休闲体育活动改变了常见的GH1基因多态性与结直肠癌风险之间的关联。
Recreational physical activity modifies the association between a common GH1 polymorphism and colorectal cancer risk.
作者信息
Khoury-Shakour Sana, Gruber Stephen B, Lejbkowicz Flavio, Rennert Hedy S, Raskin Leon, Pinchev Mila, Rennert Gad
机构信息
Clalit Health Services National Cancer Control Center, at Carmel Medical Center, Haifa 34362, Israel.
出版信息
Cancer Epidemiol Biomarkers Prev. 2008 Dec;17(12):3314-8. doi: 10.1158/1055-9965.EPI-08-0062.
UNLABELLED
Growth hormone may be associated with the development of colorectal cancer directly and/or indirectly via increased serum level of insulin-like growth factor (IGF-I). Regular physical activity can decrease insulin resistance and modulates IGF-I production. A common polymorphism in the GH1 gene, rs2665802, was previously shown to be associated with lower IGF-I levels and decreased colorectal cancer (CRC) risk. We investigated the association of this polymorphism and physical activity with colorectal cancer risk in a case-control study.
METHODS
The analysis includes 3,041 (1,402 cases and 1,639 controls) participants in the Molecular Epidemiology of Colorectal Cancer study, a population-based case-control study in Northern Israel. Analysis was carried out separately in two sets. The first set included 1,248 subjects (625 cases, 623 controls), and the second validation set consisted of 1,793 subjects (777 cases, 1,016 controls).
RESULTS
No association was found between the studied polymorphism and CRC risk. However, evaluation of gene environment interactions revealed an interaction between leisure time physical activity and the GH1 polymorphism, which was consistent in both sets (P(interaction) = 0.005). The genotype AA was associated with decreased risk of CRC among individuals who did not engage in any such activity (odds ratio, 0.76; 95% confidence interval, 0.52-0.98), whereas the same genotype was marginally associated with increased risk among individuals who reported physical activity (odds ratio, 1.38; 95% confidence interval, 0.98-1.94).
CONCLUSIONS
We found that the A allele of the rs2665802 polymorphism is associated with reduced risk of CRC only among physically inactive individuals, indicating an interaction between physical activity and the growth hormone/IGF-I system. A replication of the observed findings and further investigation of the underlying mechanism is warranted.
未标注
生长激素可能直接和/或通过提高血清胰岛素样生长因子（IGF-I）水平间接与结直肠癌的发生相关。规律的体育活动可降低胰岛素抵抗并调节IGF-I的产生。先前研究表明，GH1基因中的常见多态性rs2665802与较低的IGF-I水平及降低的结直肠癌（CRC）风险相关。我们在一项病例对照研究中调查了这种多态性和体育活动与结直肠癌风险的关联。
方法
分析纳入了3041名参与者（1402例病例和1639例对照），来自以色列北部一项基于人群的结直肠癌分子流行病学病例对照研究。分析在两组中分别进行。第一组包括1248名受试者（625例病例，623例对照），第二验证组由1793名受试者（777例病例，1016例对照）组成。
结果
未发现所研究的多态性与CRC风险之间存在关联。然而，对基因-环境相互作用的评估显示，休闲时间体育活动与GH1多态性之间存在相互作用，两组结果一致（交互作用P = 0.005）。AA基因型与未进行任何此类活动的个体患CRC的风险降低相关（优势比，0.76；95%置信区间，0.52 - 0.98），而相同基因型与报告有体育活动的个体患CRC风险增加略有相关（优势比，1.38；95%置信区间，0.98 - 1.94）。
结论
我们发现rs2665802多态性的A等位基因仅在缺乏体育活动的个体中与CRC风险降低相关，表明体育活动与生长激素/IGF-I系统之间存在相互作用。有必要对观察到的结果进行重复验证并进一步研究潜在机制。
Zotero 插件