Background: Younger age at diagnosis and poorer prognosis in African American women (AAW) with breast cancer have led to a number of studies evaluating gene expression differences in tumors from AAW compared to those from Caucasian women (CW). Studies have found that PSPHL expression is significantly higher not only in breast but also in prostate and endometrial tumors from African Americans compared to Caucasians. SNP rs6700 in the 3’ UTR of PSPHL has been found to correlate with expression. Here, we investigated how rs6700 affects PSPHL expression levels in AAW and CW with and without breast cancer.

Methods: Genomic DNA was isolated from 74 women with (35 AAW and 39 CW) and 37 women without breast cancer (23 AAW and 14 CW). rs6700

was genotyped using TaqMan SNP Genotyping assay C__314922_10.

PSPHL expression levels in breast tissue were measured in these same women using TaqMan Gene Expression assay Hs00863464_m1 using RNA isolated from laser microdissected breast tumor cells or normal breast tissue from women with or without breast cancer, respectively.

Results:PSPHL expression in breast tumors from AAW was significantly higher than in CW (P = 6 x 10-6). The median fold change in expression in AAW was 42.2; while only 2 (6%) AAW had no detectable expression of PSPHL, 21/39 (54%) CW did not express PSPHL. The minor allele frequency (T) in AAW with breast cancer was 0.41 compared to 0.06 in CW with breast cancer. In both AAW and CW, median levels of PSPHL expression were lowest (15.45 in AAW, 0 in CW) in women with the C/Cgenotype. In addition, all patients whose tumors had no detectable PSPHL expression had the C/C genotype. In women without breast cancer, the C/C genotype was also correlated with lower PSPHL expression and was more frequent among CW compared to AAW (79% and 39%, respectively).

Conclusions:PSPHL is more highly expressed in both diseased and normal breast tissue from AAW compared to CW and expression of PSPHL correlated with rs6700 genotypes. Although the function of PSPHL is unknown, it may function in cellular proliferation. Higher expression in AAW may, therefore, promote the development of tumors in AAW. It must be noted, however, that the frequency of the C allele is significantly lower in the African American population as a whole (53% vs. 92%); therefore, differences described here may reflect population differences rather than any specific contribution to breast cancer etiology. However, due to the higher expression of PSPHL in African Americans with other hormone-dependent cancers, its role in tumorigenesis requires further study.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-13-04.