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Plasminogen activator inhibitor type-1 (PAI-1) polymorphism 4G/5G is associated with prostate cancer among men with a positive family history.
Prostate. 2007 Feb 01; 67(2):172-7.P

Abstract

BACKGROUND

Variation in the expression of plasminogen activator inhibitor type-1 (PAI-1) is associated with many human diseases, including several types of cancer. In particular, tumor cell overexpression of PAI-1 has been found to inhibit prostate cancer tumor growth, angiogenesis, and metastasis in mouse models. Normal host cell expression of PAI-1 is influenced by the 4G/5G insertion/deletion polymorphism in the promoter region of the PAI-1 gene. To evaluate the effect of PAI-1 expression on cancer development, we examined the association of the 4G/5G polymorphism in a sibling-based case-control study of prostate cancer.

METHODS

One thousand one hundred thirty seven subjects, 655 cases, and 482 sibling controls from 526 families, were recruited from the major medical institutions in the greater Cleveland, OH area and from the Henry Ford Health System, Detroit, MI. A Cox age-of-onset model with robust variance estimation was used to evaluate the association between the PAI-1 4G/5G polymorphism and prostate cancer.

RESULTS

No association was observed between the PAI-1 4G/5G polymorphism and prostate cancer in the entire sample. We did, however, identify a statistically significant association between the PAI-1 4G/5G polymorphism and prostate cancer in subjects with a family history of this disease (OR = 1.28, 95% CI 1.02-1.61, P-value = 0.036). The PAI-1 5G/5G genotype, associated with lower PAI-1 expression, appears to drive this result as it was associated with an increased risk of prostate cancer and an earlier mean age of onset compared to those with the 4G/4G genotype (OR = 1.83, 95% CI 1.12-2.99) while the 4G/5G genotype group did not show a significant difference in prostate cancer risk compared to the 4G/4G genotype group (OR = 0.98, 95% CI 0.75-1.28).

CONCLUSIONS

These observations suggest that the 4G/5G polymorphism in PAI-1 may explain some of the increased risk and earlier mean age of onset of prostate cancer due to a positive family history.

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Authors+Show Affiliations

Jorgenson E
Department of Epidemiology and Biostatistics, Center for Human Genetics, University of California, San Francisco, San Francisco, California 94143-0794, USA. Eric.Jorgenson@ucsf.edu
Deitcher SR
No affiliation info available
Cicek M
No affiliation info available
Liu X
No affiliation info available
Plummer S
No affiliation info available
Casey G
No affiliation info available
Witte JS
No affiliation info available

MeSH

Age of OnsetFamily HealthGenetic Predisposition to DiseaseGenotypeHumansMaleMichiganMiddle AgedOhioPlasminogen Activator Inhibitor 1Polymorphism, GeneticProstatic NeoplasmsRisk FactorsSiblingsSurveys and Questionnaires

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17044080

Citation

Jorgenson, Eric, et al. "Plasminogen Activator Inhibitor Type-1 (PAI-1) Polymorphism 4G/5G Is Associated With Prostate Cancer Among Men With a Positive Family History." The Prostate, vol. 67, no. 2, 2007, pp. 172-7.
Jorgenson E, Deitcher SR, Cicek M, et al. Plasminogen activator inhibitor type-1 (PAI-1) polymorphism 4G/5G is associated with prostate cancer among men with a positive family history. Prostate. 2007;67(2):172-7.
Jorgenson, E., Deitcher, S. R., Cicek, M., Liu, X., Plummer, S., Casey, G., & Witte, J. S. (2007). Plasminogen activator inhibitor type-1 (PAI-1) polymorphism 4G/5G is associated with prostate cancer among men with a positive family history. The Prostate, 67(2), 172-7.
Jorgenson E, et al. Plasminogen Activator Inhibitor Type-1 (PAI-1) Polymorphism 4G/5G Is Associated With Prostate Cancer Among Men With a Positive Family History. Prostate. 2007 Feb 1;67(2):172-7. PubMed PMID: 17044080.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Plasminogen activator inhibitor type-1 (PAI-1) polymorphism 4G/5G is associated with prostate cancer among men with a positive family history. AU - Jorgenson,Eric, AU - Deitcher,Steven R, AU - Cicek,Mine, AU - Liu,Xin, AU - Plummer,Sarah, AU - Casey,Graham, AU - Witte,John S, PY - 2006/10/18/pubmed PY - 2007/2/21/medline PY - 2006/10/18/entrez SP - 172 EP - 7 JF - The Prostate JO - Prostate VL - 67 IS - 2 N2 - BACKGROUND: Variation in the expression of plasminogen activator inhibitor type-1 (PAI-1) is associated with many human diseases, including several types of cancer. In particular, tumor cell overexpression of PAI-1 has been found to inhibit prostate cancer tumor growth, angiogenesis, and metastasis in mouse models. Normal host cell expression of PAI-1 is influenced by the 4G/5G insertion/deletion polymorphism in the promoter region of the PAI-1 gene. To evaluate the effect of PAI-1 expression on cancer development, we examined the association of the 4G/5G polymorphism in a sibling-based case-control study of prostate cancer. METHODS: One thousand one hundred thirty seven subjects, 655 cases, and 482 sibling controls from 526 families, were recruited from the major medical institutions in the greater Cleveland, OH area and from the Henry Ford Health System, Detroit, MI. A Cox age-of-onset model with robust variance estimation was used to evaluate the association between the PAI-1 4G/5G polymorphism and prostate cancer. RESULTS: No association was observed between the PAI-1 4G/5G polymorphism and prostate cancer in the entire sample. We did, however, identify a statistically significant association between the PAI-1 4G/5G polymorphism and prostate cancer in subjects with a family history of this disease (OR = 1.28, 95% CI 1.02-1.61, P-value = 0.036). The PAI-1 5G/5G genotype, associated with lower PAI-1 expression, appears to drive this result as it was associated with an increased risk of prostate cancer and an earlier mean age of onset compared to those with the 4G/4G genotype (OR = 1.83, 95% CI 1.12-2.99) while the 4G/5G genotype group did not show a significant difference in prostate cancer risk compared to the 4G/4G genotype group (OR = 0.98, 95% CI 0.75-1.28). CONCLUSIONS: These observations suggest that the 4G/5G polymorphism in PAI-1 may explain some of the increased risk and earlier mean age of onset of prostate cancer due to a positive family history. SN - 0270-4137 UR - https://www.unboundmedicine.com/medline/citation/17044080/Plasminogen_activator_inhibitor_type_1__PAI_1__polymorphism_4G/5G_is_associated_with_prostate_cancer_among_men_with_a_positive_family_history_ L2 - https://doi.org/10.1002/pros.20512 DB - PRIME DP - Unbound Medicine ER -