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H-ras与L-myc基因多态性与结直肠癌易感性的关联

[Association between H-ras and L-myc gene polymorphisms and susceptibility to colorectal cancer].

作者信息

Ni Qin, Zhang Yong-jing, Zhang Shan-chun, Jin Ming-juan, Ma Xin-yuan, Yao Kai-yan, Li Qi-long, Chen Kun

机构信息

Department of Epidemiology and Health Statistics, Zhejiang University, Hangzhou, China.

出版信息

Zhonghua Zhong Liu Za Zhi. 2012 Jan;34(1):15-20.

Abstract

OBJECTIVE

To explore the association between the polymorphisms of oncogenes H-ras and L-myc and colorectal cancer risk, and the interaction of those genes.

METHODS

The genotypes of H-ras and L-myc genes were determined by polymerase chain reaction-based restriction fragment length polymorphism analysis. Stratified analysis and logistic model were used to detect the gene-gene interaction. The gene-gene interaction was validated by multifactor dimensionality reduction (MDR) analysis.

RESULTS

The single SNP model showed that the polymorphisms of H-ras and L-myc genes were not significantly related with colorectal cancer risk (P > 0.05). Stratified analysis revealed that among the L-myc LS + SS genotype carriers, those with H-ras TC + CC genotype showed significantly increased risk of rectal cancer than those with TT genotype (OR = 1.81, P = 0.005). The positive interaction between L-myc and H-ras was detected by logistic regression model. The OR of the interaction effect was 2.74 (P = 0.024). This result was confirmed in the MDR model, with 54.83% testing balanced accuracy and 10/10 cross-validation consistency, and the model was still significant after the 1000 times permutation test (P = 0.001).

CONCLUSION

Our findings suggest that the polymorphism of H-ras and L-myc genes is not related to colorectal cancer risk, but there is a synergy between H-ras and L-myc polymorphisms in the development of rectal cancer.

摘要

目的

探讨癌基因H-ras和L-myc的多态性与结直肠癌风险之间的关联以及这些基因之间的相互作用。

方法

采用基于聚合酶链反应的限制性片段长度多态性分析来确定H-ras和L-myc基因的基因型。运用分层分析和逻辑模型来检测基因-基因相互作用。通过多因素降维(MDR)分析对基因-基因相互作用进行验证。

结果

单核苷酸多态性(SNP)模型显示,H-ras和L-myc基因的多态性与结直肠癌风险无显著相关性(P>0.05)。分层分析表明,在L-myc LS + SS基因型携带者中,H-ras TC + CC基因型携带者患直肠癌的风险显著高于TT基因型携带者(OR = 1.81,P = 0.005)。通过逻辑回归模型检测到L-myc和H-ras之间存在正向相互作用。相互作用效应的OR为2.74(P = 0.024)。这一结果在MDR模型中得到证实,该模型的测试平衡准确率为54.83%,10/10交叉验证一致性良好,并且在1000次置换检验后该模型仍然具有显著性(P = 0.001)。

结论

我们的研究结果表明,H-ras和L-myc基因的多态性与结直肠癌风险无关,但H-ras和L-myc多态性在直肠癌发生过程中存在协同作用。

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