A high fat intake has been associated with prostate cancer risk, and gene polymorphisms of lipoprotein lipase (LPL) play an important role in plasma lipoprotein metabolism. We herein analyzed the association of LPL gene polymorphisms with the risk of prostate cancer in a Japanese population. Three single nucleotide polymorphisms (SNPs) of LPL designated as Ser447stop, HindIII and PvuII were genotyped by the polymerase chain reaction-restriction fragment length polymorphism method in 273 prostate cancer patients, 205 benign prostatic hyperplasia (BPH) patients and 230 male controls. The men with the CG + GG genotypes of the Ser447stop polymorphism had an increased risk of prostate cancer compared to those with the CC genotype [age-adjusted odds ratio (aOR) = 1.625; 95% CI = 1.068-2.471; p = 0.023]. Furthermore, the increased risk associated with the CG + GG genotypes was more strongly observed in patients with high-grade cancers (aOR = 2.843; 95% CI = 1.252-6.458; p = 0.039) or metastatic diseases (aOR = 2.300; 95% CI = 1.042-5.074; p = 0.013), whereas the risk was not significant in those with low- to intermediate-grade cancers or nonmetastatic diseases. In the HindIII and PvuII polymorphisms, there was no significant difference between the prostate cancer patients and the controls, and no significant results as for tumor grade and stage. None of the 3 polymorphisms showed any association with the risk of BPH. Our results suggest that the LPL Ser447stop polymorphism is a common genetic modifier for the development of prostate cancer, particularly that of high-grade and/or high-stage, in a Japanese population.
(c) 2004 Wiley-Liss, Inc.