期刊
PANCREAS
卷 47, 期 5, 页码 637-642出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MPA.0000000000001052
关键词
advanced pancreatic cancer; drug response biomarker; genetic polymorphism; SLCO1B1; CI - confidence interval; GEM - gemcitabine; GS - gemcitabine plus S-1; GWAS - genome-wide association study; HR - hazard ratio; MST - median survival time; MTX - methotrexate; OS - overall survival; PC - pancreatic cancer; SLCO1B1-solute carrier organic anion transporter family member 1B1; SNPs - single-nucleotide polymorphisms
资金
- National Institute of Biomedical Innovation
- National Cancer Center Research Projects Management expenses
- Japan Society for the Promotion of Science [26870099]
- Taiho Pharmaceutical
- Eli Lilly
- Chugai
- Oncotherapy Science
- Yakult
- Abbott
- Amgen
- Bayer
- Pfizer
- Grants-in-Aid for Scientific Research [26870099] Funding Source: KAKEN
Objectives The aim of this study was to evaluate the effects of single-nucleotide polymorphisms (SNPs) on advanced pancreatic cancer risk and overall survival (OS) in a candidate-gene approach. Methods Overall, 5438 SNPs in 219 candidate genes encoding several drug-metabolizing enzymes or transporters were analyzed. In the screening study, 3 SNPs were found associated with OS (P 0.0005). We validated these SNPs as part of the randomized phase 3 study (GEST study). The associations between OS and SNPs were investigated using log-rank test and Cox proportional hazards model. Results From the GEST study, the SNP rs4149086 in the 3 UTR of the solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene showed significant interaction with treatment (P = 0.02). In the gemcitabine group, the SNP was associated with short OS (hazard ratio [HR], 3.75; 95% confidence interval [CI], 1.30-10.8; P = 0.008) even after multiple-comparisons adjustment. In contrast, the SNP was not associated with OS in S-1 (HR, 0.77; 95% CI, 0.33-1.81; P = 0.55) or gemcitabine plus S-1 groups (HR, 1.18; 95% CI, 0.46-3.00; P = 0.72). Conclusions Patients with advanced pancreatic cancer with the rs4149086 AG or GG genotype may obtain good clinical results when treated with S-1-containing regimens.
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