Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
BJU Int. 2014 May;113(5b):E150-6. doi: 10.1111/bju.12264. Epub 2013 Aug 13.
To validate six previously identified markers among men at increased risk of prostate cancer (African-American men and those with a family history of prostate cancer) enrolled in the Prostate Cancer Risk Assessment Program (PRAP), a prostate cancer screening study.
Eligibility criteria for PRAP include age 35-69 years with a family history of prostate cancer, African-American ethnicity regardless of family history, and known BRCA gene mutations. The genome-wide association study markers assessed included rs2736098 (5p15.33), rs10993994 (10q11), rs10788160 (10q26), rs11067228 (12q24), rs4430796 (17q12) and rs17632542 (19q13.33). Genotyping methods included either the Taqman(®) single nucleotide polymorphism (SNP) genotyping assay (Applied Biosystems, Foster City, CA, USA) or pyrosequencing. Linear regression models were used to evaluate the association between individual markers and log-transformed baseline PSA levels, while adjusting for potential confounders.
A total of 707 participants (37% Caucasian, 63% African-American) with clinical and genotype data were included in the analysis. Rs10788160 (10q26) was strongly associated with PSA levels among Caucasian participants in the high-risk group (P < 0.01), with a 33.2% increase in PSA level with each A-allele carried. Furthermore, rs10993994 (10q11) was found to be associated with PSA level (P = 0.03) in Caucasian men in the high-risk group, with a 15% increase in PSA level with each T-allele carried. A PSA adjustment model based on allele carrier status at rs10788160 and rs10993994 was proposed, specific to high-risk Caucasian men.
Genetic variation at 10q may be particularly important in personalizing the interpretation of PSA level for Caucasian men in the high-risk group. Such information may have clinical relevance in shared decision-making and individualized prostate cancer screening strategies for Caucasian men in the high-risk group, although further study is warranted.
验证前列腺癌风险评估计划（PRAP）中高危前列腺癌男性（非裔美国男性和有前列腺癌家族史的男性）中先前确定的六个标志物。
PRAP 的入选标准包括年龄 35-69 岁，有前列腺癌家族史，非裔美国人，无论家族史如何，以及已知的 BRCA 基因突变。评估的全基因组关联研究标志物包括 rs2736098（5p15.33）、rs10993994（10q11）、rs10788160（10q26）、rs11067228（12q24）、rs4430796（17q12）和 rs17632542（19q13.33）。基因分型方法包括 Taqman（®）单核苷酸多态性（SNP）基因分型检测（Applied Biosystems，Foster City，CA，USA）或焦磷酸测序。线性回归模型用于评估个体标记与基线 PSA 水平的对数变换之间的关联，同时调整潜在的混杂因素。
共纳入 707 名（37%白种人，63%非裔美国人）具有临床和基因型数据的参与者进行分析。在高危组的白种人参与者中，rs10788160（10q26）与 PSA 水平呈强关联（P<0.01），每携带一个 A-等位基因，PSA 水平增加 33.2%。此外，rs10993994（10q11）与高危组白种人男性的 PSA 水平相关（P=0.03），每携带一个 T-等位基因，PSA 水平增加 15%。提出了一种基于 rs10788160 和 rs10993994 等位基因携带状态的 PSA 调整模型，专门针对高危白种人男性。
10q 上的遗传变异可能在为高危白种人男性解释 PSA 水平方面具有特别重要的意义。这种信息可能对高危白种人男性的共同决策和个体化前列腺癌筛查策略具有临床意义，尽管需要进一步研究。
