Podocalyxin variants and risk of prostate cancer and tumor aggressiveness

Graham Casey, Phillippa J. Neville, Xin Liu, Sarah J. Plummer, Mine Cicek, Lisa M. Krumroy, Anthony P. Curran, Michelle R. McGreevy, William J. Catalona, Eric A. Klein, John S. Witte

Research output: Contribution to journalArticle

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Abstract

We previously reported linkage of a prostate cancer tumor aggressiveness locus to chromosome 7q32-q33, a region also associated with a high frequency of allelic imbalance in prostate tumors. The smallest region of allelic imbalance contains the podocalyxin-like (PODXL) gene, which we evaluate here as a candidate prostate cancer aggressiveness gene mapping to 7q32-q33. DNA from probands of linked families was examined for germ-line mutations in PODXL. A variable in-frame deletion, four missense variants and two nonsense variants were identified in linked men. Variants that affected amino acid sequence were further evaluated for association with risk of prostate cancer and tumor aggressiveness in a family-based case-control population (439 cases and 479 sibling controls). The presence of any single in-frame deletion was positively associated with prostate cancer [odds ratio (OR) = 2.14, 95% confidence interval (95%CI) = 1.09-4.20, P = 0.03] and the presence of two copies of any deletion further increased risk (OR = 2.58, 95%CI = 1.23-5.45, P = 0.01). This finding was strengthened when stratifying among men with more aggressive disease (high grade or stage): OR = 3.04 for one deletion (95%CI = 1.01-9.15) and OR = 4.42 for two deletions (95%CI%1.32-14.85, P = 0.02). A weak positive association was also observed between prostate cancer risk and PODXL variant 340A (in linkage disequilibrium with another variant, 587T) (OR = 1.48, 95%CI = 1.02-2.14, P = 0.04). These results implicate PODXL as a candidate prostate cancer tumor aggressiveness gene mapping to chromosome 7q32-q33.

Original languageEnglish (US)
Pages (from-to)735-741
Number of pages7
JournalHuman Molecular Genetics
Volume15
Issue number5
DOIs
StatePublished - Mar 1 2006
Externally publishedYes

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Odds Ratio
Confidence Intervals
Allelic Imbalance
Neoplasms
Chromosome Mapping
Prostatic Neoplasms
Chromosomes
Germ-Line Mutation
Neoplasm Genes
Linkage Disequilibrium
podocalyxin
Prostate Cancer, Hereditary, 7
Siblings
Prostate
Amino Acid Sequence
DNA
Population
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Casey, G., Neville, P. J., Liu, X., Plummer, S. J., Cicek, M., Krumroy, L. M., ... Witte, J. S. (2006). Podocalyxin variants and risk of prostate cancer and tumor aggressiveness. Human Molecular Genetics, 15(5), 735-741. https://doi.org/10.1093/hmg/ddi487

Podocalyxin variants and risk of prostate cancer and tumor aggressiveness. / Casey, Graham; Neville, Phillippa J.; Liu, Xin; Plummer, Sarah J.; Cicek, Mine; Krumroy, Lisa M.; Curran, Anthony P.; McGreevy, Michelle R.; Catalona, William J.; Klein, Eric A.; Witte, John S.

In: Human Molecular Genetics, Vol. 15, No. 5, 01.03.2006, p. 735-741.

Research output: Contribution to journalArticle

Casey, G, Neville, PJ, Liu, X, Plummer, SJ, Cicek, M, Krumroy, LM, Curran, AP, McGreevy, MR, Catalona, WJ, Klein, EA & Witte, JS 2006, 'Podocalyxin variants and risk of prostate cancer and tumor aggressiveness', Human Molecular Genetics, vol. 15, no. 5, pp. 735-741. https://doi.org/10.1093/hmg/ddi487
Casey, Graham ; Neville, Phillippa J. ; Liu, Xin ; Plummer, Sarah J. ; Cicek, Mine ; Krumroy, Lisa M. ; Curran, Anthony P. ; McGreevy, Michelle R. ; Catalona, William J. ; Klein, Eric A. ; Witte, John S. / Podocalyxin variants and risk of prostate cancer and tumor aggressiveness. In: Human Molecular Genetics. 2006 ; Vol. 15, No. 5. pp. 735-741.
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abstract = "We previously reported linkage of a prostate cancer tumor aggressiveness locus to chromosome 7q32-q33, a region also associated with a high frequency of allelic imbalance in prostate tumors. The smallest region of allelic imbalance contains the podocalyxin-like (PODXL) gene, which we evaluate here as a candidate prostate cancer aggressiveness gene mapping to 7q32-q33. DNA from probands of linked families was examined for germ-line mutations in PODXL. A variable in-frame deletion, four missense variants and two nonsense variants were identified in linked men. Variants that affected amino acid sequence were further evaluated for association with risk of prostate cancer and tumor aggressiveness in a family-based case-control population (439 cases and 479 sibling controls). The presence of any single in-frame deletion was positively associated with prostate cancer [odds ratio (OR) = 2.14, 95{\%} confidence interval (95{\%}CI) = 1.09-4.20, P = 0.03] and the presence of two copies of any deletion further increased risk (OR = 2.58, 95{\%}CI = 1.23-5.45, P = 0.01). This finding was strengthened when stratifying among men with more aggressive disease (high grade or stage): OR = 3.04 for one deletion (95{\%}CI = 1.01-9.15) and OR = 4.42 for two deletions (95{\%}CI{\%}1.32-14.85, P = 0.02). A weak positive association was also observed between prostate cancer risk and PODXL variant 340A (in linkage disequilibrium with another variant, 587T) (OR = 1.48, 95{\%}CI = 1.02-2.14, P = 0.04). These results implicate PODXL as a candidate prostate cancer tumor aggressiveness gene mapping to chromosome 7q32-q33.",
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