TY - JOUR
T1 - Estrogen sulfation genes, hormone replacement therapy, and endometrial cancer risk
AU - Rebbeck, Timothy R.
AU - Troxel, Andrea B.
AU - Wang, Yiting
AU - Walker, Amy H.
AU - Panossian, Saarene
AU - Gallagher, Stephen
AU - Shatalova, Ekaterina G.
AU - Blanchard, Rebecca
AU - Bunin, Greta
AU - DeMichele, Angela
AU - Rubin, Stephen C.
AU - Baumgarten, Mona
AU - Berlin, Michelle
AU - Schinnar, Rita
AU - Berlin, Jesse A.
AU - Strom, Brian L.
PY - 2006/9/20
Y1 - 2006/9/20
N2 - Background: Unopposed estrogen replacement therapy is associated with increased risk of endometrial cancer. To investigate the mechanism of this association, we evaluated whether risk of endometrial cancer was associated with the genotypes involved in steroid hormone metabolism and the duration of exogenous hormone use. Methods: A population-based case-control study in nine counties of the Philadelphia metropolitan area was undertaken with 502 case patients with endometrial cancer and 1326 age- and race-matched control subjects. Data regarding exogenous hormone use were obtained by interview, and genotypes of the genes COMT, CYP1A1, CYP1A2, CYP1B1, CYP3A4, PGR, SULT1A1, SULT1E1, and UGT1A1 were obtained by polymerase chain reaction techniques. Conditional logistic regression was used to examine the relationship among genotype, hormone use, and endometrial cancer risk. Results: Associations were observed between the risk of endometrial cancer and genotypes of the following steroid hormone metabolism genes: CYP1A1*2C (adjusted odds ratio [OR] = 1.68, 95% confidence interval [CI] = 1.08 to 2.61); SULT1A1*3 (adjusted OR = 0.51, 95% CI = 0.29 to 0.92); and the G → A variant in the promoter of SULT1E1 at position - 64 (adjusted OR =; 1.45, 95% CI = 1.06 to 1.99). We observed a statistically significant interaction between estrogen replacement therapy use and SULT1A1*2 genotype: the SULT1A1*2 allele and long-term use of estrogen replacement therapy were associated with statistically significantly higher risk of endometrial cancer (adjusted OR = 3.85, 95% CI = 1.48 to 10.00) than that of the SULT1A1*2 allele and no estrogen replacement therapy use. Conclusions: Among women with long-term use of estrogen replacement therapy or combined hormone replacement therapy, the risk of endometrial cancer may be associated with functionally relevant genotypes that regulate steroid hormone sulfation.
AB - Background: Unopposed estrogen replacement therapy is associated with increased risk of endometrial cancer. To investigate the mechanism of this association, we evaluated whether risk of endometrial cancer was associated with the genotypes involved in steroid hormone metabolism and the duration of exogenous hormone use. Methods: A population-based case-control study in nine counties of the Philadelphia metropolitan area was undertaken with 502 case patients with endometrial cancer and 1326 age- and race-matched control subjects. Data regarding exogenous hormone use were obtained by interview, and genotypes of the genes COMT, CYP1A1, CYP1A2, CYP1B1, CYP3A4, PGR, SULT1A1, SULT1E1, and UGT1A1 were obtained by polymerase chain reaction techniques. Conditional logistic regression was used to examine the relationship among genotype, hormone use, and endometrial cancer risk. Results: Associations were observed between the risk of endometrial cancer and genotypes of the following steroid hormone metabolism genes: CYP1A1*2C (adjusted odds ratio [OR] = 1.68, 95% confidence interval [CI] = 1.08 to 2.61); SULT1A1*3 (adjusted OR = 0.51, 95% CI = 0.29 to 0.92); and the G → A variant in the promoter of SULT1E1 at position - 64 (adjusted OR =; 1.45, 95% CI = 1.06 to 1.99). We observed a statistically significant interaction between estrogen replacement therapy use and SULT1A1*2 genotype: the SULT1A1*2 allele and long-term use of estrogen replacement therapy were associated with statistically significantly higher risk of endometrial cancer (adjusted OR = 3.85, 95% CI = 1.48 to 10.00) than that of the SULT1A1*2 allele and no estrogen replacement therapy use. Conclusions: Among women with long-term use of estrogen replacement therapy or combined hormone replacement therapy, the risk of endometrial cancer may be associated with functionally relevant genotypes that regulate steroid hormone sulfation.
UR - http://www.scopus.com/inward/record.url?scp=33749035262&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33749035262&partnerID=8YFLogxK
U2 - 10.1093/jnci/djj360
DO - 10.1093/jnci/djj360
M3 - Article
C2 - 16985250
AN - SCOPUS:33749035262
SN - 0027-8874
VL - 98
SP - 1311
EP - 1320
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 18
ER -