Xu Jianfeng, Meyers Deborah A, Sterling David A, Zheng Siqun L, Catalona William J, Cramer Scott D, Bleecker Eugene R, Ohar Jill
Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Cancer Epidemiol Biomarkers Prev. 2002 Jul;11(7):664-9.
Testing for serum prostate-specific antigen (PSA) levels has been widely used to screen for prostate cancer. However, PSA testing has low specificity and sensitivity because PSA is not prostate cancer-specific. PSA is encoded by the APS gene, and the expression of this gene is regulated by androgens. W. Xue et al. Cancer Res., 60: 839-841, 2000 reported recently that serum PSA levels are associated with a G/A polymorphism at androgen responsive element 1 (ARE1) of APS and/or the CAG repeats in exon 1 of the androgen receptor (AR) gene. This result, if confirmed, may significantly increase the specificity and sensitivity of PSA testing by incorporating genotype-specific thresholds. In this study, we tested for the association between serum PSA levels and these single nucleotide polymorphisms (SNPs) in a large sample of 518 men. For the AR gene, we observed slightly (but not statistically significant) higher mean serum PSA levels in men with shorter CAG repeats (<or=21) or shorter GGC repeats (<or=16). For the ARE1 of the APS, we found slightly (but not statistically significant) lower PSA levels in men with the AA genotype. It is worth noting that this observation is opposite to the findings of W. Xue et al. Cancer Res., 60: 839-841, 2000. We hypothesize that the effects of ARE1 and AR genotypes on mean PSA levels may reflect the effect of other causal polymorphisms in these genes, which are in linkage disequilibrium with these polymorphisms. A systematic approach is required to identify sequence variants in these genes and other related genes, and to test for an association between these variants and PSA levels in large samples.
检测血清前列腺特异性抗原（PSA）水平已被广泛用于前列腺癌筛查。然而，PSA检测的特异性和敏感性较低，因为PSA并非前列腺癌所特有。PSA由APS基因编码，该基因的表达受雄激素调控。W. Xue等人于2000年发表在《癌症研究》（Cancer Res.）第60卷第839 - 841页的研究报告称，血清PSA水平与APS基因雄激素反应元件1（ARE1）处的G/A多态性和/或雄激素受体（AR）基因外显子1中的CAG重复序列有关。如果这一结果得到证实，通过纳入基因型特异性阈值，可能会显著提高PSA检测的特异性和敏感性。在本研究中，我们在518名男性的大样本中检测了血清PSA水平与这些单核苷酸多态性（SNP）之间的关联。对于AR基因，我们观察到CAG重复序列较短（≤21）或GGC重复序列较短（≤16）的男性，其平均血清PSA水平略高（但无统计学意义）。对于APS基因的ARE1，我们发现AA基因型的男性PSA水平略低（但无统计学意义）。值得注意的是，这一观察结果与W. Xue等人于2000年发表在《癌症研究》第60卷第839 - 841页的研究结果相反。我们推测，ARE1和AR基因型对平均PSA水平的影响可能反映了这些基因中其他因果多态性的作用，这些因果多态性与这些多态性处于连锁不平衡状态。需要一种系统的方法来识别这些基因和其他相关基因中的序列变异，并在大样本中检测这些变异与PSA水平之间的关联。
