TY - JOUR
T1 - Association of common susceptibility variants of pancreatic cancer in higher-risk patients
T2 - A PACGENE study
AU - Childs, Erica J.
AU - Chaffee, Kari G.
AU - Gallinger, Steven
AU - Syngal, Sapna
AU - Schwartz, Ann G.
AU - Cote, Michele L.
AU - Bondy, Melissa L.
AU - Hruban, Ralph H.
AU - Chanock, Stephen J.
AU - Hoover, Robert N.
AU - Fuchs, Charles S.
AU - Rider, David N.
AU - Amundadottir, Laufey T.
AU - Stolzenberg-Solomon, Rachael
AU - Wolpin, Brian M.
AU - Risch, Harvey A.
AU - Goggins, Michael G.
AU - Petersen, Gloria M.
AU - Klein, Alison P.
N1 - Funding Information:
This work was supported by NIH grants R01 CA97075 (to K.G. Chaffee, S. Gallinger, S. Syngal, A.G. Schwartz, M.L. Cote, R.H. Hruban, D.N. Rider, M.G. Goggins, G.M. Petersen, and A.P. Klein) and R01 CA154823 (to E.J. Childs, K.G. Chaffee, S. Gallinger, H.A. Risch, M.G. Goggins, G.M. Petersen, and A.P. Klein) and NIH Specialized Programs of Research Excellence P50 CA062924 (to R.H. Hruban, M.G. Goggins, A.P. Klein) and P50 CA102701 (K.G. Chaffee, D.N. Rider, G.M. Petersen), the Lustgarten Foundation for Pancreatic Cancer Research (to R.H. Hruban, M.G. Goggins, A.P. Klein), the Michael Rolfe Foundation (to R.H. Hruban, M.G. Goggins), Susan Wojcicki and Dennis Troper (to R.H. Hruban, M.G. Goggins, A.P. Klein), and the Sol Goldman Pancreatic Cancer Research Center (to R.H. Hruban, M.G. Goggins, A.P. Klein). B.M. Wolpin was supported by NIH under grant no. K07 CA140790. The development of the iCOGS array was supported by the European Community's Seventh Framework Programme under grant agreement 223175 (HEALTHF22009223175) and Cancer Research UK (C1287/A10710)
Publisher Copyright:
© 2016 American Association for Cancer Research.
PY - 2016/7
Y1 - 2016/7
N2 - 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 the age of 50 years), we examined the role of genetic variants previously associated with risk of pancreatic, breast, ovarian, or prostate cancer. We genotyped 985 cases (79 earlyonset cases, 906 cases with a family history of pancreatic cancer) and 877 controls for 215,389 SNPs using the iSelect Collaborative Oncological Gene-Environment Study (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 = 9.29 × 10-4; 7p13, rs17688601: OR = 0.76; 95%CI, 0.63-0.93; P=6.59 × 103). 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 < 5 × 105) to pancreatic cancer for SNPs atHDAC9(7p21.1) and COL6A2 (21q22.3). Even in high-risk populations, common variants influence pancreatic cancer susceptibility.
AB - 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 the age of 50 years), we examined the role of genetic variants previously associated with risk of pancreatic, breast, ovarian, or prostate cancer. We genotyped 985 cases (79 earlyonset cases, 906 cases with a family history of pancreatic cancer) and 877 controls for 215,389 SNPs using the iSelect Collaborative Oncological Gene-Environment Study (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 = 9.29 × 10-4; 7p13, rs17688601: OR = 0.76; 95%CI, 0.63-0.93; P=6.59 × 103). 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 < 5 × 105) to pancreatic cancer for SNPs atHDAC9(7p21.1) and COL6A2 (21q22.3). Even in high-risk populations, common variants influence pancreatic cancer susceptibility.
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U2 - 10.1158/1055-9965.EPI-15-1217
DO - 10.1158/1055-9965.EPI-15-1217
M3 - Article
C2 - 27197284
AN - SCOPUS:84977111336
SN - 1055-9965
VL - 25
SP - 1185
EP - 1191
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 7
ER -