Clinical Breast Care Project, Henry M, Jackson Foundation for the Advancement of Military Medicine, 620 Seventh Street, Windber, PA 15963, USA.
BMC Genet. 2014 Mar 20;15:38. doi: 10.1186/1471-2156-15-38.
Phophoserine phosphatase-like (PSPHL) is expressed at significantly higher levels in breast tumors from African American women (AAW) compared to Caucasian women (CW). How overexpression of PSPHL contributes to outcome disparities is unclear, thus, molecular mechanisms driving expression differences between populations were evaluated.
PCR was used to detect deletion of 30-Kb of chromosome 7p11 including the first three exons of PSPHL using genomic DNA from AAW (199 with invasive breast cancer, 360 controls) and CW (invasive breast cancer =589, 364 controls). Gene expression levels were evaluated by qRT-PCR using RNA isolated from tumor tissue and blood. Data were analyzed using chi-square analysis and Mann-Whitney U-tests; P < 0.05 was used to define significance. Gene expression levels correlated with deletion status: patients homozygous for the deletion had no detectable expression of PSPHL, while heterozygous had expression levels 2.1-fold lower than those homozygous for retention of PSPHL. Homozygous deletion of PSPHL was detected in 61% of CW compared to 6% of AAW with invasive breast cancer (P < 0.0001); genotype frequencies did not differ significantly between AAW with and without breast cancer (P = 0.211).
Thus, deletion of 7p11, which prevents expression of PSPHL, is significantly higher in CW compared to AAW, suggesting that this 30-kb deletion and subsequent disruption of PSPHL may be a derived trait in Caucasians. The similar frequency of the deletion allele in AAW with and without invasive breast cancer suggests that this difference represent population stratification, and does not contribute to cancer disparities.
与高加索女性（CW）相比，非裔美国女性（AAW）的乳腺癌组织中磷酸丝氨酸磷酸酶样（PSPHL）的表达水平显著更高。PSPHL 的过表达如何导致结局差异尚不清楚，因此，评估了驱动人群之间表达差异的分子机制。
使用来自 AAW（199 例浸润性乳腺癌，360 例对照）和 CW（浸润性乳腺癌=589 例，364 例对照）的基因组 DNA，通过 PCR 检测 7p11 染色体 30-Kb 缺失，包括 PSPHL 的前三个外显子。使用肿瘤组织和血液分离的 RNA 通过 qRT-PCR 评估基因表达水平。使用卡方分析和曼-惠特尼 U 检验分析数据；P<0.05 用于定义显著性。基因表达水平与缺失状态相关：缺失纯合子患者中 PSPHL 无检测到表达，而杂合子的表达水平比 PSPHL 保留的纯合子低 2.1 倍。在 CW 中检测到 PSPHL 纯合缺失的比例为 61%，而在浸润性乳腺癌的 AAW 中为 6%（P<0.0001）；AAW 中有无乳腺癌的基因型频率无显著差异（P=0.211）。
因此，7p11 的缺失阻止了 PSPHL 的表达，在 CW 中明显高于 AAW，这表明这种 30-Kb 的缺失和随后的 PSPHL 破坏可能是白种人的衍生特征。在有无浸润性乳腺癌的 AAW 中缺失等位基因的相似频率表明这种差异代表了人群分层，而不会导致癌症差异。
