有丝分裂调控途径多态性与胰腺癌风险和预后的关联。
Association of mitotic regulation pathway polymorphisms with pancreatic cancer risk and outcome.
机构信息
Department of Laboratory Medicine and Pathology, Stabile 2-42, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA.
出版信息
Cancer Epidemiol Biomarkers Prev. 2010 Jan;19(1):251-7. doi: 10.1158/1055-9965.EPI-09-0629.
BACKGROUND
Mitosis is a highly regulated process that serves to ensure the fidelity of cell division. The disruption of mitotic regulators leading to aneuploidy and polyploidy is commonly observed in cancer cells. Single nucleotide polymorphisms (SNP) in regulators of mitosis may promote chromosome missegregation and influence pancreatic cancer and/or survival.
METHODS
Thirty-four SNPs, previously associated with breast cancer risk, from 33 genes involved in the regulation of mitosis, were investigated for associations with pancreatic cancer risk in 1,143 Caucasian patients with pancreatic adenocarcinoma and 1,097 unaffected controls from the Mayo Clinic. Associations with survival from pancreatic cancer were also assessed using 1,030 pancreatic cancer cases with known outcome.
RESULTS
Two SNPs in the APC (rs2431238) and NIN (rs10145182) loci, of 34 examined, were significantly associated with pancreatic cancer risk (P = 0.035 and P = 0.038, respectively). Further analyses of individuals categorized by smoking and body mass index identified several SNPs displaying significant associations (P < 0.05) with pancreatic cancer risk, including APC rs2431238 in individuals with high body mass index (>/=30; P = 0.031) and NIN rs10145182 in ever smokers (P = 0.01). In addition, survival analyses detected significant associations between SNPs in EIF3S10 and overall survival (P = 0.009), SNPs from five genes and survival in resected cancer cases (P < 0.05), and SNPs from two other genes (P < 0.05) and survival of locally advanced cancer cases.
CONCLUSION
Common variation in genes encoding regulators of mitosis may independently influence pancreatic cancer susceptibility and survival.
背景
有丝分裂是一个高度调控的过程，其目的是确保细胞分裂的保真度。在癌细胞中，有丝分裂调节因子的破坏导致非整倍体和多倍体是常见的。有丝分裂调节因子的单核苷酸多态性（SNP）可能会促进染色体错误分离，并影响胰腺癌和/或生存。
方法
在来自参与有丝分裂调节的 33 个基因的 34 个先前与乳腺癌风险相关的 SNP 中，调查了它们与 1143 名患有胰腺腺癌的白种人患者和来自梅奥诊所的 1097 名未受影响的对照者的胰腺癌风险之间的关联。使用已知结局的 1030 例胰腺癌病例评估与胰腺癌生存的关联。
结果
在 34 个检查的 SNP 中，APC（rs2431238）和 NIN（rs10145182）基因座中的两个 SNP 与胰腺癌风险显著相关（分别为 P = 0.035 和 P = 0.038）。对按吸烟和体重指数分类的个体进行进一步分析，确定了几个与胰腺癌风险显著相关的 SNP（P < 0.05），包括在高体重指数（>/=30；P = 0.031）个体中 APC rs2431238 和曾吸烟者的 NIN rs10145182（P = 0.01）。此外，生存分析检测到 EIF3S10 中的 SNP 与总生存之间存在显著关联（P = 0.009）、来自五个基因的 SNP 与切除癌病例的生存之间存在显著关联（P < 0.05）、以及来自两个其他基因的 SNP（P < 0.05）与局部晚期癌病例的生存之间存在显著关联。
结论
有丝分裂调节因子编码基因的常见变异可能独立地影响胰腺癌的易感性和生存。
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