title: Identification of common variants in BRCA2 and MAP2K4 for susceptibility to sporadic pancreatic cancer.
abstract: Germline mutations in genes that cause hereditary syndromes are highly predisposed to familial pancreatic cancer. However, genetic susceptibility to sporadic pancreatic cancer is largely uncovered. We conducted a two-stage association study on pancreatic cancer that included 981 cases and 1991 controls in the first stage followed by a second stage (2603 cases and 2877 controls). Using an approach based on candidate genes whose roles in pancreatic cancer have been well known, we identified two new susceptibility loci. rs11571836 located in the BRCA2 3'-untranslated region was significantly associated with lower expression of BRCA2 transcript and increased pancreatic cancer risk [odds ratio = 1.30, 95% confidence interval = 1.14-1.47, P = 7.64 × 10(-5)] in a recessive manner. rs12939944 located in the MAP2K4 intron was associated with decreased risk (odds ratio = 0.82, 95% confidence interval = 0.74-0.91, P = 0.0001) in a dominant manner. Our results demonstrate for the first time that common variants in BRCA2 and MAP2K4 are susceptibility to sporadic pancreatic cancer.
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Liming
authors.initials: L
authors.lastname: Huang
authors.forename: Chen
authors.initials: C
authors.lastname: Wu
authors.forename: Dianke
authors.initials: D
authors.lastname: Yu
authors.forename: Chengfeng
authors.initials: C
authors.lastname: Wang
authors.forename: Xu
authors.initials: X
authors.lastname: Che
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Miao
authors.forename: Kan
authors.initials: K
authors.lastname: Zhai
authors.forename: Jiang
authors.initials: J
authors.lastname: Chang
authors.forename: Guoliang
authors.initials: G
authors.lastname: Jiang
authors.forename: Xianghong
authors.initials: X
authors.lastname: Yang
authors.forename: Guangwen
authors.initials: G
authors.lastname: Cao
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Zhou
authors.forename: Chaohui
authors.initials: C
authors.lastname: Zuo
authors.forename: Chunyou
authors.initials: C
authors.lastname: Wang
authors.forename: Xianghong
authors.initials: X
authors.lastname: Zhang
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Zhou
authors.forename: Xianjun
authors.initials: X
authors.lastname: Yu
authors.forename: Wanjin
authors.initials: W
authors.lastname: Dai
authors.forename: Zhaoshen
authors.initials: Z
authors.lastname: Li
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
authors.forename: Luming
authors.initials: L
authors.lastname: Liu
authors.forename: Yanling
authors.initials: Y
authors.lastname: Chen
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Menghong
authors.initials: M
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.forename: Jun
authors.initials: J
authors.lastname: Gao
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Zheng
authors.forename: Siu Tim
authors.initials: ST
authors.lastname: Cheung
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Jia
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
authors.forename: Tangchun
authors.initials: T
authors.lastname: Wu
authors.forename: Dongxin
authors.initials: D
authors.lastname: Lin
mesh_terms: D020413:3' Untranslated Regions; D024682:BRCA2 Protein / Q000235:genetics*; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D007438:Introns; D048670:MAP Kinase Kinase 4 / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide
chemical_list: D020413:3' Untranslated Regions; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D048670:MAP Kinase Kinase 4; C482559:MAP2K4 protein, human