Andrew Angeline S, Gui Jiang, Sanderson Arthur C, Mason Rebecca A, Morlock Elaine V, Schned Alan R, Kelsey Karl T, Marsit Carmen J, Moore Jason H, Karagas Margaret R
Section of Biostatistics and Epidemiology, Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, NH 03756, USA.
Hum Genet. 2009 Jun;125(5-6):527-39. doi: 10.1007/s00439-009-0645-6. Epub 2009 Mar 1.
Bladder cancer is the fourth most common malignancy in men and the eighth most common in women in western countries. Single nucleotide polymorphisms (SNPs) in genes that regulate telomere maintenance, mitosis, inflammation, and apoptosis have not been assessed extensively for this disease. Using a population-based study with 832 bladder cancer cases and 1,191 controls, we assessed genetic variation in relation to cancer susceptibility or survival. Findings included an increased risk associated with variants in the methyl-metabolism gene, MTHFD2 (OR 1.7 95% CI 1.3-2.3), the telomerase TEP1 (OR 1.8 95% CI 1.2-2.6) and decreased risk associated with the inflammatory response gene variant IL8RB (OR 0.6 95% CI 0.5-0.9) compared to wild-type. Shorter survival was associated with apoptotic gene variants, including CASP9 (HR 1.8 95% CI 1.1-3.0). Variants in the detoxification gene EPHX1 experienced longer survival (HR 0.4 (95% CI 0.2-0.8). These genes can now be assessed in multiple study populations to identify and validate SNPs appropriate for clinical use.
在西方国家，膀胱癌是男性中第四大常见恶性肿瘤，女性中第八大常见恶性肿瘤。尚未对调节端粒维持、有丝分裂、炎症和细胞凋亡的基因中的单核苷酸多态性（SNP）进行广泛评估。我们采用一项基于人群的研究，纳入832例膀胱癌病例和1191例对照，评估了与癌症易感性或生存率相关的基因变异。研究结果包括，与野生型相比，甲基代谢基因MTHFD2的变异（比值比1.7，95%置信区间1.3 - 2.3）、端粒酶TEP1的变异（比值比1.8，95%置信区间1.2 - 2.6）与风险增加相关，而炎症反应基因变异IL8RB（比值比0.6，95%置信区间0.5 - 0.9）与风险降低相关。较短的生存期与凋亡基因变异相关，包括CASP9（风险比1.8，95%置信区间1.1 - 3.0）。解毒基因EPHX1的变异与较长的生存期相关（风险比0.4（95%置信区间0.2 - 0.8）。现在可以在多个研究人群中对这些基因进行评估，以识别和验证适用于临床的SNP。
