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Progesterone receptor polymorphisms and risk of breast cancer: results from two Australian breast cancer studies

  • Epidemiology
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Abstract

Association studies aimed at identifying breast cancer susceptibility variants in the progesterone receptor (PGR) gene have been previously reported in the literature with conflicting results, ranging from a protective effect conferred by the PROGINS allele in German Caucasian women, to an increased risk for the leucine variant of the Val660Leu (rs1042838) polymorphism in East Anglian cases. We report the results of genotype and haplotype analyses of five PGR polymorphisms, +44C/T (rs518162), +331G/A (rs10895068), V660L (rs1042838), H770H (rs1042839) and Q886Q (rs500760), conducted on 1,847 Australian breast cancer cases (including 276 cases from a cohort of multiple-case breast cancer families) and 833 controls. Genotype and haplotype analyses of the five polymorphisms showed no evidence of an association with breast cancer (p > 0.3). We also conducted a meta-analysis of the V660 L (rs1042838) polymorphism on our and six other published studies including 10,205 cases and 11,320 controls. Compared to the VV homozygotes, VL heterozygotes and LL homozygotes were associated with a non-significant increased risk for breast cancer [Odds ratio (OR)VL, 1.06; 95% confidence intervals (95% CI), 0.97–1.15, ORLL, 1.05; 95% CI, 0.75–1.49]. Analysis of a per-leucine allele risk under a codominant model, however, suggested a significant leucine-allele dose effect, ORper-L, 1.07; 95% CI, 1.02–1.13, p = 0.01. We conclude that the leucine allele of the V660L SNP may be associated with a small increase in breast cancer risk, while the other four PGR SNPs, +44C/T (rs518162), +331G/A (rs10895068), H770H (rs1042839) and Q886Q (rs500760), do not substantially increase breast cancer risk.

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Acknowledgments

We wish to thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (funded by NHMRC grants 145684 and 288704) for their contributions to this resource, and the many families who contribute to kConFab. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. We thank the Margaret McCredie, Graham Giles and Melissa Southey for their role in the establishment of the Australian Breast Cancer Family Study. GCT is supported by a NHMRC Senior Principal Research Fellowship, and ABS by a NHMRC Career Development Award.

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Authors and Affiliations

  1. Cancer and Cell Biology, Queensland Institute of Medical Research, c/o Royal Brisbane Hospital Post Office, Herston, Brisbane, QLD, 4029, Australia

    Sharon E. Johnatty, Amanda B. Spurdle, Jonathan Beesley, Xiaoqing Chen, David L. Duffy & Georgia Chenevix-Trench

  2. Centre for Genetic Epidemiology, The University of Melbourne, Carlton, Melbourne, VIC, Australia

    John L. Hopper

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  1. Sharon E. Johnatty
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  2. Amanda B. Spurdle
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  3. Jonathan Beesley
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  4. Xiaoqing Chen
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  5. John L. Hopper
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  6. David L. Duffy
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  7. Georgia Chenevix-Trench
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The Kathleen Cuningham Consortium for Research in Familial Breast Cancer

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Correspondence to Georgia Chenevix-Trench.

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Johnatty, S.E., Spurdle, A.B., Beesley, J. et al. Progesterone receptor polymorphisms and risk of breast cancer: results from two Australian breast cancer studies. Breast Cancer Res Treat 109, 91–99 (2008). https://doi.org/10.1007/s10549-007-9627-3

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