Pancreatic Cancer Susceptibility Loci and Their Role in Survival

被引:44
|
作者
Rizzato, Cosmeri [1 ]
Campa, Daniele [1 ]
Giese, Nathalia [2 ]
Werner, Jens [2 ]
Rachakonda, P. Sivaramakrishna [1 ]
Kumar, Rajiv [1 ]
Schanne, Michaela [1 ]
Greenhalf, William [3 ,4 ]
Costello, Eithne [3 ,4 ]
Khaw, Kay-tee [5 ]
Key, Tim J. [6 ]
Siddiq, Afshan [7 ]
Lorenzo-Bermejo, Justo [8 ]
Burwinkel, Barbara [1 ,9 ]
Neoptolemos, John P. [3 ,4 ]
Buechler, Markus W. [2 ]
Hoheisel, Joerg D. [1 ]
Bauer, Andrea [1 ]
Canzian, Federico [1 ]
机构
[1] German Canc Res Ctr, Heidelberg, Germany
[2] Univ Heidelberg, Clin Gen Visceral & Transplantat Surg, Heidelberg, Germany
[3] Natl Inst Hlth Res, Pancreas Biomed Res Unit, Liverpool, Merseyside, England
[4] Natl Inst Hlth Res, Liverpool Expt Canc Med Ctr, Liverpool, Merseyside, England
[5] Univ Cambridge, Sch Clin Med, Cambridge, England
[6] Univ Oxford, Canc Epidemiol Unit, Oxford, England
[7] Univ London Imperial Coll Sci Technol & Med, London, England
[8] Univ Heidelberg Hosp, Inst Med Biometry & Informat, Heidelberg, Germany
[9] Univ Heidelberg, Dept Gynecol & Obstet, Div Mol Biol Breast Canc, Heidelberg, Germany
来源
PLOS ONE | 2011年 / 6卷 / 11期
关键词
GENOME-WIDE ASSOCIATION; POLYMORPHISMS; ADIPONECTIN; COHORT;
D O I
10.1371/journal.pone.0027921
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Pancreatic cancer has one of the worst mortality rates of all cancers. Little is known about its etiology, particularly regarding inherited risk. The PanScan project, a genome-wide association study, identified several common polymorphisms affecting pancreatic cancer susceptibility. Single nucleotide polymorphisms (SNPs) in ABO, sonic hedgehog (SHH), telomerase reverse transcriptase (TERT), nuclear receptor subfamily 5, group A, member 2 (NR5A2) were found to be associated with pancreatic cancer risk. Moreover the scan identified loci on chromosomes 13q22.1 and 15q14, to which no known genes or other functional elements are mapped. We sought to replicate these observations in two additional, independent populations (from Germany and the UK), and also evaluate the possible impact of these SNPs on patient survival. We genotyped 15 SNPs in 690 cases of pancreatic ductal adenocarcinoma (PDAC) and in 1277 healthy controls. We replicated several associations between SNPs and PDAC risk. Furthermore we found that SNP rs8028529 was weakly associated with a better overall survival (OS) in both populations. We have also found that NR5A2 rs12029406_T allele was associated with a shorter survival in the German population. In conclusion, we found that rs8028529 could be, if these results are replicated, a promising marker for both risk and prognosis for this lethal disease.
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页数:6
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