisms do not contribute significantly to endometrial cancer risk.
McGrath
Monica
M
Department of Epidemiology, Harvard School of Public Health, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. monica.mcgrath@channing.havard.edu
Lepine
Johanie
J
Lee
I-Min
IM
Villeneuve
Lyne
L
Buring
Julie
J
Guillemette
Chantal
C
De Vivo
Immaculata
I
D016022:Case-Control Studies; D015331:Cohort Studies; D016889:Endometrial Neoplasms / Q000201:enzymology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D000099148:UGT1A1 Enzyme
D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme; C491474:UGT2B7 protein, human