Bladder cancer SNP panel predicts susceptibility and survival.

Bladder cancer SNP panel predicts susceptibility and survival.
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DOI:
10.1007/s00439-009-0645-6
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发表时间:
2009-06
期刊:
影响因子:
5.3
通讯作者:
Karagas MR
Karagas MR
中科院分区:
生物学2区
文献类型:
--
作者:
Andrew AS;Gui J;Sanderson AC;Mason RA;Morlock EV;Schned AR;Kelsey KT;Marsit CJ;Moore JH;Karagas MR

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在西方国家,膀胱癌是男性第四大常见恶性肿瘤,女性第八大常见癌症。调节端粒维持、有丝分裂、炎症和凋亡的基因中的单核苷酸多态(SNPs)尚未被广泛评估为该病的病因。通过对832例膀胱癌患者和1191名对照的人群研究,我们评估了基因变异与癌症易感性或存活率的关系。研究结果包括与野生型相比,甲基代谢基因MTHFD2变异(OR 1.7 95%CI 1.3-2.3)、端粒酶TEP1变异(OR 1.8 95%CI 1.2-2.6)以及炎症反应基因变异IL8RB(OR 0.6 95%CI 0.5-0.9)的风险增加。生存期缩短与CASP9等凋亡基因变异有关(HR 1.8,95%CI 1.1-3.0)。解毒基因EPHX1的变异体存活时间更长(HR 0.4(95%CI 0.2-0.8))。这些基因现在可以在多个研究人群中进行评估,以识别和验证适合临床使用的SNPs。
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.
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