| Literature DB >> 25239644 |
Wen-Qing Li1, Ruth M Pfeiffer2, Paula L Hyland2, Jianxin Shi2, Fangyi Gu2, Zhaoming Wang3, Samsiddhi Bhattacharjee4, Jun Luo5, Xiaoqin Xiong6, Meredith Yeager3, Xiang Deng3, Nan Hu2, Philip R Taylor2, Demetrius Albanes2, Neil E Caporaso2, Susan M Gapstur7, Laufey Amundadottir2, Stephen J Chanock2, Nilanjan Chatterjee2, Maria Teresa Landi2, Margaret A Tucker2, Alisa M Goldstein2, Xiaohong R Yang2.
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. Published by Oxford University Press 2014.Entities:
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Year: 2014 PMID： 25239644 PMCID： PMC4247519 DOI： 10.1093/carcin/bgu203
Source DB: PubMed Journal: Carcinogenesis ISSN： 0143-3334 Impact factor: 4.944