期刊
ONCOLOGIST
卷 16, 期 1, 页码 61-70出版社
ALPHAMED PRESS
DOI: 10.1634/theoncologist.2010-0127
关键词
DNA mismatch repair; Pancreatic cancer; Single-nucleotide polymorphism; Survival
类别
资金
- National Institutes of Health (NIH) [CA098380]
- SPORE [CA101936]
- NIH Cancer Center [CA16672]
- Lockton Research Funds
- NATIONAL CANCER INSTITUTE [P20CA101936, R01CA098380, P30CA016672] Funding Source: NIH RePORTER
Purpose. DNA mismatch repair (MMR) maintains genomic stability and mediates cellular response to DNA damage. We aim to demonstrate whether MMR genetic variants affect overall survival (OS) in pancreatic cancer. Materials and Methods. Using the Sequenom method in genomic DNA, we retrospectively genotyped 102 single-nucleotide polymorphisms (SNPs) of 13 MMR genes from 706 patients with pancreatic adenocarcinoma seen at The University of Texas MD Anderson Cancer Center. Association between genotype and OS was evaluated using multivariable Cox proportional hazard regression models. Results. At a false discovery rate of 1% (p <=. 0015), 15 SNPs of EXO1, MLH1, MSH2, MSH3, MSH6, PMS2, PMS2L3, TP73, and TREX1 in patients with localized disease (n = 333) and 6 SNPs of MSH3, MSH6, and TP73 in patients with locally advanced or metastatic disease (n = 373) were significantly associated with OS. In multivariable Cox proportional hazard regression models, SNPs of EXO1, MSH2, MSH3, PMS2L3, and TP73 in patients with localized disease, MSH2, MSH3, MSH6, and TP73 in patients with locally advanced or metastatic disease, and EXO1, MGMT, MSH2, MSH3, MSH6, PMS2L3, and TP73 in all patients remained significant predictors for OS (p <=. 0015) after adjusting for all clinical predictors and all SNPs with p <= .0015 in single-locus analysis. Sixteen haplotypes of EXO1, MLH1, MSH2, MSH3, MSH6, PMS2, PMS2L3, RECQL, TP73, and TREX1 significantly correlated with OS in all patients (p <= .001). Conclusion. MMR gene variants may have potential value as prognostic markers for OS in pancreatic cancer patients. The Oncologist 2011; 16: 61-70
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据