调节管腔脂质暴露和结直肠癌风险的功能多态性。
Functional polymorphisms to modulate luminal lipid exposure and risk of colorectal cancer.
机构信息
Karmanos Cancer Institute, Wayne State University School of Medicine, 110 East Warren Avenue, Detroit, MI 48201, USA.
出版信息
Cancer Epidemiol. 2010 Jun;34(3):291-7. doi: 10.1016/j.canep.2010.02.010. Epub 2010 Mar 21.
PURPOSE
Fat absorption may play a crucial role in colorectal carcinogenesis by determining intra-colonic exposure to potentially carcinogenic lipid metabolites.
METHODS
We conducted a population-based case-control study that included 1163 cases and 1501 controls to examine whether individuals who carry genetic variants associated with lower lipid absorption have a higher risk of colorectal cancer. Using Taqman assay, we determined FABP2 alanine (A)/threonine (T) polymorphism at codon 54 in exon-2 and APOE isoforms. Multivariable odds ratios (OR) and 95% confidence intervals (CI) were calculated by unconditional logistic regression models, assuming FABP2 A54 and APO non-E4 as high risk alleles.
RESULTS
We found no associations with either of the polymorphisms. The OR associated with FABP2 A54 homozygotes compared with the others was 1.01 (95% CI; 0.86-1.45) and that for non-ApoE4 carriers compared with carries was 0.95 (95% CI; 0.80-1.13). However, there was a statistically significant negative interaction between total fat intake and FABP2 AA genotypes (p=0.025), indicating that the risk of colorectal cancer associated with this polymorphism is higher in the subjects with lower fat intake.
CONCLUSIONS
These results suggest that these SNPs may not be useful in predicting colorectal cancer risk in populations with high fat intake.
目的
脂肪吸收可能通过决定潜在致癌脂质代谢物在结直肠内的暴露，在结直肠发生癌变中发挥关键作用。
方法
我们进行了一项基于人群的病例对照研究，包括 1163 例病例和 1501 例对照，以研究携带与脂肪吸收降低相关的遗传变异的个体是否具有更高的结直肠癌风险。我们使用 Taqman 检测法，在第 2 外显子的密码子 54 处确定 FABP2 丙氨酸（A）/苏氨酸（T）多态性和 APOE 同工型。采用非条件 logistic 回归模型计算多变量比值比（OR）和 95%置信区间（CI），假设 FABP2 A54 和 APO 非 E4 为高风险等位基因。
结果
我们未发现与这两种多态性相关的关联。与其他等位基因相比，FABP2 A54 纯合子的 OR 为 1.01（95%CI；0.86-1.45），而非 ApoE4 携带者的 OR 为 0.95（95%CI；0.80-1.13）。然而，总脂肪摄入量和 FABP2 AA 基因型之间存在统计学上显著的负交互作用（p=0.025），表明该多态性与结直肠癌的相关性在脂肪摄入量较低的人群中更高。
结论
这些结果表明，在高脂肪摄入量的人群中，这些 SNP 可能无法用于预测结直肠癌的风险。
Zotero 插件