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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., ((c) 2006 Wiley-Liss, Inc.)

Purpose: Body size has been hypothesized to affect the risk of prostate cancer (PCa). However, previous studies have provided conflicting results, in that some show positive associations, whereas others indicate inverse associations or null findings. To further understand this we examined the effects of weight, height, body mass index and lean body mass (LBM) on PCa risk and aggressiveness in a sibling based case-control study., Materials and Methods: A total of 439 cases were recruited at major medical institutions in Cleveland, Ohio and Detroit, Michigan, and 479 unaffected brothers were recruited as controls. Conditional logistic regression with robust variance estimation was used to evaluate the association between body size and PCa., Results: Higher LBM was inversely associated with PCa, especially in men with more aggressive disease or a later age at onset. Comparing those above and below the 25th percentile showed an OR of 0.49 (95% CI 0.28 to 0.84) and 0.28 (95% CI 0.14, 0.56), respectively. Similar inverse patterns were observed for weight. No noteworthy associations were observed between PCa and height or body mass index., Conclusions: These observations suggest that PCa may be affected by LBM.