Association of CASP8 D302H polymorphism with reduced risk of aggressive prostate carcinoma.
Association of CASP8 D302H polymorphism with reduced risk of aggressive prostate carcinoma.
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DOI：
10.1002/pros.21098
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发表时间：
2010-05-01
期刊：
影响因子：
2.8
通讯作者：
Kibel, Adam S.
中科院分区：
文献类型：
--
作者：
Lubahn, Jessica;Berndt, Sonja I.;Jin, Carol H.;Klim, Aleksandra;Luly, Jason;Wu, William S.;Isaacs, Sarah;Wiley, Kathleen;Isaacs, William B.;Suarez, Brian K.;Hayes, Richard B.;Kibel, Adam S.
由于侵袭性前列腺癌和惰性前列腺癌（PCa）的临床病程显著不同，区分这些表型的标志物至关重要。细胞凋亡是细胞生长和转移的重要保护机制。因此，该途径的功能障碍是癌症进展的关键步骤。因此，凋亡基因的遗传变异是侵袭性PCa的潜在标志物。最近在乳腺癌中的研究表明，CASP 8 D302 H（rs 1045485）的组氨酸变体是一种保护性风险等位基因。我们在796例侵袭性病例和2,060例对照的汇总分析中检验了Hvariant对侵袭性PCa具有保护作用的假设。结果H等位基因与侵袭性PCa风险降低相关（OR/等位基因= 0.67，95%CI：0.54-0.83，Ptrend = 0.0003）。欧洲裔美国人（ORper等位基因= 0.68; 95%CI：0.54-0.86）和非洲裔美国人（ORper等位基因= 0.61; 95%CI：0.34-1.10）的结果相似。我们进一步从前列腺、肺、结直肠、卵巢（PLCO）人群的1,160例病例和1,166例对照的全系列中确定，H等位基因的保护作用往往限于高级别和晚期PCa。（所有病例OR/等位基因= 0.94; 95% CI：0.79-1.11;局部低度疾病OR/等位基因= 0.98; 95% CI：0.79-1.23;侵袭性疾病OR/等位基因= 0.73; 95% CI：0.50-1.07）。这些结果表明，CASP 8 D302 H的组氨酸变体是侵袭性PCa的保护性等位基因，具有潜在的实用性，可用于鉴定具有这种临床显著表型的不同风险的患者。
Because of the dramatically different clinical course of aggressive and indolent prostate carcinoma (PCa), markers that distinguish between these phenotypes are of critical importance. Apoptosis is an important protective mechanism for unrestrained cellular growth and metastasis. Therefore, dysfunction in this pathway is a key step in cancer progression. As such, genetic variants in apoptosis genes are potential markers of aggressive PCa. Recent work in breast carcinoma has implicated the histidine variant of CASP8 D302H (rs1045485) as a protective risk allele. We tested the hypothesis that the Hvariant was protective for aggressive PCa in a pooled analysis of 796 aggressive cases and 2,060 controls. RESULTS. The H allele was associated with a reduced risk of aggressive PCa (ORper allele = 0.67, 95% CI: 0.54–0.83, Ptrend = 0.0003). The results were similar for European-Americans (ORper allele = 0.68; 95% CI: 0.54–0.86) and African-Americans (ORper allele = 0.61; 95% CI: 0.34–1.10). We further determined from the full series of 1,160 cases and 1,166 controls in the Prostate, Lung, Colorectal, Ovarian (PLCO) population that the protective effect of the H allele tended to be limited to high-grade and advanced PCa (all cases ORper allele = 0.94; 95% CI: 0.79–1.11; localized, low-grade disease ORper allele = 0.98; 95% CI: 0.79–1.23; and aggressive disease ORper allele = 0.73; 95% CI: 0.50–1.07). These results suggest that histidine variant of CASP8 D302H is a protective allele for aggressive PCa with potential utility for identification of patients at differential risk for this clinically significant phenotype.
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