摘要目的 探讨乳腺癌易感基因TOX3基因rs3803662位点单核苷酸多态性与河南汉族女性散发性乳腺癌易感性之间的相关性.方法 选择253例乳腺癌患者和343例乳腺良性病变患者进行病例对照研究,采用imLDR技术对TOX3rs3803662进行单核苷酸多态性(SNP)基因分型,并运用x2检验检测不同基因型在病例组及对照组的分布,并运用非条件logistic回归分析计算比值比(OR)及95％可信区间,评估在不同的遗传模型中不同等位基因型与乳腺癌的发病风险以及与激素受体状态、Ki-67及人表皮生长因子受体2(HER2)基因状态的关联性.结果 TOX3基因rs3803662位点基因型在病例组内以Ki-67、HER2为基础的分组分布差异无统计学意义.在病例组中及对照组之间的分布存在差异,在共显性遗传模型(OR =2.19,95％CI:1.19～4.02)及隐性遗传模型(OR =2.06,95％CI:1.15 ～3.70)中,与等位基因型AA、GA相比,等位基因型GG增加了乳腺癌的患病风险.以雌激素受体状态(ER-status)为基础进行分层分析,在隐性遗传模型机共显性遗传模型中,TOX3rs3803662位点等位基因型GG增加了ER阳性及阴性乳腺癌的发病风险,但在以ER状态为基础的两组亚型中,该SNP与其发病关联性差异无统计学意义.结论 在河南人群中TOX3基因rs3803662位点SNP与河南地区散发性乳腺癌的发病相关,与Ki-67、HER2基因无明显相关性.在共显性遗传及隐性遗传模型中,等位基因型GG增加了河南汉族女性乳腺癌的发病风险,且与不同雌激素受体状态乳腺癌的发病相关.

abstractsObjectives TOX3 gene was considered to be breast cancer susceptibility gene in the European population and East Asian populations.This study was aimed to investigate the relevance of TOX3 gene rs3803662 single nucleotide polymorphisms and sporadic breast cancer susceptibility among the Han Nationality in Henan Province.Methods A case-control study was performed among 253 patients with sporadic breast cancer and 343 control subjects in Henan Province.The SNP rs3803662 in TOX3 was genotyped by imLDR technique.Association analysis based on unconditional logistic regression was carried out to determine the odds ratio (OR) and 95％ confidence interval (95％ CI) for the SNP between different alleles and breast cancer.Results There was no statistically significant difference in the distribution of TOX3 rs3803662 allele in different Ki-67 value and HER2 gene status in the case group.The distribution of TOX3 rs3803662 allele between breast cancer and the control group were different.Compared with allele AA and GA,allele GG increased the risk of breast cancer in codominant inheritance (OR =2.19,95％ CI:1.19-4.02) and recessive genetic models(OR =2.06,95％ CI:1.15-3.70).Further stratifying analysis was conducted based on estrogen receptor status.The SNP rs3803662 showed significant associations with ER status,and was associated with positive ER status in the recessive (OR =1.92;95％ CI:1.00-3.67;P=0.05) and codominant models (OR=2.07;95％CI:1.05-4.08;P=0.036).And this SNP was associated with negative ER status breast cancers in both recessive (OR =2.38;95％ CI:1.10-5.15;P=0.028) and codominant models (OR =2.43;95％ CI:1.08-5.48;P =0.032).But there was no statistically significant difference in each subgroup stratified by ER status.Conclusion This was a verification study in a Han population.In codominant and recessive genetic models,allele GG increased breast cancer risk and was associated with the pathogenesis of different ER status breast cancer.But there was no obvious correlation between this SNP and Ki-67 or HER2 gene.This is the first breast cancer susceptibility loci that is confirmed in Henan population.Our study only analyzes the correlation between the SNP and ER status in breast cancer.More studies and analyses about the association between SNPs and different characteristic of breast cancer should be performed.