title: Genetic polymorphisms in the 9p21 region associated with risk of multiple cancers.
abstract: The chromosome 9p21 region has been implicated in the pathogenesis of multiple cancers. We analyzed 9p21 single nucleotide polymorphisms (SNPs) from eight genome-wide association studies (GWAS) with data deposited in dbGaP, including studies of esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), pancreatic cancer, renal cell carcinoma (RCC), lung cancer (LC), breast cancer (BrC), bladder cancer (BC) and prostate cancer (PrC). The number of subjects ranged from 2252 (PrC) to 7619 (LC). SNP-level analyses for each cancer were conducted by logistic regression or random-effects meta-analysis. A subset-based statistical approach (ASSET) was performed to combine SNP-level P values across multiple cancers. We calculated gene-level P values using the adaptive rank truncated product method. We identified that rs1063192 and rs2157719 in the CDKN2A/2B region were significantly associated with ESCC and rs2764736 (3' of TUSC1) was associated with BC (P ≤ 2.59 × 10(-6)). ASSET analyses identified four SNPs significantly associated with multiple cancers: rs3731239 (CDKN2A intronic) with ESCC, GC and BC (P = 3.96 × 10(-) (4)); rs10811474 (3' of IFNW1) with RCC and BrC (P = 0.001); rs12683422 (LINGO2 intronic) with RCC and BC (P = 5.93 × 10(-) (4)) and rs10511729 (3' of ELAVL2) with LC and BrC (P = 8.63 × 10(-) (4)). At gene level, CDKN2B, CDKN2A and CDKN2B-AS1 were significantly associated with ESCC (P ≤ 4.70 × 10(-) (5)). Rs10511729 and rs10811474 were associated with cis-expression of 9p21 genes in corresponding cancer tissues in the expression quantitative trait loci analysis. In conclusion, we identified several genetic variants in the 9p21 region associated with the risk of multiple cancers, suggesting that this region may contribute to a shared susceptibility across different cancer types.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA, Department of Dermatology, Warren Alpert Medical School, Brown University, Providence, RI, USA, wen-qing_li@brown.edu.
authors.forename: Wen-Qing
authors.initials: WQ
authors.lastname: Li
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA.
authors.forename: Paula L
authors.initials: PL
authors.lastname: Hyland
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Shi
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA.
authors.forename: Fangyi
authors.initials: F
authors.lastname: Gu
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA, Cancer Genomics Research Laboratory, NCI-Frederick, SAIC-Frederick Inc., Frederick, MD, USA.
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Wang
authors.affiliation: National Institute of Biomedical Genomics, Kalyani, India.
authors.forename: Samsiddhi
authors.initials: S
authors.lastname: Bhattacharjee
authors.affiliation: Information Management Services, Inc., Calverton, MD, USA and.
authors.forename: Jun
authors.initials: J
authors.lastname: Luo
authors.affiliation: Information Management Services, Inc., Calverton, MD, USA and wen-qing_li@brown.edu royang@mail.nih.gov.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Xiong
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA, Cancer Genomics Research Laboratory, NCI-Frederick, SAIC-Frederick Inc., Frederick, MD, USA.
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA, Cancer Genomics Research Laboratory, NCI-Frederick, SAIC-Frederick Inc., Frederick, MD, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Deng
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA.
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Caporaso
authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gapstur
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA.
authors.forename: Laufey
authors.initials: L
authors.lastname: Amundadottir
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA.
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Chatterjee
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Landi
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Tucker
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA.
authors.forename: Alisa M
authors.initials: AM
authors.lastname: Goldstein
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, Bethesda, MD, USA.
authors.forename: Xiaohong R
authors.initials: XR
authors.lastname: Yang
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D040641:Quantitative Trait Loci; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor