4.8 Article

Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer

Journal

NATURE GENETICS
Volume 46, Issue 9, Pages 994-+

Publisher

NATURE PORTFOLIO
DOI: 10.1038/ng.3052

Keywords

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Funding

  1. National Cancer Institute (NCI), US National Institutes of Health (NIH) [HHSN261200800001E]
  2. NIH/NCI [K07 CA140790]
  3. American Society of Clinical Oncology Conquer Cancer Foundation
  4. Howard Hughes Medical Institute
  5. Lustgarten Foundation
  6. Cancer Research UK [16491, 14136] Funding Source: researchfish
  7. Medical Research Council [G0401527, G1000143] Funding Source: researchfish
  8. National Institute for Health Research [NF-SI-0512-10114] Funding Source: researchfish

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We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.84, P = 3.0 x 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 x 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 x 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 x 10(-8)). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76-0.85, P = 9.8 x 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 x 10(-7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies.

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