Progesterone receptor variant increases ovarian cancer risk in BRCA1 and BRCA2 mutation carriers who were never exposed to oral contraceptives

I. B. Runnebaum, S. Wang-Gohrke, D. Vesprini, R. Kreienberg, Henry T. Lynch, R. Moslehi, P. Ghadirian, B. Weber, A. K. Godwin, H. Risch, J. Garber, C. Lerman, O. I. Olopade, W. D. Foulkes, B. Karlan, E. Warner, B. Rosen, T. Rebbeck, P. Tonin, M. P. Dubé & 2 others D. G. Kieback, S. A. Narod

Research output: Contribution to journalArticle

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Abstract

Oral contraceptives have been shown to be protective against hereditary ovarian cancer. The variant progesterone receptor allele named PROGINS is characterized by an Alu insertion into intron G and two additional mutations in exons 4 and 5. The PROGINS allele codes for a progesterone receptor with increased stability and increased hormone-induced transcriptional activity. We studied the role of the PROGINS allele as a modifying gene in hereditary breast and ovarian cancer. The study included 195 BRCA1 and BRCA2 carriers with a prior diagnosis of ovarian cancer, 392 carriers with a diagnosis of breast cancer and 249 carriers with neither cancer. Fifty-eight women had both forms of cancer. Five hundred and ninety-five women had a BRCA1 mutation and 183 women had a BRCA2 mutation. Overall, there was no association between disease status and the presence of the PROGINS allele. Information on oral contraception use was available for 663 of the 778 carriers of BRCA1 or BRCA2 mutations. Among the 449 subjects with a history of oral contraceptive use (74 cases and 365 controls), no modifying effect of PROGINS was observed [odds ratio (OR) 0.8; 95% confidence interval (CI) 0.5-1.3]. Among the 214 carriers with no past exposure to oral contraceptives, the presence of one or more PROGINS alleles was associated with an OR of 2.4 for ovarian cancer, compared to women without ovarian cancer and with no PROGINS allele (P=0.004; 95% CI 1.4-4.3). The association was present after adjustment for ethnic group and for year of birth.

Original languageEnglish
Pages (from-to)635-638
Number of pages4
JournalPharmacogenetics
Volume11
Issue number7
DOIs
StatePublished - 2001
Externally publishedYes

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Progesterone Receptors
Oral Contraceptives
Ovarian Neoplasms
Alleles
Mutation
Odds Ratio
Confidence Intervals
Breast Neoplasms
Contraception
Ethnic Groups
Introns
Exons
Neoplasms
Parturition
Hormones
Genes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Progesterone receptor variant increases ovarian cancer risk in BRCA1 and BRCA2 mutation carriers who were never exposed to oral contraceptives. / Runnebaum, I. B.; Wang-Gohrke, S.; Vesprini, D.; Kreienberg, R.; Lynch, Henry T.; Moslehi, R.; Ghadirian, P.; Weber, B.; Godwin, A. K.; Risch, H.; Garber, J.; Lerman, C.; Olopade, O. I.; Foulkes, W. D.; Karlan, B.; Warner, E.; Rosen, B.; Rebbeck, T.; Tonin, P.; Dubé, M. P.; Kieback, D. G.; Narod, S. A.

In: Pharmacogenetics, Vol. 11, No. 7, 2001, p. 635-638.

Research output: Contribution to journalArticle

Runnebaum, IB, Wang-Gohrke, S, Vesprini, D, Kreienberg, R, Lynch, HT, Moslehi, R, Ghadirian, P, Weber, B, Godwin, AK, Risch, H, Garber, J, Lerman, C, Olopade, OI, Foulkes, WD, Karlan, B, Warner, E, Rosen, B, Rebbeck, T, Tonin, P, Dubé, MP, Kieback, DG & Narod, SA 2001, 'Progesterone receptor variant increases ovarian cancer risk in BRCA1 and BRCA2 mutation carriers who were never exposed to oral contraceptives', Pharmacogenetics, vol. 11, no. 7, pp. 635-638. https://doi.org/10.1097/00008571-200110000-00010
Runnebaum, I. B. ; Wang-Gohrke, S. ; Vesprini, D. ; Kreienberg, R. ; Lynch, Henry T. ; Moslehi, R. ; Ghadirian, P. ; Weber, B. ; Godwin, A. K. ; Risch, H. ; Garber, J. ; Lerman, C. ; Olopade, O. I. ; Foulkes, W. D. ; Karlan, B. ; Warner, E. ; Rosen, B. ; Rebbeck, T. ; Tonin, P. ; Dubé, M. P. ; Kieback, D. G. ; Narod, S. A. / Progesterone receptor variant increases ovarian cancer risk in BRCA1 and BRCA2 mutation carriers who were never exposed to oral contraceptives. In: Pharmacogenetics. 2001 ; Vol. 11, No. 7. pp. 635-638.
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abstract = "Oral contraceptives have been shown to be protective against hereditary ovarian cancer. The variant progesterone receptor allele named PROGINS is characterized by an Alu insertion into intron G and two additional mutations in exons 4 and 5. The PROGINS allele codes for a progesterone receptor with increased stability and increased hormone-induced transcriptional activity. We studied the role of the PROGINS allele as a modifying gene in hereditary breast and ovarian cancer. The study included 195 BRCA1 and BRCA2 carriers with a prior diagnosis of ovarian cancer, 392 carriers with a diagnosis of breast cancer and 249 carriers with neither cancer. Fifty-eight women had both forms of cancer. Five hundred and ninety-five women had a BRCA1 mutation and 183 women had a BRCA2 mutation. Overall, there was no association between disease status and the presence of the PROGINS allele. Information on oral contraception use was available for 663 of the 778 carriers of BRCA1 or BRCA2 mutations. Among the 449 subjects with a history of oral contraceptive use (74 cases and 365 controls), no modifying effect of PROGINS was observed [odds ratio (OR) 0.8; 95{\%} confidence interval (CI) 0.5-1.3]. Among the 214 carriers with no past exposure to oral contraceptives, the presence of one or more PROGINS alleles was associated with an OR of 2.4 for ovarian cancer, compared to women without ovarian cancer and with no PROGINS allele (P=0.004; 95{\%} CI 1.4-4.3). The association was present after adjustment for ethnic group and for year of birth.",
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T1 - Progesterone receptor variant increases ovarian cancer risk in BRCA1 and BRCA2 mutation carriers who were never exposed to oral contraceptives

