The Cumulative Effect of Gene-Gene and Gene-Environment Interactions on the Risk of Prostate Cancer in Chinese Men.
The Cumulative Effect of Gene-Gene and Gene-Environment Interactions on the Risk of Prostate Cancer in Chinese Men.
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DOI：
10.3390/ijerph13020162
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发表时间：
2016-01-27
影响因子：
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通讯作者：
Yang Z
中科院分区：
文献类型：
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作者：
Liu M;Shi X;Yang F;Wang J;Xu Y;Wei D;Yang K;Zhang Y;Wang X;Liang S;Chen X;Sun L;Zhu X;Zhao C;Zhu L;Tang L;Zheng C;Yang Z
前列腺癌（PCa）是一种多因素疾病，涉及复杂的遗传和环境因素相互作用。与中国男性前列腺癌相关的基因-基因和基因-环境相互作用研究较少。我们研究了来自中国北方574名受试者的36个snp与PCa之间的关系。通过对134例PCa患者进行自我管理的问卷调查，确定了他们的身体质量指数（BMI）、吸烟和饮酒情况。采用广义多因素降维（GMDR）和逻辑回归分析了pca相关snp之间的基因-基因和基因-环境相互作用。等位基因和基因型关联分析显示，6种变异与PCa相关，累积效应表明，携带1、2或≥3种风险基因型的男性患PCa的风险逐渐增加（优势比(or) = 1.79-4.41）。GMDR分析确定了交叉验证一致性和符号测试得分为10分的最佳基因-基因相互作用模型。对于基因-环境相互作用，BMI≥28个体rs6983561 CC和rs16901966 GG的or值分别为7.66 （p = 0.032）和5.33 （p = 0.046）。吸烟个体rs7679673 CC + CA和rs12653946 TT的or值分别为2.77 （p = 0.007）和3.11 （p = 0.024）。饮酒个体rs7679673 CC的OR为4.37 （p = 0.041）。这些结果表明，多态性，无论是单独的还是与其他基因或环境因素相互作用，都有助于增加PCa的风险。
Prostate cancer (PCa) is a multifactorial disease involving complex genetic and environmental factors interactions. Gene-gene and gene-environment interactions associated with PCa in Chinese men are less studied. We explored the association between 36 SNPs and PCa in 574 subjects from northern China. Body mass index (BMI), smoking, and alcohol consumption were determined through self-administered questionnaires in 134 PCa patients. Then gene-gene and gene-environment interactions among the PCa-associated SNPs were analyzed using the generalized multifactor dimensionality reduction (GMDR) and logistic regression methods. Allelic and genotypic association analyses showed that six variants were associated with PCa and the cumulative effect suggested men who carried any combination of 1, 2, or ≥3 risk genotypes had a gradually increased PCa risk (odds ratios (ORs) = 1.79–4.41). GMDR analysis identified the best gene-gene interaction model with scores of 10 for both the cross-validation consistency and sign tests. For gene-environment interactions, rs6983561 CC and rs16901966 GG in individuals with a BMI ≥ 28 had ORs of 7.66 (p = 0.032) and 5.33 (p = 0.046), respectively. rs7679673 CC + CA and rs12653946 TT in individuals that smoked had ORs of 2.77 (p = 0.007) and 3.11 (p = 0.024), respectively. rs7679673 CC in individuals that consumed alcohol had an OR of 4.37 (p = 0.041). These results suggest that polymorphisms, either individually or by interacting with other genes or environmental factors, contribute to an increased risk of PCa.