Dataset Information

Association of Common Susceptibility Variants of Pancreatic Cancer in Higher-Risk Patients: A PACGENE Study.

ABSTRACT: 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 early-onset 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 × 10(-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 < 5 × 10(-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. Cancer Epidemiol Biomarkers Prev; 25(7); 1185-91. ©2016 AACR.

SUBMITTER: Childs EJ

PROVIDER: S-EPMC5321211 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Association of Common Susceptibility Variants of Pancreatic Cancer in Higher-Risk Patients: A PACGENE Study.

Childs Erica J EJ Chaffee Kari G KG Gallinger Steven S Syngal Sapna S Schwartz Ann G AG Cote Michele L ML Bondy Melissa L ML Hruban Ralph H RH Chanock Stephen J SJ Hoover Robert N RN Fuchs Charles S CS Rider David N DN Amundadottir Laufey T LT Stolzenberg-Solomon Rachael R Wolpin Brian M BM Risch Harvey A HA Goggins Michael G MG Petersen Gloria M GM Klein Alison P AP

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20160516 7

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 5 ...[more]

PMID: 27197284

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Project description:Background:Women with unilateral breast cancer (UBC) are at risk of developing a subsequent contralateral breast cancer (CBC). Common variants are associated with breast cancer risk. Whether these influence CBC risk is unknown. Methods:Participants were breast cancer cases from the population-based Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study. Sixty-seven established breast cancer risk loci were genotyped directly or by imputation in 1459 case subjects with CBC and 2126 UBC control subjects. An unweighted polygenic risk score (PRS) was created by summing the number of risk alleles for each directly genotyped single nucleotide polymorphism (SNP), or for imputed loci, the imputed dosage. A weighted PRS was calculated similarly, but where each SNP's contribution was weighted by the published per-allele log odds ratio. Unweighted and weighted polygenic risk scores and CBC risk were modeled using conditional logistic regression. Cumulative CBC risk was estimated and benchmarked using Surveillance, Epidemiology, and End Results population incidence rates. Results:Both unweighted and weighted PRS were statistically significantly associated with CBC risk. The adjusted risk ratio of CBC in women in the upper quartile of unweighted PRS compared with the lowest quartile was 1.63 (95% confidence interval [CI] = 1.33 to 2.00). The estimated 10-year cumulative risk for women in the upper quartile of the unweighted PRS was 7.4% (95% CI?=?6.0% to 9.1%). For women in the upper quartile of the weighted PRS, the risk ratio for CBC was 1.75 (95% CI?=?1.41 to 2.18) compared with women in the lowest quartile. There was no statistically significant heterogeneity by age, treatment (radiation therapy dose, tamoxifen, chemotherapy), estrogen receptor status of the first primary, histology of the first primary, length of at-risk period for CBC, or breast cancer family history. Conclusions:Common genomic variants associated with the development of first primary breast cancer are also associated with the development of CBC; the risk is strongest among those who carry more risk alleles.

Dataset Information

Association of Common Susceptibility Variants of Pancreatic Cancer in Higher-Risk Patients: A PACGENE Study.

Publications

Association of Common Susceptibility Variants of Pancreatic Cancer in Higher-Risk Patients: A PACGENE Study.

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