Carboxypeptidase 4 gene variants and early-onset intermediate-to-high risk prostate cancer.
Carboxypeptidase 4 gene variants and early-onset intermediate-to-high risk prostate cancer.
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DOI：
10.1186/1471-2407-9-69
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发表时间：
2009-02-26
期刊：
影响因子：
3.8
通讯作者：
Witte JS
中科院分区：
文献类型：
--
作者：
Ross PL;Cheng I;Liu X;Cicek MS;Carroll PR;Casey G;Witte JS
羧肽酶 4 (CPA4) 是一种锌依赖性金属羧肽酶，位于染色体 7q32 上，该区域与前列腺癌侵袭性相关。 CPA4 参与组蛋白高度乙酰化途径，并可能调节影响前列腺上皮细胞生长和调节的肽的功能。我们检查了 CPA4 遗传变异与中高风险前列腺癌之间的关联。我们研究了来自俄亥俄州克利夫兰的 1012 名男性（506 名病例和 506 名对照）。所有病例诊断时格里森评分≥7，临床分期≥T2c，或PSA≥10ng/mL。对六种 CPA4 单核苷酸多态性进行了基因分型，并评估了它们与前列腺癌的关系。我们还评估了 CPA4 变异是否影响较早年龄（< 66 岁）诊断的男性的疾病风险。 CPA4 中的非同义编码 SNP（rs2171492、Cys303Gly）与年轻患者（< 66 岁）患侵袭性前列腺癌的风险增加相关。具体而言，携带 TT 基因型的男性被诊断患有中高风险疾病的风险大约增加两倍（优势比 = 1.83，p = 0.04）。在总体人群（所有年龄段）中，没有一个 CPA4 SNP 表现出与前列腺癌有统计学上的显着关联。 CPA4 的编码变异可能会增加年轻患者患中高风险前列腺癌的风险。需要进一步的工作来确定这种变异的功能方面并了解其对前列腺癌的生物学影响。此类工作可能会转化为对高风险个体进行更精确的筛查，并指导临床医生和患者对基因确定为高风险的患者采取更早、更明确的治疗方式。
Carboxypeptidase 4 (CPA4) is a zinc-dependent metallocarboxypeptidase on chromosome 7q32 in a region linked to prostate cancer aggressiveness. CPA4 is involved in the histone hyperacetylation pathway and may modulate the function of peptides that affect the growth and regulation of prostate epithelial cells. We examined the association between genetic variation in CPA4 and intermediate-to-high risk prostate cancer. We studied 1012 men (506 cases and 506 controls) from Cleveland, Ohio. All cases had Gleason ≥ 7, clinical stage ≥ T2c, or PSA ≥ 10 ng/mL at diagnosis. Six CPA4 single-nucleotide polymorphisms were genotyped, and evaluated for their relation to prostate cancer. We also evaluated whether CPA4 variants influence risk of disease among men diagnosed at an earlier age (< 66 years). The nonsynonymous coding SNP (rs2171492, Cys303Gly) in CPA4 was associated with an increased risk of aggressive prostate cancer among younger patients (< 66 years). Specifically, men carrying the TT genotype had an approximately two-fold increased risk for being diagnosed with intermediate-to-high risk disease (Odds Ratio = 1.83, p = 0.04). In the overall population (all ages) none of the CPA4 SNPs demonstrated a statistically significant association with prostate cancer. Coding variation in CPA4 may confer increased risk of intermediate-to-high risk prostate cancer among younger patients. Further work is needed to identify the functional aspects of this variation and understand its biological effects on prostate cancer. Such work may translate into more precise screening of higher risk individuals as well as guiding clinicians and patients toward earlier and more definitive treatment modalities in patients genetically identified as higher risk.