TOX3基因-基因、基因-环境交互效应与散发性乳腺癌易感性

The risk of sporadic breast cancer associated with gene - gene, gene - environment interaction in TOX3 gene

目的探讨TOX3基因-基因、基因-环境交互效应在散发性乳腺癌发生中的作用。方法 采用TaqMan单核苷酸多态性（SNP）法检测TOX3基因rs3803662和9302556位点SNPs，采用非条件Logistic回归和MDR法评价基因-基因、基因-环境交互效应、交互效应系数和交互效应最佳模型。结果rs3803662与rs9302556位点变异型基因携带在乳腺癌发生中存在强正交互效应；rs3803662和rs9302556变异型基因与乳腺良性疾病史、口服避孕药等因素在乳腺癌发生中存在交互效应。rs3803662和rs9302556位点变异型基因与行经年限、BMI间的交互效应存在显著的剂量-效应关系（P〈0．05）。携带rs9302556变异型基因、携带rs3803662变异型基因、乳腺良性疾病史、口服避孕药≥1年、吸烟、初潮年龄≤13岁、绝经年龄≥55岁、家族乳腺癌史、BMII≥24．00、月经期≥35年和无哺乳史等11个因子是基因一环境交互效应的最佳模型。结论rs3803662和rs9302556位点变异型基因间存在强正交互效应，基因一环境交互效应在乳腺癌发生中起重要作用。

Objective To investigate the interaction between polymorphism in TOX3 gene and environment factors in sporadic breast cancer. Methods The TaqMan single nucleotide polymorphism （SNP） assay was carried out to detect the dimorphism at the rs3803662 and rs9302556 SNP loci. The risk of sporadic breast cancer with 95% CI was estimated by unconditional logistic regression. The interaction of gene - gene, gene - environment and interaction coefficient was evaluated by unconditional logistic regression. The best interaction model was built by MDR. Results The strong positive interaction was observed between variant genotype of rs3803662 and rs9302556, and between variant genotype of TOX3 and environment factors, such as rs3803662,benign breast disease, oral contraceptives ≥ 1 year and so on. There were a significant dose - response relationship of interaction effects between variant genotype of TOX3 and menstruation years and BMI （ P 〈 0.05 ）. The variant genotypes of rs3803662, rs9302556, benign breast disease, oral contraceptives and other 7 factors were contained in the best interaction model. Conclusion The interaction effects between variant genotype of rs3803662 and rs9302556 loci in TOX3 gene and environment factors play an important role in increased risk of breast cancer.