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

Abstract

Background 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. Methods A population- based case-control study in three counties of the Philadelphia Metropolitan area was undertaken. We evaluated eight PGR candidate SNPs and eighteen 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). Results 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 three-fold (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. Conclusion 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.

Hormone-related pathways and risk of breast cancer subtypes in African American women

“…Multiple studies have reported breast cancer associations with PGR SNP rs1042838 [68–71], but a later, larger meta-analysis showed no association [72]. Breast cancer associations have also been reported in a small AA sample for rs590688 and rs10895054 [73]. These three SNPs were not associated with breast cancer in the present study.…”

Does circulating progesterone mediate the associations of single nucleotide polymorphisms in progesterone receptor (PGR)-related genes with mammographic breast density in premenopausal women?

“…Rs11224565 is a noncoding variant located in the 3'UTR and could potentially influence BMI via alterations in gene expression [40,46]. Prior work has shown that rs10895054 is associated with increased risk of breast cancer in African American women [47]. BMI at age 10 is inversely associated with breast cancer risk in premenopausal women [48].…”

Racial disparities of differentiated thyroid carcinoma: clinical behavior, treatments, and long-term outcomes

“…Differences in tumor biology and genetic variances might explain the racial disparities in our study. Black Americans with breast cancer were reported to have differences in progesterone receptor genes [ 26 ]. Such differences could also exist in thyroid cancer between white and black Americans.…”