National Human Genome Center at Howard University, Washington, DC 20059, USA.
Prostate. 2010 Feb 15;70(3):262-9. doi: 10.1002/pros.21060.
African American men have the highest rates of prostate cancer worldwide, and immunogenetic studies suggest that people of African descent have increased susceptibility to diseases of inflammation. Since genetic susceptibility is an etiological factor in prostate cancer, we hypothesize that sequence variants in the promoter region of the CD14 gene that regulate inflammation may modify individual susceptibility to this disease.
The CD14 promoter was screened for single-nucleotide polymorphisms (SNPs) using dHPLC. One variant, -260 C>T (rs2569190), was genotyped via restriction digest in all study participants (264 cases and 188 controls). The association of disease status and the polymorphism was analyzed by unconditional logistic regression. Odds ratios with 95% confidence intervals were calculated, stratifying by ethnicity and adjusting for age. Two-sided P-values of < or =0.05 were considered as statistically significant.
Eleven variants (four novel) were identified in the promoter region of CD14. A marginal association between the C genotypes (C/C + C/T) and prostate cancer was found (P = 0.07). When stratified by age, among men > or =55 years of age, the C genotypes were significantly associated with prostate cancer (P < 0.05). When stratified by self-reported ethnicity, African American males who had the C genotypes were at a higher risk for prostate cancer (P < 0.05).
This is the first study to show an association between the C genotypes of the CD14 (-260) variant and prostate cancer which supports the hypothesis that genetic variation in the inflammatory process can contribute to prostate cancer susceptibility in African American men.
全世界范围内，非裔美国男性的前列腺癌发病率最高，免疫遗传学研究表明，非裔人群更容易罹患炎症相关疾病。由于遗传易感性是非前列腺癌的病因之一，我们假设 CD14 基因启动子区域中调节炎症的序列变异可能会改变个体对这种疾病的易感性。
使用 dHPLC 筛选 CD14 启动子的单核苷酸多态性（SNP）。在所有研究参与者（264 例病例和 188 例对照）中，通过限制性酶切对 -260 C>T（rs2569190）变体进行基因分型。通过无条件逻辑回归分析疾病状态与多态性的相关性。计算优势比及其 95%置信区间，并按种族分层，同时调整年龄因素。双侧 P 值≤0.05 被认为具有统计学意义。
在 CD14 启动子区域发现了 11 个变体（4 个是新变体）。C 基因型（C/C+C/T）与前列腺癌之间存在边缘相关性（P=0.07）。按年龄分层，在年龄≥55 岁的男性中，C 基因型与前列腺癌显著相关（P<0.05）。按自我报告的种族分层，携带 C 基因型的非裔美国男性患前列腺癌的风险更高（P<0.05）。
这是第一项表明 CD14（-260）变体的 C 基因型与前列腺癌之间存在关联的研究，支持了炎症过程中的遗传变异可能导致非裔美国男性易患前列腺癌的假设。