AU - Runnebaum, I. B.

AU - Wang-Gohrke, S.

AU - Vesprini, D.

AU - Kreienberg, R.

AU - Lynch, Henry T.

AU - Moslehi, R.

AU - Ghadirian, P.

AU - Weber, B.

AU - Godwin, A. K.

AU - Risch, H.

AU - Garber, J.

AU - Lerman, C.

AU - Olopade, O. I.

AU - Foulkes, W. D.

AU - Karlan, B.

AU - Warner, E.

AU - Rosen, B.

AU - Rebbeck, T.

AU - Tonin, P.

AU - Dubé, M. P.

AU - Kieback, D. G.

AU - Narod, S. A.

PY - 2001

Y1 - 2001

N2 - Oral contraceptives have been shown to be protective against hereditary ovarian cancer. The variant progesterone receptor allele named PROGINS is characterized by an Alu insertion into intron G and two additional mutations in exons 4 and 5. The PROGINS allele codes for a progesterone receptor with increased stability and increased hormone-induced transcriptional activity. We studied the role of the PROGINS allele as a modifying gene in hereditary breast and ovarian cancer. The study included 195 BRCA1 and BRCA2 carriers with a prior diagnosis of ovarian cancer, 392 carriers with a diagnosis of breast cancer and 249 carriers with neither cancer. Fifty-eight women had both forms of cancer. Five hundred and ninety-five women had a BRCA1 mutation and 183 women had a BRCA2 mutation. Overall, there was no association between disease status and the presence of the PROGINS allele. Information on oral contraception use was available for 663 of the 778 carriers of BRCA1 or BRCA2 mutations. Among the 449 subjects with a history of oral contraceptive use (74 cases and 365 controls), no modifying effect of PROGINS was observed [odds ratio (OR) 0.8; 95% confidence interval (CI) 0.5-1.3]. Among the 214 carriers with no past exposure to oral contraceptives, the presence of one or more PROGINS alleles was associated with an OR of 2.4 for ovarian cancer, compared to women without ovarian cancer and with no PROGINS allele (P=0.004; 95% CI 1.4-4.3). The association was present after adjustment for ethnic group and for year of birth.

AB - Oral contraceptives have been shown to be protective against hereditary ovarian cancer. The variant progesterone receptor allele named PROGINS is characterized by an Alu insertion into intron G and two additional mutations in exons 4 and 5. The PROGINS allele codes for a progesterone receptor with increased stability and increased hormone-induced transcriptional activity. We studied the role of the PROGINS allele as a modifying gene in hereditary breast and ovarian cancer. The study included 195 BRCA1 and BRCA2 carriers with a prior diagnosis of ovarian cancer, 392 carriers with a diagnosis of breast cancer and 249 carriers with neither cancer. Fifty-eight women had both forms of cancer. Five hundred and ninety-five women had a BRCA1 mutation and 183 women had a BRCA2 mutation. Overall, there was no association between disease status and the presence of the PROGINS allele. Information on oral contraception use was available for 663 of the 778 carriers of BRCA1 or BRCA2 mutations. Among the 449 subjects with a history of oral contraceptive use (74 cases and 365 controls), no modifying effect of PROGINS was observed [odds ratio (OR) 0.8; 95% confidence interval (CI) 0.5-1.3]. Among the 214 carriers with no past exposure to oral contraceptives, the presence of one or more PROGINS alleles was associated with an OR of 2.4 for ovarian cancer, compared to women without ovarian cancer and with no PROGINS allele (P=0.004; 95% CI 1.4-4.3). The association was present after adjustment for ethnic group and for year of birth.

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