评估前列腺癌早期检测项目中高危男性的早发性前列腺癌遗传标志物的临床作用。
Assessing the clinical role of genetic markers of early-onset prostate cancer among high-risk men enrolled in prostate cancer early detection.
机构信息
Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
出版信息
Cancer Epidemiol Biomarkers Prev. 2012 Jan;21(1):53-60. doi: 10.1158/1055-9965.EPI-11-0727. Epub 2011 Dec 5.
BACKGROUND
Men with familial prostate cancer and African American men are at risk for developing prostate cancer at younger ages. Genetic markers predicting early-onset prostate cancer may provide clinically useful information to guide screening strategies for high-risk men. We evaluated clinical information from six polymorphisms associated with early-onset prostate cancer in a longitudinal cohort of high-risk men enrolled in prostate cancer early detection with significant African American participation.
METHODS
Eligibility criteria include ages 35 to 69 with a family history of prostate cancer or African American race. Participants undergo screening and biopsy per study criteria. Six markers associated with early-onset prostate cancer [rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)] were genotyped. Cox models were used to evaluate time to prostate cancer diagnosis and prostate-specific antigen (PSA) prediction for prostate cancer by genotype. Harrell's concordance index was used to evaluate predictive accuracy for prostate cancer by PSA and genetic markers.
RESULTS
Four hundred and sixty participants with complete data and ≥ 1 follow-up visit were included. Fifty-six percent were African American. Among African American men, rs6983561 genotype was significantly associated with earlier time to prostate cancer diagnosis (P = 0.005) and influenced prediction for prostate cancer by the PSA (P < 0.001). When combined with PSA, rs6983561 improved predictive accuracy for prostate cancer compared with PSA alone among African American men (PSA = 0.57 vs. PSA + rs6983561 = 0.75, P = 0.03).
CONCLUSIONS
Early-onset marker rs6983561 adds potentially useful clinical information for African American men undergoing prostate cancer risk assessment. Further study is warranted to validate these findings.
IMPACT
Genetic markers of early-onset prostate cancer have potential to refine and personalize prostate cancer early detection for high-risk men.
背景
有家族前列腺癌病史的男性和非裔美国男性罹患前列腺癌的风险更高，且发病年龄更早。预测早发性前列腺癌的遗传标志物可能为高危男性提供具有临床应用价值的信息，从而指导他们的筛查策略。我们评估了六个与早发性前列腺癌相关的遗传多态性在一个有大量非裔美国人参与的高危男性前列腺癌早期检测的纵向队列中的临床信息。
方法
入选标准包括年龄 35 岁至 69 岁，有前列腺癌家族史或非裔美国人。根据研究标准，参与者接受筛查和活检。与早发性前列腺癌相关的六个标记物 [rs2171492（7q32），rs6983561（8q24），rs10993994（10q11），rs4430796（17q12），rs1799950（17q21）和 rs266849（19q13）]进行基因分型。使用 Cox 模型评估按基因型评估前列腺癌诊断和前列腺特异性抗原（PSA）的时间。Harrell 的一致性指数用于评估 PSA 和遗传标记物对前列腺癌的预测准确性。
结果
共纳入 460 名数据完整且≥1 次随访的参与者，其中 56%为非裔美国人。在非裔美国男性中，rs6983561 基因型与前列腺癌诊断时间更早显著相关（P=0.005），并影响了 PSA 对前列腺癌的预测（P<0.001）。与 PSA 相比，rs6983561 与 PSA 联合应用时，可提高非裔美国男性前列腺癌的预测准确性（PSA=0.57 vs. PSA+rs6983561=0.75，P=0.03）。
结论
早发性标志物 rs6983561 为接受前列腺癌风险评估的非裔美国男性提供了潜在有用的临床信息。需要进一步的研究来验证这些发现。
影响
早发性前列腺癌的遗传标志物有可能为高危男性的前列腺癌早期检测提供更精确和个性化的信息。
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