Background: Prostate cancer (PCa) accounts for 22% of the new cases diagnosed in Hispanic/Latino (H/L) men in the US. PCa has the highest incidence (38.3%) and mortality (16.4%) among all types of cancer diagnosed in Puerto Rico. We previously showed that PCa patients (n= 41) have a significant reduction of 59% in their levels of DNA repair capacity (DRC) when compared to controls (n= 14). This study aimed to evaluate DRC levels through the nucleotide excision repair (NER) pathway for the first time in 16 Puerto Rican H/L men with metastatic castration-resistant PCa (mCRPCa) while establishing comparisons with controls and PCa patients with indolent and aggressive disease. Methods: Blood samples and clinicopathological data from PCa cases (n= 71) and controls (n= 25) were evaluated. PCa cases were stratified into mCRPCa (n= 16), aggressive (n= 31), and indolent (n= 24). DRC levels through NER were measured in lymphocytes with the CometChip assay. The stratification by Gleason score (GS) was GS6 (n= 7), GS7 (n= 23), GS ≥ 8 (n= 20), and mCRPCa patients (n= 16). Results: Significant statistical differences were found when comparing the DRC values of the controls with any other of the four PCa patient groups. mCRPCa patients had the lowest mean DRC level of all four patient groups studied. The mean DRC level of mCRPCa patients was 6.65%, and compared to the controls, this represented a statistically significant reduction of 62% (p< 0.0001). Further analysis was performed to evaluate the contributions of age, anthropometric measurements, and prostate-specific antigen (PSA) levels to the DRC. Kaplan–Meier curves of mCRPCa revealed that survival probability decreased by approximately 50% by 30 months. This pilot study uses a blood-based phenotypic assay to present the first report of mCRPCa in Puerto Rican men and at a global level of DRC levels of mCRPCa patients. Conclusions: This study evaluated DRC levels through the NER pathway for the first time in 16 Puerto Rican H/L men with mCRPCa. Significant differences in DRC values were found between the controls and the three PCa patient groups. Kaplan–Meier curves revealed that survival probability decreased by approximately 50% by 30 months, and only 20% of the cohort was alive at 50 months, confirming the lethality of mCRPCa in this H/L population. This pilot study represents the first report of metastatic PCa in Puerto Rican men at a global level of DRC levels of mCRPCa patients using a blood-based phenotypic assay.
背景:前列腺癌(PCa)占美国西班牙裔/拉丁裔(H/L)男性新诊断病例的22%。在波多黎各诊断的所有癌症类型中,PCa的发病率(38.3%)和死亡率(16.4%)最高。我们先前的研究表明,与对照组(n=14)相比,PCa患者(n=41)的DNA修复能力(DRC)水平显著降低了59%。本研究首次旨在通过核苷酸切除修复(NER)途径评估16名患有转移性去势抵抗性前列腺癌(mCRPCa)的波多黎各H/L男性的DRC水平,并与对照组以及惰性和侵袭性PCa患者进行比较。 方法:对PCa病例(n=71)和对照组(n=25)的血液样本和临床病理数据进行了评估。PCa病例被分为mCRPCa组(n=16)、侵袭性组(n=31)和惰性组(n=24)。使用CometChip检测法在淋巴细胞中测量通过NER途径的DRC水平。根据格里森评分(GS)进行分层:GS6(n=7)、GS7(n=23)、GS≥8(n=20)以及mCRPCa患者(n=16)。 结果:将对照组的DRC值与四个PCa患者组中的任何一组进行比较时,均发现了显著的统计学差异。在所研究的四个患者组中,mCRPCa患者的平均DRC水平最低。mCRPCa患者的平均DRC水平为6.65%,与对照组相比,这代表了统计学上显著的62%的降低(p<0.0001)。进一步分析了年龄、人体测量指标和前列腺特异性抗原(PSA)水平对DRC的影响。mCRPCa患者的Kaplan-Meier曲线显示,生存概率在30个月时下降了约50%。这项初步研究使用基于血液的表型检测,首次报告了波多黎各男性mCRPCa患者在全球层面的DRC水平。 结论:本研究首次通过NER途径评估了16名患有mCRPCa的波多黎各H/L男性的DRC水平。在对照组和三个PCa患者组之间发现了DRC值的显著差异。Kaplan-Meier曲线显示,生存概率在30个月时下降了约50%,并且只有20%的队列成员在50个月时存活,这证实了mCRPCa在该H/L人群中的致死性。这项初步研究使用基于血液的表型检测,首次在全球层面报告了波多黎各男性mCRPCa患者的DRC水平。