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窖蛋白-1 和 -2 基因变异与治疗后血清窖蛋白-1 与前列腺癌风险和结局的关系。

Association of caveolin-1 and -2 genetic variants and post-treatment serum caveolin-1 with prostate cancer risk and outcomes.

机构信息

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.

出版信息

Prostate. 2010 Jun 15;70(9):1020-35. doi: 10.1002/pros.21137.

Abstract

BACKGROUND

Caveolin-1 (cav-1) is overexpressed by metastatic prostate cancer (PC) cells. Pre-operative serum cav-1 levels have been shown to be a prognostic marker for PC recurrence. This study evaluated the relationship between post-treatment serum cav-1 levels and single nucleotide polymorphisms (SNPs) in the cav-1 and -2 genes with risk of PC, aggressive PC, PC recurrence or death.

METHODS

Two case-control studies of PC among men in Washington State were combined for this analysis. Cases (n = 1,458) were diagnosed in 1993-1996 or 2002-2005 and identified via a SEER cancer registry. Age-matched controls (n = 1,351) were identified via random digit dialing. Logistic regression was used to assess the relationship between exposures (19 haplotype-tagging SNPs from all subjects and post-treatment serum cav-1 levels from a sample of 202 cases and 226 controls) and PC risk and aggressive PC. Cox proportional hazards regression was used to assess the relationship between exposures and PC recurrence and death.

RESULTS

Rs9920 in cav-1 was associated with an increased relative risk of overall PC (OR(CT + CC) = 1.37, 95% CI = 1.12, 1.68) and aggressive PC (OR(CT + CC) = 1.57, 95% CI = 1.20, 2.06), but not with PC recurrence or death. High post-treatment serum cav-1 levels were not associated with PC risk, aggressive PC, or PC-specific death, but approached a significant inverse association with PC recurrence (hazard ratio = 0.69, 95% CI = 0.47, 1.00).

CONCLUSIONS

We found modest evidence for an association with a variant in the cav-1 gene and risk of overall PC and aggressive PC, which merits further study. We found no evidence that higher post-treatment serum cav-1 is associated with risk of aggressive PC or adverse PC outcomes.

摘要

背景

小窝蛋白-1(cav-1)在转移性前列腺癌(PC)细胞中过表达。术前血清 cav-1 水平已被证明是 PC 复发的预后标志物。本研究评估了治疗后血清 cav-1 水平与 cav-1 和 -2 基因中的单核苷酸多态性(SNP)与 PC、侵袭性 PC、PC 复发或死亡风险之间的关系。

方法

对华盛顿州的两项 PC 病例对照研究进行了合并分析。病例(n=1458)于 1993-1996 年或 2002-2005 年诊断,并通过 SEER 癌症登记处确定。年龄匹配的对照(n=1351)通过随机数字拨号确定。使用逻辑回归评估暴露(来自所有受试者的 19 个单倍型标记 SNP 和来自 202 例病例和 226 例对照的样本中的治疗后血清 cav-1 水平)与 PC 风险和侵袭性 PC 之间的关系。使用 Cox 比例风险回归评估暴露与 PC 复发和死亡之间的关系。

结果

cav-1 中的 rs9920 与总体 PC(OR(CT + CC)=1.37,95%CI=1.12,1.68)和侵袭性 PC(OR(CT + CC)=1.57,95%CI=1.20,2.06)的相对风险增加相关,但与 PC 复发或死亡无关。治疗后血清 cav-1 水平升高与 PC 风险、侵袭性 PC 或 PC 特异性死亡无关,但与 PC 复发呈显著负相关(风险比=0.69,95%CI=0.47,1.00)。

结论

我们发现 cav-1 基因中的变异与总体 PC 和侵袭性 PC 风险之间存在适度关联的证据,值得进一步研究。我们没有发现治疗后血清 cav-1 水平升高与侵袭性 PC 风险或不良 PC 结局相关的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b59/2875326/be672b71c188/nihms179300f1.jpg

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