Environmental factors, seven GWAS-identified susceptibility loci, and risk of gastric cancer and its precursors in a Chinese population.
Environmental factors, seven GWAS-identified susceptibility loci, and risk of gastric cancer and its precursors in a Chinese population.
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中国人群的环境因素、GWAS确定的7个易感位点以及胃癌及其癌前病变的风险
DOI：
10.1002/cam4.1038
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发表时间：
2017-03
期刊：
影响因子：
4
通讯作者：
Zhao X
中科院分区：
文献类型：
--
作者：
Cai M;Dai S;Chen W;Xia C;Lu L;Dai S;Qi J;Wang M;Wang M;Zhou L;Lei F;Zuo T;Zeng H;Zhao X
基因-环境相互作用可能增加胃癌（GC）的风险。全基因组关联研究（GWAS）确定的7个易感基因座表明遗传因素在胃癌发生中起作用。同时，幽门螺杆菌（H. pylori）感染、吸烟、饮酒也是胃癌发生的重要环境因素。然而，研究探讨基因-环境相互作用在胃癌发生中的作用，特别是7个易感基因座之间的关系及其与幽门螺杆菌感染、吸烟和饮酒的潜在相互作用在GC和严重肠上皮化生（IM）/异型增生的风险中的作用，尚未得出结论。在中国人群中共招募了1273例受试者，并使用竞争性等位基因特异性PCR（KASP）方法进行基因分型。应用非条件Logistic回归分析基因多态性与疾病风险之间的关系。幽门螺杆菌感染，吸烟和饮酒的影响进行了评估。PSCA rs 2294008/rs 2976392与幽门螺杆菌感染在GC风险方面表现出显著的倍增相互作用。PRKAA 1 rs 13361707与H. pylori感染之间存在加性相互作用。SLC 52 A3 rs 13042395与饮酒在GC风险中存在相互作用。此外，MUC 1 rs 4072037、ZBTB 20 rs 9841504和PRKAA 1 rs 13361707这三个SNP与胃癌前病变（严重IM/异型增生）相关。我们的数据表明，GWAS确定的遗传易感因素可能与环境危险因素相互作用，特别是幽门螺杆菌感染和饮酒，以增加GC的风险。
Gene–environment interactions may increase gastric cancer (GC) risk. Seven susceptibility loci identified by genome‐wide association studies (GWASs) suggest that genetic factors play a role in gastric carcinogenesis. Meanwhile, Helicobacter pylori (H. pylori) infection, smoking, and alcohol drinking are also important environmental factors for gastric cancer. However, studies to explore the role of gene–environment interactions in gastric carcinogenesis, and particularly the relationship between the seven susceptibility loci and their potential interactions with H. pylori infection, smoking, and alcohol drinking in risk of GC, and severe intestinal metaplasia (IM)/dysplasia, have been inconclusive. A total of 1273 subjects in a Chinese population were recruited, and genotyping was carried out using the competitive allele‐specific PCR (KASP) method. Unconditional logistic regression was applied to model the associations between genetic polymorphisms and the disease risk. Effect modifications by H. pylori infection, smoking and alcohol drinking were evaluated. PSCA rs2294008/rs2976392 showed a significant, multiplicative interaction with H. pylori infection in risk of GC. Meanwhile, PRKAA1 rs13361707 had an additive interaction with H. pylori infection. SLC52A3 rs13042395 showed an interaction with alcohol drinking in risk of GC. Moreover, three SNPs, MUC1 rs4072037, ZBTB20 rs9841504 and PRKAA1 rs13361707, were associated with precancerous gastric lesions (severe IM/dysplasia). Our data suggest that genetic predisposition factors identified by GWAS may interact with environmental risk factors, Particularly for H. pylori infection and alcohol consumption, to increase the risk of GC.