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PSPHL and breast cancer in African American women: causative gene or population stratification?
BACKGROUND: 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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994543/ https://www.ncbi.nlm.nih.gov/pubmed/24650299 http://dx.doi.org/10.1186/1471-2156-15-38 |
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author | Rummel, Seth Penatzer, Cayla E Shriver, Craig D Ellsworth, Rachel E |
author_facet | Rummel, Seth Penatzer, Cayla E Shriver, Craig D Ellsworth, Rachel E |
author_sort | Rummel, Seth |
collection | PubMed |
description | BACKGROUND: 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. RESULTS: 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). CONCLUSIONS: 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. |
format | Online Article Text |
id | pubmed-3994543 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-39945432014-04-23 PSPHL and breast cancer in African American women: causative gene or population stratification? Rummel, Seth Penatzer, Cayla E Shriver, Craig D Ellsworth, Rachel E BMC Genet Research Article BACKGROUND: 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. RESULTS: 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). CONCLUSIONS: 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. BioMed Central 2014-03-20 /pmc/articles/PMC3994543/ /pubmed/24650299 http://dx.doi.org/10.1186/1471-2156-15-38 Text en Copyright © 2014 Rummel et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. |
spellingShingle | Research Article Rummel, Seth Penatzer, Cayla E Shriver, Craig D Ellsworth, Rachel E PSPHL and breast cancer in African American women: causative gene or population stratification? |
title | PSPHL and breast cancer in African American women: causative gene or population stratification? |
title_full | PSPHL and breast cancer in African American women: causative gene or population stratification? |
title_fullStr | PSPHL and breast cancer in African American women: causative gene or population stratification? |
title_full_unstemmed | PSPHL and breast cancer in African American women: causative gene or population stratification? |
title_short | PSPHL and breast cancer in African American women: causative gene or population stratification? |
title_sort | psphl and breast cancer in african american women: causative gene or population stratification? |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994543/ https://www.ncbi.nlm.nih.gov/pubmed/24650299 http://dx.doi.org/10.1186/1471-2156-15-38 |
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