Progesterone receptor variation and risk of ovarian cancer is limited to the invasive endometrioid subtype: Results from the ovarian cancer association consortium pooled analysis

C. L. Pearce, A. H. Wu, S. A. Gayther, A. E. Bale, P. A. Beck, J. Beesley, S. Chanock, D. W. Cramer, R. DiCioccio, R. Edwards, Z. S. Fredericksen, M. Garcia-Closas, E. L. Goode, A. C. Green, L. C. Hartmann, E. Hogdall, S. K. Kjær, J. Lissowska, V. McGuire, F. ModugnoK. Moysich, R. B. Ness, S. J. Ramus, H. A. Risch, T. A. Sellers, H. Song, D. O. Stram, K. L. Terry, P. M. Webb, D. C. Whiteman, A. S. Whittemore, W. Zheng, P. D P Pharoah, G. Chenevix-Trench, M. C. Pike, J. Schildkraut, A. Berchuck

Research output: Contribution to journalArticle

Abstract

There is evidence that progesterone plays a role in the aetiology of invasive epithelial ovarian cancer. Therefore, genes involved in pathways that regulate progesterone may be candidates for susceptibility to this disease. Previous studies have suggested that genetic variants in the progesterone receptor gene (PGR) may be associated with ovarian cancer risk, although results have been inconsistent. We have established an international consortium to pool resources and data from many ovarian cancer case-control studies in an effort to identify variants that influence risk. In this study, three PGR single nucleotide polymorphisms (SNPs), for which previous data have suggested they affect ovarian cancer risk, were examined. These were +331 C/T (rs10895068), PROGINS (rs1042838), and a 3′ variant (rs608995). A total of 4788 ovarian cancer cases and 7614 controls from 12 case-control studies were included in this analysis. Unconditional logistic regression was used to model the association between each SNP and ovarian cancer risk and two-sided P-values are reported. Overall, risk of ovarian cancer was not associated with any of the three variants studied. However, in histopathological subtype analyses, we found a statistically significant association between risk of endometrioid ovarian cancer and the PROGINS allele (n=651, OR=1.17, 95% CI=1.01-1.36, P=0.036). We also observed borderline evidence of an association between risk of endometrioid ovarian cancer and the +331C/T variant (n=725 cases; OR=0.80, 95% CI 0.62-1.04, P=0.100). These data suggest that while these three variants in the PGR are not associated with ovarian cancer overall, the PROGINS variant may play a modest role in risk of endometrioid ovarian cancer.

Original languageEnglish (US)
Pages (from-to)282-288
Number of pages7
JournalBritish Journal of Cancer
Volume98
Issue number2
DOIs
StatePublished - Jan 29 2008
Externally publishedYes

Fingerprint

Progesterone Receptors
Ovarian Neoplasms
Genes
Single Nucleotide Polymorphism
Progesterone
Case-Control Studies
Disease Susceptibility
Logistic Models
Alleles

Keywords

  • Endometrioid ovarian cancer
  • Ovarian cancer
  • Pooled analyses
  • Progesterone receptor
  • PROGINS
  • SNPs

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Progesterone receptor variation and risk of ovarian cancer is limited to the invasive endometrioid subtype : Results from the ovarian cancer association consortium pooled analysis. / Pearce, C. L.; Wu, A. H.; Gayther, S. A.; Bale, A. E.; Beck, P. A.; Beesley, J.; Chanock, S.; Cramer, D. W.; DiCioccio, R.; Edwards, R.; Fredericksen, Z. S.; Garcia-Closas, M.; Goode, E. L.; Green, A. C.; Hartmann, L. C.; Hogdall, E.; Kjær, S. K.; Lissowska, J.; McGuire, V.; Modugno, F.; Moysich, K.; Ness, R. B.; Ramus, S. J.; Risch, H. A.; Sellers, T. A.; Song, H.; Stram, D. O.; Terry, K. L.; Webb, P. M.; Whiteman, D. C.; Whittemore, A. S.; Zheng, W.; Pharoah, P. D P; Chenevix-Trench, G.; Pike, M. C.; Schildkraut, J.; Berchuck, A.

In: British Journal of Cancer, Vol. 98, No. 2, 29.01.2008, p. 282-288.

