Zabaleta Jovanny, Lin Hui-Yi, Sierra Rosa A, Hall M Craig, Clark Peter E, Sartor Oliver A, Hu Jennifer J, Ochoa Augusto C
Department of Genetics, Louisiana State University Health Sciences Center, 533 Bolivar Street, CSRB 455, New Orleans, LA 70112, USA.
Carcinogenesis. 2008 Mar;29(3):573-8. doi: 10.1093/carcin/bgm277. Epub 2008 Jan 3.
Prostate cancer (CaP) is the second leading cause of cancer death in American men. Chronic inflammation has been one of several factors associated with the development of CaP. Single-nucleotide polymorphisms (SNPs) in cytokine genes have been associated with increased inflammation, increased cytokine production and possibly increased CaP risk. However, the effects of cytokine SNPs on CaP susceptibility have not been consistent. Using the genomic DNA collected in a CaP case-control study (557 cases and 547 controls), we pilot tested the interactions of nine functionally characterized SNPs of three cytokine genes in CaP risk using the multivariate adaptive regression splines (MARS)-logit models. African-Americans with the IL10-819TT genotype had a lower CaP risk [odds ratio (OR) = 0.27, 95% confidence interval (CI) = 0.07-1.01], but subjects with the genotype combination of IL1B-511CT/TT and IL10-592CC had a higher CaP risk (OR = 2.56, 95% CI = 1.09-6.02). In Caucasians, higher CaP risk was associated with the IL10-1082AG/GG genotype (OR = 3.62, 95% CI = 1.42-9.28), the genotype combination of IL10-1082AA plus IL1B-31TT/TC (OR = 2.92, 95% CI = 1.13-7.55) and the genotype combination of TNF-238GG plus IL10-592AA (OR = 2.14, 95% CI = 1.05-4.38). Our results highlight the importance of cytokine SNPs and their interactions in CaP risk.
前列腺癌（CaP）是美国男性癌症死亡的第二大主要原因。慢性炎症一直是与CaP发生相关的几个因素之一。细胞因子基因中的单核苷酸多态性（SNP）与炎症增加、细胞因子产生增加以及可能增加的CaP风险相关。然而，细胞因子SNP对CaP易感性的影响并不一致。利用在一项CaP病例对照研究（557例病例和547例对照）中收集的基因组DNA，我们使用多变量自适应回归样条（MARS）-logit模型对三个细胞因子基因的九个功能特征SNP在CaP风险中的相互作用进行了初步测试。具有IL10 - 819TT基因型的非裔美国人患CaP的风险较低[比值比（OR）= 0.27，95%置信区间（CI）= 0.07 - 1.01]，但具有IL1B - 511CT/TT和IL10 - 592CC基因型组合的受试者患CaP的风险较高（OR = 2.56，95% CI = 1.09 - 6.02）。在白种人中，较高的CaP风险与IL10 - 1082AG/GG基因型（OR = 3.62，95% CI = 1.42 - 9.28）、IL10 - 1082AA加IL1B - 31TT/TC的基因型组合（OR = 2.92，95% CI = 1.13 - 7.55）以及TNF - 238GG加IL10 - 592AA的基因型组合（OR = 2.14，95% CI = 1.05 - 4.38）相关。我们的结果突出了细胞因子SNP及其相互作用在CaP风险中的重要性。
