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Title of Journal: Breast Cancer Res Treat

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Abbravation: Breast Cancer Research and Treatment

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Springer US

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DOI

10.1002/jcc.21445

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1573-7217

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Association of progesterone receptor gene Emphas

Authors: Courtney A Gabriel Nandita Mitra Angela DeMichele Timothy Rebbeck
Publish Date: 2013/06/14
Volume: 139, Issue: 3, Pages: 833-843
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Abstract

Prolonged exposure to combined hormone replacement therapy estrogen plus progestin increases a woman’s risk of breast cancer whereas estrogenonly hormone replacement therapy does not This suggests that progesterone may play a role in breast carcinogenesis Association studies have reported inconsistent relationships between progesterone receptor gene variants and breast cancer A populationbased case–control study in three counties of the Philadelphia Metropolitan area was undertaken We evaluated 8 PGR candidate SNPs and 18 PGR tagging SNPS in 487 breast cancer cases and 843 controls using multivariable logistic regression with adjustment for combined hormone replacement therapy use Separate analyses were conducted for European Americans EA 399 cases 490 controls and African Americans AA 88 cases 353 controls In EAs no significant associations were observed with the investigated PGR variants In AAs two tagging SNPs rs590688 and rs10895054 were statistically significantly associated with breast cancer For rs590688 each addition of the C allele was protective compared to the G allele OR = 056 95  CI 039–082 p value 0003 corrected p value 003 For rs10895054 each addition of the T allele increased the risk of breast cancer compared to the A allele nearly threefold OR = 29 95  CI 147–602 p value 0002 corrected p value 004 Three haplotype blocks all containing rs590688 were found to be significantly associated with breast cancer risk Environmental exposures namely parity and obesity modified the effect of both SNPs on breast cancer risk in EA This is the first study to find an association between two PGR variants and breast cancer in AA women These results suggest that studies of PGR variants in other nonWhite populations may reveal additional cancer associations of interest

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