Research output: Contribution to journalArticle

Pearce, CL, Wu, AH, Gayther, SA, Bale, AE, Beck, PA, Beesley, J, Chanock, S, Cramer, DW, DiCioccio, R, Edwards, R, Fredericksen, ZS, Garcia-Closas, M, Goode, EL, Green, AC, Hartmann, LC, Hogdall, E, Kjær, SK, Lissowska, J, McGuire, V, Modugno, F, Moysich, K, Ness, RB, Ramus, SJ, Risch, HA, Sellers, TA, Song, H, Stram, DO, Terry, KL, Webb, PM, Whiteman, DC, Whittemore, AS, Zheng, W, Pharoah, PDP, Chenevix-Trench, G, Pike, MC, Schildkraut, J & Berchuck, A 2008, 'Progesterone receptor variation and risk of ovarian cancer is limited to the invasive endometrioid subtype: Results from the ovarian cancer association consortium pooled analysis', British Journal of Cancer, vol. 98, no. 2, pp. 282-288. https://doi.org/10.1038/sj.bjc.6604170
Pearce, C. L. ; Wu, A. H. ; Gayther, S. A. ; Bale, A. E. ; Beck, P. A. ; Beesley, J. ; Chanock, S. ; Cramer, D. W. ; DiCioccio, R. ; Edwards, R. ; Fredericksen, Z. S. ; Garcia-Closas, M. ; Goode, E. L. ; Green, A. C. ; Hartmann, L. C. ; Hogdall, E. ; Kjær, S. K. ; Lissowska, J. ; McGuire, V. ; Modugno, F. ; Moysich, K. ; Ness, R. B. ; Ramus, S. J. ; Risch, H. A. ; Sellers, T. A. ; Song, H. ; Stram, D. O. ; Terry, K. L. ; Webb, P. M. ; Whiteman, D. C. ; Whittemore, A. S. ; Zheng, W. ; Pharoah, P. D P ; Chenevix-Trench, G. ; Pike, M. C. ; Schildkraut, J. ; Berchuck, A. / Progesterone receptor variation and risk of ovarian cancer is limited to the invasive endometrioid subtype : Results from the ovarian cancer association consortium pooled analysis. In: British Journal of Cancer. 2008 ; Vol. 98, No. 2. pp. 282-288.
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abstract = "There is evidence that progesterone plays a role in the aetiology of invasive epithelial ovarian cancer. Therefore, genes involved in pathways that regulate progesterone may be candidates for susceptibility to this disease. Previous studies have suggested that genetic variants in the progesterone receptor gene (PGR) may be associated with ovarian cancer risk, although results have been inconsistent. We have established an international consortium to pool resources and data from many ovarian cancer case-control studies in an effort to identify variants that influence risk. In this study, three PGR single nucleotide polymorphisms (SNPs), for which previous data have suggested they affect ovarian cancer risk, were examined. These were +331 C/T (rs10895068), PROGINS (rs1042838), and a 3′ variant (rs608995). A total of 4788 ovarian cancer cases and 7614 controls from 12 case-control studies were included in this analysis. Unconditional logistic regression was used to model the association between each SNP and ovarian cancer risk and two-sided P-values are reported. Overall, risk of ovarian cancer was not associated with any of the three variants studied. However, in histopathological subtype analyses, we found a statistically significant association between risk of endometrioid ovarian cancer and the PROGINS allele (n=651, OR=1.17, 95{\%} CI=1.01-1.36, P=0.036). We also observed borderline evidence of an association between risk of endometrioid ovarian cancer and the +331C/T variant (n=725 cases; OR=0.80, 95{\%} CI 0.62-1.04, P=0.100). These data suggest that while these three variants in the PGR are not associated with ovarian cancer overall, the PROGINS variant may play a modest role in risk of endometrioid ovarian cancer.",
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T1 - Progesterone receptor variation and risk of ovarian cancer is limited to the invasive endometrioid subtype

T2 - Results from the ovarian cancer association consortium pooled analysis

AU - Pearce, C. L.

AU - Wu, A. H.

AU - Gayther, S. A.

AU - Bale, A. E.

AU - Beck, P. A.

AU - Beesley, J.

AU - Chanock, S.

AU - Cramer, D. W.

AU - DiCioccio, R.

AU - Edwards, R.

AU - Fredericksen, Z. S.

AU - Garcia-Closas, M.

AU - Goode, E. L.

AU - Green, A. C.

AU - Hartmann, L. C.

AU - Hogdall, E.

AU - Kjær, S. K.

AU - Lissowska, J.

AU - McGuire, V.

AU - Modugno, F.

AU - Moysich, K.

AU - Ness, R. B.

AU - Ramus, S. J.

AU - Risch, H. A.

AU - Sellers, T. A.

AU - Song, H.

AU - Stram, D. O.

AU - Terry, K. L.

AU - Webb, P. M.

AU - Whiteman, D. C.

AU - Whittemore, A. S.

AU - Zheng, W.

AU - Pharoah, P. D P

AU - Chenevix-Trench, G.

AU - Pike, M. C.

AU - Schildkraut, J.

AU - Berchuck, A.

PY - 2008/1/29

Y1 - 2008/1/29

N2 - There is evidence that progesterone plays a role in the aetiology of invasive epithelial ovarian cancer. Therefore, genes involved in pathways that regulate progesterone may be candidates for susceptibility to this disease. Previous studies have suggested that genetic variants in the progesterone receptor gene (PGR) may be associated with ovarian cancer risk, although results have been inconsistent. We have established an international consortium to pool resources and data from many ovarian cancer case-control studies in an effort to identify variants that influence risk. In this study, three PGR single nucleotide polymorphisms (SNPs), for which previous data have suggested they affect ovarian cancer risk, were examined. These were +331 C/T (rs10895068), PROGINS (rs1042838), and a 3′ variant (rs608995). A total of 4788 ovarian cancer cases and 7614 controls from 12 case-control studies were included in this analysis. Unconditional logistic regression was used to model the association between each SNP and ovarian cancer risk and two-sided P-values are reported. Overall, risk of ovarian cancer was not associated with any of the three variants studied. However, in histopathological subtype analyses, we found a statistically significant association between risk of endometrioid ovarian cancer and the PROGINS allele (n=651, OR=1.17, 95% CI=1.01-1.36, P=0.036). We also observed borderline evidence of an association between risk of endometrioid ovarian cancer and the +331C/T variant (n=725 cases; OR=0.80, 95% CI 0.62-1.04, P=0.100). These data suggest that while these three variants in the PGR are not associated with ovarian cancer overall, the PROGINS variant may play a modest role in risk of endometrioid ovarian cancer.

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KW - Endometrioid ovarian cancer

KW - Ovarian cancer

KW - Pooled analyses

KW - Progesterone receptor

KW - PROGINS

KW - SNPs

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