Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20852, USA.
Prostate. 2012 Jan;72(1):65-71. doi: 10.1002/pros.21407. Epub 2011 Apr 25.
Androgens and inflammation have been implicated in the etiology of several cancers, including prostate cancer. Serum androgens have been shown to correlate with markers of inflammation and expression of inflammation-related genes.
In this report, we evaluated associations between 9,932 single nucleotide polymorphisms (SNPs) marking common genetic variants in 774 inflammation-related genes and four serum androgen levels (total testosterone [T], bioavailable T [BioT]; 5α-androstane-3α, 17β-diol glucuronide [3αdiol G], and 4-androstene-3,17-dione [androstenedione]), in 560 healthy men (median age 64 years) drawn from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Baseline serum androgens were measured by radioimmunoassay. Genotypes were determined as part of the Cancer Genetic Markers of Susceptibility Study genome-wide scan. SNP-hormone associations were evaluated using linear regression of hormones adjusted for age. Gene-based P values were generated using an adaptive rank truncated product (ARTP) method.
Suggestive associations were observed for two inflammation-related genes and circulating androgen levels (false discovery rate [FDR] q-value <0.1) in both SNP and gene-based tests. Specifically, T was associated with common variants in MMP2 and CD14, with the most significant SNPs being rs893226G > T in MMP2 and rs3822356T > C in CD14 (FDR q-value = 0.09 for both SNPs). Other genes implicated in either SNP or gene-based tests were IK with T and BioT, PRG2 with T, and TNFSF9 with androstenedione.
These results suggest possible cross-talk between androgen levels and inflammation pathways, but larger studies are needed to confirm these findings and to further clarify the interrelationship between inflammation and androgens and their effects on cancer risk.
雄激素和炎症与几种癌症的病因有关，包括前列腺癌。已经表明，血清雄激素与炎症标志物和炎症相关基因的表达相关。
在本报告中，我们评估了 774 个炎症相关基因中标记常见遗传变异的 9932 个单核苷酸多态性（SNP）与四种血清雄激素水平（总睾酮[T]、生物可利用 T[BioT]；5α-雄烷-3α,17β-二醇葡糖苷酸[3αdiol G]和 4-雄烯-3,17-二酮[雄烯二酮]）之间的关联，这些 SNP 标记了来自前列腺、肺、结直肠和卵巢癌症筛查试验的 560 名健康男性（中位年龄 64 岁）。使用放射免疫测定法测量基线血清雄激素。作为癌症遗传易感性标记物研究全基因组扫描的一部分确定基因型。使用经过年龄调整的激素的线性回归评估 SNP-激素关联。使用自适应秩截断乘积（ARTP）方法生成基于基因的 P 值。
在 SNP 和基于基因的测试中，均观察到两个与炎症相关的基因和循环雄激素水平之间存在提示性关联（错误发现率[FDR]q 值<0.1）。具体而言，T 与 MMP2 和 CD14 中的常见变异体相关，最显著的 SNP 是 MMP2 中的 rs893226G>T 和 CD14 中的 rs3822356T>C（两个 SNP 的 FDR q 值均为 0.09）。在 SNP 或基于基因的测试中涉及的其他基因是 IK 与 T 和 BioT、PRG2 与 T 和 TNFSF9 与雄烯二酮。
这些结果表明，雄激素水平和炎症途径之间可能存在交叉对话，但需要更大的研究来证实这些发现，并进一步阐明炎症与雄激素之间的相互关系及其对癌症风险的影响。
