Estrogen sulfation genes, hormone replacement therapy, and endometrial cancer risk

Timothy R. Rebbeck, Andrea B. Troxel, Yiting Wang, Amy H. Walker, Saarene Panossian, Stephen Gallagher, Ekaterina G. Shatalova, Rebecca Blanchard, Greta Bunin, Angela DeMichele, Stephen C. Rubin, Mona Baumgarten, Michelle Berlin, Rita Schinnar, Jesse A. Berlin, Brian L. Strom

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1311-1320
Number of pages10
JournalJournal of the National Cancer Institute
Volume98
Issue number18
DOIs
StatePublished - Sep 20 2006
Externally publishedYes

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Hormone Replacement Therapy
Endometrial Neoplasms
Estrogen Replacement Therapy
Estrogens
Genotype
Hormones
Genes
Odds Ratio
Confidence Intervals
Cytochrome P-450 CYP1A1
Steroids
Alleles
Cytochrome P-450 CYP3A
Cytochrome P-450 CYP1A2
Case-Control Studies
Logistic Models
Interviews
Polymerase Chain Reaction
Population

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Rebbeck, T. R., Troxel, A. B., Wang, Y., Walker, A. H., Panossian, S., Gallagher, S., ... Strom, B. L. (2006). Estrogen sulfation genes, hormone replacement therapy, and endometrial cancer risk. Journal of the National Cancer Institute, 98(18), 1311-1320. https://doi.org/10.1093/jnci/djj360

Estrogen sulfation genes, hormone replacement therapy, and endometrial cancer risk. / Rebbeck, Timothy R.; Troxel, Andrea B.; Wang, Yiting; Walker, Amy H.; Panossian, Saarene; Gallagher, Stephen; Shatalova, Ekaterina G.; Blanchard, Rebecca; Bunin, Greta; DeMichele, Angela; Rubin, Stephen C.; Baumgarten, Mona; Berlin, Michelle; Schinnar, Rita; Berlin, Jesse A.; Strom, Brian L.

In: Journal of the National Cancer Institute, Vol. 98, No. 18, 20.09.2006, p. 1311-1320.

Research output: Contribution to journalArticle

Rebbeck, TR, Troxel, AB, Wang, Y, Walker, AH, Panossian, S, Gallagher, S, Shatalova, EG, Blanchard, R, Bunin, G, DeMichele, A, Rubin, SC, Baumgarten, M, Berlin, M, Schinnar, R, Berlin, JA & Strom, BL 2006, 'Estrogen sulfation genes, hormone replacement therapy, and endometrial cancer risk', Journal of the National Cancer Institute, vol. 98, no. 18, pp. 1311-1320. https://doi.org/10.1093/jnci/djj360
Rebbeck TR, Troxel AB, Wang Y, Walker AH, Panossian S, Gallagher S et al. Estrogen sulfation genes, hormone replacement therapy, and endometrial cancer risk. Journal of the National Cancer Institute. 2006 Sep 20;98(18):1311-1320. https://doi.org/10.1093/jnci/djj360
Rebbeck, Timothy R. ; Troxel, Andrea B. ; Wang, Yiting ; Walker, Amy H. ; Panossian, Saarene ; Gallagher, Stephen ; Shatalova, Ekaterina G. ; Blanchard, Rebecca ; Bunin, Greta ; DeMichele, Angela ; Rubin, Stephen C. ; Baumgarten, Mona ; Berlin, Michelle ; Schinnar, Rita ; Berlin, Jesse A. ; Strom, Brian L. / Estrogen sulfation genes, hormone replacement therapy, and endometrial cancer risk. In: Journal of the National Cancer Institute. 2006 ; Vol. 98, No. 18. pp. 1311-1320.
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abstract = "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.",
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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.

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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.

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