Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer.
Wolpin BM., Rizzato C., Kraft P., Kooperberg C., Petersen GM., Wang Z., Arslan AA., Beane-Freeman L., Bracci PM., Buring J., Canzian F., Duell EJ., Gallinger S., Giles GG., Goodman GE., Goodman PJ., Jacobs EJ., Kamineni A., Klein AP., Kolonel LN., Kulke MH., Li D., Malats N., Olson SH., Risch HA., Sesso HD., Visvanathan K., White E., Zheng W., Abnet CC., Albanes D., Andreotti G., Austin MA., Barfield R., Basso D., Berndt SI., Boutron-Ruault M-C., Brotzman M., Büchler MW., Bueno-de-Mesquita HB., Bugert P., Burdette L., Campa D., Caporaso NE., Capurso G., Chung C., Cotterchio M., Costello E., Elena J., Funel N., Gaziano JM., Giese NA., Giovannucci EL., Goggins M., Gorman MJ., Gross M., Haiman CA., Hassan M., Helzlsouer KJ., Henderson BE., Holly EA., Hu N., Hunter DJ., Innocenti F., Jenab M., Kaaks R., Key TJ., Khaw K-T., Klein EA., Kogevinas M., Krogh V., Kupcinskas J., Kurtz RC., LaCroix A., Landi MT., Landi S., Le Marchand L., Mambrini A., Mannisto S., Milne RL., Nakamura Y., Oberg AL., Owzar K., Patel AV., Peeters PHM., Peters U., Pezzilli R., Piepoli A., Porta M., Real FX., Riboli E., Rothman N., Scarpa A., Shu X-O., Silverman DT., Soucek P., Sund M., Talar-Wojnarowska R., Taylor PR., Theodoropoulos GE., Thornquist M., Tjønneland A., Tobias GS., Trichopoulos D., Vodicka P., Wactawski-Wende J., Wentzensen N., Wu C., Yu H., Yu K., Zeleniuch-Jacquotte A., Hoover R., Hartge P., Fuchs C., Chanock SJ., Stolzenberg-Solomon RS., Amundadottir LT.
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 × 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 × 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 × 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 × 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 × 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 × 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.