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首页> 外文期刊>Journal of Cachexia, Sarcopenia and Muscle >Body mass index change in gastrointestinal cancer and chronic obstructive pulmonary disease is associated with Dedicator of Cytokinesis 1
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Body mass index change in gastrointestinal cancer and chronic obstructive pulmonary disease is associated with Dedicator of Cytokinesis 1

机译：胃肠道癌和慢性阻塞性肺疾病中的体重指数变化与细胞分裂1有关

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Abstract Background There have been a number of candidate gene association studies of cancer cachexia-related traits, but no genome-wide association study (GWAS) has been published to date. Cachexia presents in patients with a number of complex traits, including both cancer and COPD. The objective of the current investigation was to search for a shared genetic aetiology for change in body mass index (????BMI) among cancer and COPD by using GWAS data in the Framingham Heart Study. Methods A linear mixed effects model accounting for age, sex, and change in smoking status was used to calculate ????BMI in participants over 40 years of age with three consecutive BMI time points ( n = 4162). Four GWAS of ????BMI using generalized estimating equations were performed among 1085 participants with a cancer diagnosis, 204 with gastrointestinal (GI) cancer, 112 with lung cancer, and 237 with COPD to test for association with 418 365 single-nucleotide polymorphisms (SNPs). Results Two SNPs reached a level of genome-wide significance ( P < 5 ???? 10 ?￠????8 ) with ????BMI: (i) rs41526344 within the CNTN4 gene, among COPD cases ( ???2 = 0.13, P = 4.3 ???? 10 ?￠????8 ); and (ii) rs4751240 in the gene Dedicator of Cytokinesis 1 ( DOCK1 ) among GI cancer cases ( ???2 = 0.10, P = 1.9 ???? 10 ?￠????8 ). The DOCK1 SNP association replicated in the ????BMI GWAS among COPD cases ( ???2 meta-analyis = 0.10, P meta-analyis = 9.3 ???? 10 ?￠????10 ). The DOCK1 gene codes for the dedicator of cytokinesis 1 protein, which has a role in myoblast fusion. Conclusions In sum, one statistically significant common variant in the DOCK1 gene was associated with ????BMI in GI cancer and COPD cases providing support for at least partially shared aetiology of ????BMI in complex diseases.
机译：摘要背景已有许多关于癌症恶病质相关性状的候选基因关联研究，但迄今为止尚未发表全基因组关联研究（GWAS）。恶病质表现为具有多种复杂特征的患者，包括癌症和COPD。本研究的目的是通过弗雷明汉心脏研究中的GWAS数据，寻找癌症和COPD中体重指数（BMI）变化的共同遗传病因。方法采用线性混合效应模型，该模型考虑了年龄，性别和吸烟状况的变化，计算了连续三个BMI时间点（n = 4162）的40岁以上参与者的BMI。在1085名癌症诊断参与者，204名胃肠道（GI）癌症，112名肺癌和237名COPD参与者中，使用广义估计方程进行了四个GWAS BMI的测试，以检验其与418365个单核苷酸多态性的相关性（SNP）。结果在COPD病例中，有两个SNP达到了全基因组水平的显着水平（P <5×10×10 8），BMI为：（i）CNTN4基因内的rs41526344。 2 2 ＝ 0.13，P ＝ 4.3 ??? 10 ￠ ??? 8）; （ii）在胃肠道癌病例中的细胞分裂因子1的专用基因（DOCK1）中为rs4751240（2 ＝ 0.10，P ＝1.9≤10≤8≤8）。在COPD病例中，DOCK1 SNP关联在BMI GWAS中复制（2个荟萃分析= 0.10，P个荟萃分析= 9.3×10 = 10 = 10）。 DOCK1基因编码胞质分裂1蛋白的专用因子，该因子在成肌细胞融合中起作用。结论总之，在胃肠癌和COPD病例中，DOCK1基因的一个统计学上显着的共有变异与βBMI有关，这为复杂疾病中βBMI的至少部分病因提供了支持。

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