Michaud Dominique S, Daugherty Sarah E, Berndt Sonja I, Platz Elizabeth A, Yeager Meredith, Crawford E David, Hsing Ann, Huang Wen-Yi, Hayes Richard B
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
Cancer Res. 2006 Apr 15;66(8):4525-30. doi: 10.1158/0008-5472.CAN-05-3987.
Chronic intraprostatic inflammation is suspected to play a role in the pathogenesis of prostate cancer. Polymorphisms in cytokine genes can influence inflammation and immune response and may be related to the risk of prostate cancer. Four common single nucleotide polymorphisms (SNPs) in the genes encoding interleukin-1B (IL-1B), IL-6, and IL-8 were assessed in 503 prostate cancer cases and 652 controls, and three SNPs in IL-10 were assessed in an additional 817 prostate cancer cases and 1,190 controls (for a total of 1,320 prostate cancer cases and 1,255 controls). Cases and controls were selected from the on-going Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial and were frequency matched on age, ethnicity, time-period since initial screening, and date of blood draw. Single-locus analyses were conducted using conditional logistic regression. In addition, we did a haplotype analysis for the three IL-10 SNPs tested. Overall, no associations were detected between the seven polymorphisms in the four cytokine genes examined in this study and prostate cancer risk. Further stratifying by use of nonsteroidal anti-inflammatory drugs did not modify the associations. Findings were similar for early or advanced prostate cancers. Similarly, we observed no association between the major IL-10 haplotypes and the risk of prostate cancer. At least seven common polymorphisms in genes of inflammatory cytokines IL-1B, IL-6, IL-8, and IL-10 do not seem to play a role in the risk of prostate cancer.
慢性前列腺内炎症被怀疑在前列腺癌的发病机制中起作用。细胞因子基因多态性可影响炎症和免疫反应,可能与前列腺癌风险相关。在503例前列腺癌病例和652例对照中评估了编码白细胞介素-1B(IL-1B)、IL-6和IL-8的基因中的四种常见单核苷酸多态性(SNP),并在另外817例前列腺癌病例和1190例对照中评估了IL-10中的三种SNP(总共1320例前列腺癌病例和1255例对照)。病例和对照选自正在进行的前列腺、肺、结肠直肠和卵巢癌筛查试验,并在年龄、种族、初次筛查后的时间段和采血日期上进行频率匹配。使用条件逻辑回归进行单基因座分析。此外,我们对所检测的三种IL-10 SNP进行了单倍型分析。总体而言,在本研究中检测的四种细胞因子基因中的七种多态性与前列腺癌风险之间未发现关联。使用非甾体抗炎药进一步分层并未改变这种关联。早期或晚期前列腺癌的结果相似。同样,我们观察到主要的IL-10单倍型与前列腺癌风险之间无关联。炎症细胞因子IL-1B、IL-6、IL-8和IL-10基因中至少七种常见多态性似乎在前列腺癌风险中不起作用。