Dataset Information

Association of progesterone receptor gene (PGR) variants and breast cancer risk in African American women.

ABSTRACT: Prolonged exposure to combined hormone replacement therapy (estrogen plus progestin) increases a woman's risk of breast cancer, whereas estrogen-only 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 population-based 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 = 0.56, 95 % CI 0.39-0.82, p value 0.003, corrected p value 0.03). For rs10895054, each addition of the T allele increased the risk of breast cancer compared to the A allele nearly threefold (OR = 2.9, 95 % CI 1.47-6.02, p value 0.002, corrected p value 0.04). 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 non-White populations may reveal additional cancer associations of interest.

SUBMITTER: Gabriel CA

PROVIDER: S-EPMC3810299 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Association of progesterone receptor gene (PGR) variants and breast cancer risk in African American women.

Gabriel Courtney A CA Mitra Nandita N Demichele Angela A Rebbeck Timothy T

Breast cancer research and treatment 20130614 3

Prolonged exposure to combined hormone replacement therapy (estrogen plus progestin) increases a woman's risk of breast cancer, whereas estrogen-only 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 population-based case-control study in three counties of the Philadelphia Metropolitan area was undertaken. We e ...[more]

PMID: 23764995

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Project description:INTRODUCTION:African American (AA) women diagnosed with breast cancer are more likely to have aggressive subtypes. Investigating differentially expressed genes between patient populations may help explain racial health disparities. Resistin, one such gene, is linked to inflammation, obesity, and breast cancer risk. Previous studies indicated that resistin expression is higher in serum and tissue of AA breast cancer patients compared to Caucasian American (CA) patients. However, resistin expression levels have not been compared between AA and CA patients in a stage- and subtype-specific context. Breast cancer prognosis and treatments vary by subtype. This work investigates differential resistin gene expression in human breast cancer tissues of specific stages, receptor subtypes, and menopause statuses in AA and CA women. METHODS:Differential gene expression analysis was performed using human breast cancer gene expression data from The Cancer Genome Atlas. We performed inter-race resistin gene expression level comparisons looking at receptor status and stage-specific data between AA and CA samples. DESeq was run to test for differentially expressed resistin values. RESULTS:Resistin RNA was higher in AA women overall, with highest values in receptor negative subtypes. Estrogen-, progesterone-, and human epidermal growth factor receptor 2- negative groups showed statistically significant elevated resistin levels in Stage I and II AA women compared to CA women. In inter-racial comparisons, AA women had significantly higher levels of resistin regardless of menopause status. In whole population comparisons, resistin expression was higher among Stage I and III estrogen receptor negative cases. In comparisons of molecular subtypes, resistin levels were significant higher in triple negative than in luminal A breast cancer. CONCLUSION:Resistin gene expression levels were significantly higher in receptor negative subtypes, especially estrogen receptor negative cases in AA women. Resistin may serve as an early breast cancer biomarker and possible therapeutic target for AA breast cancer.

Dataset Information

Association of progesterone receptor gene (PGR) variants and breast cancer risk in African American women.

Publications

Association of progesterone receptor gene (PGR) variants and breast cancer risk in African American women.

Similar Datasets

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