Association of common susceptibility variants of pancreatic cancer in higher risk patients: A PACGENE study
Menée aux Etats-Unis à partir de données portant sur 985 cas et 877 témoins, cette étude analyse l'association entre des variants génétiques précédemment associés au risque de cancer du pancréas, du sein, de l'ovaire ou de la prostate, et le risque de cancer du pancréas chez une population à haut risque (histoire familiale ou apparition précoce de la maladie)
Individuals from pancreatic cancer families are at increased risk, not only of pancreatic cancer, but also of melanoma, breast, ovarian, and colon cancers. While some of the increased risk may be due to mutations in high-penetrance genes (i.e. BRCA2, PALB2, ATM, p16/CDKN2A or DNA mismatch-repair genes), common genetic variants may also be involved. In a high-risk population of cases with either a family history of pancreatic cancer or early-onset pancreatic cancer (diagnosis before age 50), we examined the role of genetic variants previously associated with risk of pancreatic, breast, ovarian, or prostate cancer. We genotyped 985 cases (79 early-onset cases, 906 cases with a family history of pancreatic cancer) and 877 controls for 215,389 SNPs using the iCOGS array with custom content. Logistic regression was performed using a log-linear additive model. We replicated several previously reported pancreatic cancer susceptibility loci, including recently identified variants on 2p13.3 and 7p13 (2p13.3, rs1486134: OR=1.36, 95%CI (1.13-1.63), p=9.29X10-4; 7p13, rs17688601: OR =0.76, 95%CI (0.63-0.93), p=6.59X10-3). For the replicated loci, the magnitude of association observed in these high-risk patients was similar to that observed in studies of unselected patients. In addition to the established pancreatic cancer loci, we also found suggestive evidence of association (p<5x10-5) to pancreatic cancer for SNPs at HDAC9 (7p21.1) and COL6A2 (21q22.3). Even in high-risk populations, common variants influence pancreatic cancer susceptibility.