Genome-wide association study identifies five loci associated with susceptibility to pancreatic cancer in Chinese populations

Abstract

Pancreatic cancer has the lowest survival rate among human cancers, and there are no effective markers for its screening and early diagnosis. To identify genetic susceptibility markers for this cancer, we carried out a genome-wide association study on 981 individuals with pancreatic cancer (cases) and 1,991 cancer-free controls of Chinese descent using 666,141 autosomal SNPs. Promising associations were replicated in an additional 2,603 pancreatic cancer cases and 2,877 controls recruited from 25 hospitals in 16 provinces or cities in China. We identified five new susceptibility loci at chromosomes 21q21.3, 5p13.1, 21q22.3, 22q13.32 and 10q26.11 (P = 2.24 × 10(-13) to P = 4.18 × 10(-10)) in addition to 13q22.1 previously reported in populations of European ancestry. These results advance our understanding of the development of pancreatic cancer and highlight potential targets for the prevention or treatment of this cancer.

A cross-platform analysis of 14,177 expression quantitative trait loci derived from lymphoblastoid cell lines

“…This is more than six times larger than our previous eQTL database , which has been used to identify association with expression for SNPs associated with asthma ), Crohn's disease (Libioulle et al 2007), and type 1 diabetes (Plagnol et al 2009). Even before publication, our two newly developed eQTL databases have been used to interpret findings from large-scale GWAS, including human height (Lango Allen et al 2010), body mass index , waisthip ratio (Heid et al 2010), osteoporosis-related traits (Hsu et al 2010), Graves' disease (Chu et al 2011), pancreatic cancer (Wu et al 2012), and pathways associated with basal cell skin carcinoma (Zhang et al 2012). Our systematic investigation of the GWAS database presented in Supplemental Table 3 suggests that eQTL analyses may add to the understanding of many other loci mapped for complex genetic diseases.…”

Leukocyte Telomere Length in Relation to Pancreatic Cancer Risk: A Prospective Study

“…Established risk factors for pancreas cancer are cigarette smoking, heavy alcohol consumption, preexisting diabetes mellitus (diagnosed at least 3 years before diagnosis of pancreatic cancer), obesity, chronic pancreatitis, and family history of pancreatic cancer (3,4). In addition, elevated fasting blood glucose levels (also within the nondiabetic range) and a small number of genetic polymorphic variants have been related to an increased risk (3,(5)(6)(7)(8)(9)(10)(11). Overall, however, these known risk factors can account for only a modest proportion of pancreas cancer occurrences, and taken together, they can provide only a very weak prediction of an individual's pancreas cancer risk.…”

ABO blood groups and pancreatic cancer risk and survival: Results from the PANcreatic Disease ReseArch (PANDoRA) consortium

“…Three genomewide association studies have been performed and resulted in several loci convincingly being associated with risk of pancreatic cancer (6)(7)(8)(9). In particular, there is increasing evidence of the involvement of the ABO gene variability and pancreatic cancer risk (6,(10)(11)(12).…”