Genetic Sequence Variants are Associated with Severity of Lower Urinary Tract Symptoms and Prostate Cancer Susceptibility
Genetic Sequence Variants are Associated with Severity of Lower Urinary Tract Symptoms and Prostate Cancer Susceptibility
复制标题
DOI：
10.1016/j.juro.2012.11.044
复制
发表时间：
2013-03-01
影响因子：
6.6
通讯作者：
Catalona, William J.
中科院分区：
文献类型：
--
作者：
Helfand, Brian T.;Hu, Qiaoyan;Catalona, William J.
目的：虽然明确的遗传因素是下尿路症状和良性前列腺增生症的基础，但很少有研究确定特定的遗传因素。相比之下，最近的全基因组关联研究发现单核苷酸多态会增加前列腺癌的风险。其中一些单核苷酸多态也可能是良性前列腺增生症手术治疗的易感因素。我们确定这些单核苷酸多态是否也与下尿路症状严重程度和良性前列腺增生症药物使用有关。材料和方法：对1168名健康白人男性志愿者进行了38个单核苷酸多态与前列腺癌风险相关的基因分型。前瞻性记录美国泌尿学会症状指数评分和良性前列腺增生症的药物治疗情况。结果：包括染色体5p15上的rs2736098在内的多个单核苷酸多态与良性前列腺增生症的用药有关。在调整了其他遗传变异、患者年龄和用药后，9q33.2上的rs1571801(OR 1.31，95%CI 1.0~1.74)和Xp11上的rs5945572(OR 1.28，95%CI 1.04~1.59)与泌尿症状增加显著相关。8q24上的rs445114与患者的下尿路症状相关(OR 0.83，95%CI 0.66~1.01)。结论：在38个易患前列腺癌的单核苷酸多态中，有3个与下尿路症状表型相关。这些单核苷酸多态可能有助于改善男性下尿路症状/良性前列腺增生症的特征。
Purpose: While a clear heritable component underlies lower urinary tract symptoms and benign prostatic hyperplasia, few studies have identified specific genetic factors. In contrast, recent genome-wide association studies identified single nucleotide polymorphisms that increase prostate cancer risk. Some of these single nucleotide polymorphisms may also predispose to surgical intervention for benign prostatic hyperplasia. We determined whether these single nucleotide polymorphisms are also associated with lower urinary tract symptom severity and benign prostatic hyperplasia medication use.Materials and Methods: The genotypes of 38 single nucleotide polymorphisms previously associated with prostate cancer risk were determined for 1,168 healthy white male volunteers. American Urological Association symptom index score and medication for benign prostatic hyperplasia were documented prospectively. Statistical analyses were done to compare the frequency of the single nucleotide polymorphisms with American Urological Association symptom index and benign prostatic hyperplasia medication use.Results: Several single nucleotide polymorphisms, including rs2736098 on chromosome 5p15, showed a significant relationship with benign prostatic hyperplasia medication. After adjusting for the other genetic variants, patient age and medication use, rs1571801 on chromosome 9q33.2 (OR 1.31, 95% CI 1.0-1.74) and rs5945572 on chromosome Xp11 (OR 1.28, 95% CI 1.04-1.59) were significantly associated with increased urinary symptoms. In contrast, rs445114 on chromosome 8q24 was marginally associated with decreased urinary symptoms (OR 0.83, 95% CI 0.66-1.01).Conclusions: Of 38 single nucleotide polymorphisms that predispose to prostate cancer we identified 3 that are also associated with a well characterized lower urinary tract symptom phenotype. These single nucleotide polymorphisms may aid in the improved characterization of men with lower urinary tract symptoms/benign prostatic hyperplasia.