期刊
GUT
卷 63, 期 1, 页码 152-160出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/gutjnl-2012-303477
关键词
Cancer Genetics; Molecular Epidemiology; Pancreatic Cancer
资金
- NCI [R01CA034588, R01CA098661, P30CA016087]
- National Institute of Environmental Health Sciences [ES000260]
- National Heart, Lung, and Blood Institute, National Institutes of Health
- US Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]
- National Institutes of Health (Bethesda, MD) [CA 97193, CA 34944, CA 40360, HL 26490, HL 34595]
- National Cancer Institute, National Institutes of Health [P01 CA87969, P01 CA55075, P50 CA127003, R01 CA124908]
- American Society of Clinical Oncology Career Development Award
- Howard Hughes Medical Institute Early Career Physician-Scientist Award
- Lustgarten Foundation for Pancreatic Cancer Research
- hanghai Men's Health Study was supported by the National Cancer Institute extramural research grant [R01 CA82729]
- National Cancer Institute extramural research grant [R37 CA70867]
- US Public Health Service [N01-CN-45165, N01-RC-45035, N01-RC-37004, HHSN261201000006C]
- Intramural Research Program of the National Cancer Institute
- National Institute of Aging [5U01AG018033]
- National Cancer Institute [CA105069, CA73790]
- Cancer Research UK [14136] Funding Source: researchfish
- Medical Research Council [G1000143, G0401527] Funding Source: researchfish
- Associazione Italiana per la Ricerca sul Cancro Funding Source: Custom
- DIVISION OF CANCER PREVENTION AND CONTROL [N01CN045165] Funding Source: NIH RePORTER
- NATIONAL CANCER INSTITUTE [P50CA127003, UM1CA173640, ZIACP010193, R01CA082729, R01CA098661, R01CA047988, K07CA073790, R01CA097193, P01CA055075, R01CA034588, P30CA015083, R01CA124908, R01CA105069, R37CA070867, R01CA040360, P01CA087969, P30CA016087, K07CA140790, P30CA015704] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL034595] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [P30ES000260] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [U01AG018033] Funding Source: NIH RePORTER
- WOMEN&apos
- S HEALTH INITIATIVE - OFFICE OF THE DIRECTOR NIH [N01WH022110] Funding Source: NIH RePORTER
Background and objective Survival of patients with pancreatic adenocarcinoma is limited and few prognostic factors are known. We conducted a two-stage genome-wide association study (GWAS) to identify germline variants associated with survival in patients with pancreatic adenocarcinoma. Methods We analysed overall survival in relation to single nucleotide polymorphisms (SNPs) among 1005 patients from two large GWAS datasets, PanScan I and ChinaPC. Cox proportional hazards regression was used in an additive genetic model with adjustment for age, sex, clinical stage and the top four principal components of population stratification. The first stage included 642 cases of European ancestry (PanScan), from which the top SNPs (p10(-5)) were advanced to a joint analysis with 363 additional patients from China (ChinaPC). Results In the first stage of cases of European descent, the top-ranked loci were at chromosomes 11p15.4, 18p11.21 and 1p36.13, tagged by rs12362504 (p=1.63x10(-7)), rs981621 (p=1.65x10(-7)) and rs16861827 (p=3.75x10(-7)), respectively. 131 SNPs with p10(-5) were advanced to a joint analysis with cases from the ChinaPC study. In the joint analysis, the top-ranked SNP was rs10500715 (minor allele frequency, 0.37; p=1.72x10(-7)) on chromosome 11p15.4, which is intronic to the SET binding factor 2 (SBF2) gene. The HR (95% CI) for death was 0.74 (0.66 to 0.84) in PanScan I, 0.79 (0.65 to 0.97) in ChinaPC and 0.76 (0.68 to 0.84) in the joint analysis. Conclusions Germline genetic variation in the SBF2 locus was associated with overall survival in patients with pancreatic adenocarcinoma of European and Asian ancestry. This association should be investigated in additional large patient cohorts.
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