Associations between variants of the 8q24 chromosome and nine smoking-related cancer sites.
Associations between variants of the 8q24 chromosome and nine smoking-related cancer sites.
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DOI：
10.1158/1055-9965.epi-08-0523
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发表时间：
2008-11
期刊：
影响因子：
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通讯作者：
Zhang ZF
中科院分区：
文献类型：
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作者：
Park SL;Chang SC;Cai L;Cordon-Cardo C;Ding BG;Greenland S;Hussain SK;Jiang Q;Liu S;Lu ML;Mao JT;Morgenstern H;Mu LN;Ng LJ;Pantuck A;Rao J;Reuter VE;Tashkin DP;You NC;Yu CQ;Yu SZ;Zhao JK;Belldegrun A;Zhang ZF
最近的全基因组关联（GWA）研究确定了8q24区域中与前列腺癌相关的关键单核苷酸多态性（SNP）。8q24 SNP也与结直肠癌相关，这表明该区域可能不仅仅与前列腺癌相关。迄今为止，这些多态性与吸烟相关癌症部位之间的关联仍然未知。使用流行病学数据和先前在美国和中国人群的三个病例对照研究中收集的生物样本，我们从8q24基因座内先前确定的三个“区域”中的每一个中选择一个SNP并进行基因分型：rs1447295（区域1），rs16901979（区域2）和rs6983267（区域3），并检查其与肺癌、口咽癌、鼻咽癌、喉癌、食道癌、胃癌、肝癌、膀胱癌和肾癌的相关性。我们观察到rs6983267与上呼吸消化道（UADT）癌症（ORadj=1.69，95%CI =1.28，2.24）之间存在显著相关性，特别是口咽（ORadj=1.80，95%CI =1.30，2.49）和喉（ORadj=2.04，95%CI =1.12，3.72）。我们还观察到rs6983267与肝癌之间的暗示性关联（ORadj=1.51，95%CI =0.99，2.31）。当我们按吸烟状态对分析进行分层时，rs 6983267与曾经吸烟者的肺癌正相关（ORadj=1.45，95%CI =1.05，2.00），与曾经吸烟者的膀胱癌负相关（ORadj=0.35，95%CI =0.14，0.83）。在从不吸烟者中观察到rs16901979与UADT癌症之间的关联，在曾经吸烟者中观察到rs1447295与肝癌之间的关联。我们的研究结果表明，8q24染色体的变异可能在吸烟相关的癌症发展中发挥重要作用。应进行功能性和大型流行病学研究，以进一步研究8q24 SNP与吸烟相关癌症的关联。
Recent genome-wide association (GWA) studies identified key single nucleotide polymorphisms (SNPs) in the 8q24 region to be associated with prostate cancer. 8q24 SNPs have also been associated with colorectal cancer, suggesting this region may not be specifically associated to just prostate cancer. To date, the association between these polymorphisms and tobacco smoking-related cancer sites remains unknown. Using epidemiological data and biological samples previously collected in three case-control studies from U.S. and Chinese populations, we selected and genotyped one SNP from each of the three previously determined “regions” within the 8q24 loci: rs1447295 (region 1), rs16901979 (region 2), and rs6983267 (region 3), and examined their association with cancers of the lung, oropharynx, nasopharynx, larynx, esophagus, stomach, liver, bladder, and kidney. We observed noteworthy associations between rs6983267 and upper aero-digestive tract (UADT) cancers (ORadj=1.69, 95% CI=1.28, 2.24), particularly in oropharynx (ORadj=1.80, 95% CI=1.30, 2.49) and larynx (ORadj=2.04, 95% CI=1.12, 3.72). We also observed a suggestive association between rs6983267 and liver cancer (ORadj=1.51, 95% CI=0.99, 2.31). When we stratified our analysis by smoking status, rs6983267 was positively associated with lung cancer among ever-smokers (ORadj=1.45, 95% CI=1.05, 2.00) and inversely associated with bladder cancer among ever-smokers (ORadj=0.35, 95% CI=0.14, 0.83). Associations were observed between rs16901979 and UADT cancer among never-smokers, and between rs1447295 and liver cancer among ever-smokers. Our results suggest variants of the 8q24 chromosome may play an important role in smoking-related cancer development. Functional and large epidemiological studies should be conducted to further investigate the association of 8q24 SNPs with smoking-related cancers.