L-myc和H-ras基因多态性与结直肠癌发病风险的关系

摘要

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.%目的 探讨原癌基因L-myc和H-ras的多态性以及基因-基因交互作用与结直肠癌发病风险的关系.方法 应用病例对照研究,采用聚合酶链反应-限制性片段长度多态性方法检测浙江省嘉善县373例结直肠癌患者和838例健康对照的L-myc、H-ras基因型.采用Mantel-Haenzsel分层分析、叉生分析等统计学方法分析基因-基因交互作用,并采用多因子降维(MDR)模型进行验证.结果 单基因模型显示,L-myc和H-ras的单个基因多态性与结直肠癌的发病风险无关(P＞0.05).分层分析提示,在L-myc LS+ SS基因型携带者中,H-ras TC+ CC基因型携带者相对于TT基因型携带者患直肠癌的风险显著增加(OR=1.81,P=0.005),但不增加结肠癌、结直肠癌的发病风险(均P＞0.05).Logistic回归分析显示,分层后H-ras基因多态性与结肠癌、直肠癌和结直肠癌发病均无关(均P ＞0.05).在携带LL基因型的人群中,以TT基因型为参照,TC+ CC基因型不增加结肠癌、直肠癌和结直肠癌的发病风险(均P ＞0.05).叉生分析结果显示,结肠癌、直肠癌和结直肠癌患者L-myc和H-ras基因的主效应均无统计学意义(均P＞0.05).交互作用分析结果显示,结肠癌和结直肠癌患者中L-myc和H-ras基因不存在交互作用,在直肠癌中存在正相乘模型的交互作用(OR=2.74,P=0.024).MDR模型验证结果显示,L-myc和H-ras在直肠癌中存在基因-基因交互作用,交叉验证一致率为100％ (P =0.001).结论 H-ras和L-myc多态性与结肠癌、直肠癌和结直肠癌发病风险无关,H-ras和L-myc之间的基因-基因交互作用增加直肠癌的发病风险.