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Genetic polymorphisms in the 9p21 region associated with risk of multiple cancers.

Authors :
Li, Wen-Qing
Pfeiffer, Ruth M.
Hyland, Paula L.
Shi, Jianxin
Gu, Fangyi
Wang, Zhaoming
Bhattacharjee, Samsiddhi
Luo, Jun
Xiong, Xiaoqin
Yeager, Meredith
Deng, Xiang
Hu, Nan
Taylor, Philip R.
Albanes, Demetrius
Caporaso, Neil E.
Gapstur, Susan M.
Amundadottir, Laufey
Chanock, Stephen J.
Chatterjee, Nilanjan
Landi, Maria Teresa
Source :
Carcinogenesis. Dec2014, Vol. 35 Issue 12, p2698-2705. 8p.
Publication Year :
2014

Abstract

We systematically examined common genetic variants in the 9p21 region and risk of eight cancers, based on GWAS data deposited in dbGaP. A number of SNPs were associated with multiple cancers, which are not confined to the CDKN2/MTAP cluster.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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
01433334
Volume :
35
Issue :
12
Database :
Academic Search Index
Journal :
Carcinogenesis
Publication Type :
Academic Journal
Accession number :
99750533